Angina (Stable)NoTrace-CTONCT07817719
Drug-Coated Balloon Only Strategy After Recanalization of Chronic Total Coronary Occlusions
A study testing Paclitaxel-coated balloon (AGENT Paclitaxel-Coated PTCA Balloon Catheter) and Serial intravascular ultrasound and protocol-mandated nine-month angiographic reassessment in people with Angina (Stable) and Coronary Occlusion, run by University of Sao Paulo General Hospital at 1 site in Brazil.
Trial summary
Chronic total occlusions (CTO) of the coronary arteries are usually treated with drug-eluting stents (DES) after successful recanalization. Permanent metallic scaffolds carry recognized long-term limitations, including late malapposition, very late stent thrombosis, impairment of positive vascular remodeling, and edge… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Angina (Stable), Coronary Occlusion, Coronary Artery Disease
- What is being tested?
- Paclitaxel-coated balloon (AGENT Paclitaxel-Coated PTCA Balloon Catheter) and Serial intravascular ultrasound and protocol-mandated nine-month angiographic reassessment
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteBrazil
- Study dates
- Nov 2026to Jun 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Chronic total coronary occlusion (CTO) of more than three months' duration, confirmed by prior angiography or lesion characteristics
- Clinical indication for revascularization, defined as limiting angina and/or documented ischemia
- Successful CTO recanalization, defined as restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 antegrade flow and absence of any flow-limiting dissection
- Life expectancy greater than one year
- Written informed consent provided
Who cannot join
- Acute coronary syndrome or cardiogenic shock at presentation
- Flow-limiting dissection (TIMI grade below 3) requiring stent implantation
- Left main coronary artery as the CTO target vessel
- Reference vessel diameter below 2.0 mm or above 4.0 mm
- In-stent chronic total occlusion
- Absolute contraindication to dual antiplatelet therapy for the protocol-defined duration of 3 to 6 months
- Inability to achieve adequate lesion preparation, defined as absence of flow-limiting or otherwise significant dissection and satisfactory conditions for drug delivery, confirmed by angiography and intravascular ultrasound (IVUS)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Antonio D Freire, MD, PHD contact
Brazil1 site
InCor - Instituto do Coracao - University of Sao Paulo Heart Institute
São Paulo, São Paulo, 05403-000
Estevao M Pardi, MD, +55 11 2661-5000, estevaopardi@gmail.com
About this study
Official title: NoTrace-CTO: Exclusive Drug-Coated Balloon Use After Recanalization of Chronic Total Coronary Occlusions - A Prospective, Single-Center, Single-Arm Study With Paired Quantitative Coronary Angiography and Serial Intravascular Ultrasound
Chronic total occlusions (CTO) of the coronary arteries are usually treated with drug-eluting stents (DES) after successful recanalization. Permanent metallic scaffolds carry recognized long-term limitations, including late malapposition, very late stent thrombosis, impairment of positive vascular remodeling, and edge restenosis after geographic miss. Drug-coated balloons (DCB) deliver an antiproliferative agent to the vessel wall without leaving a permanent implant, and may be particularly attractive in long, fibrocalcific recanalized CTO segments.
NoTrace-CTO is a prospective, single-center, investigator-initiated, single-arm pilot study evaluating an exclusive DCB-only strategy, with no stent implantation, after successful CTO recanalization. Thirty-eight patients are planned, to yield thirty evaluable patients with paired angiographic follow-up.
Read more
The primary endpoint is in-balloon late lumen loss at nine months, measured by quantitative coronary angiography (QCA) and tested against a pre-specified performance goal of 0.50 mm derived from a pooled contemporary second-generation DES benchmark. The proportion of lesions completing the DCB-only strategy without bailout stenting is reported descriptively alongside it. Serial intravascular ultrasound (IVUS) performed at baseline, immediately after DCB delivery and at nine months is the mechanistic centerpiece of the study, assessing vascular remodeling directly. Secondary assessments include quantitative flow ratio (QFR), Seattle Angina Questionnaire (SAQ) scores, binary restenosis, reocclusion, target lesion and target vessel revascularization, major adverse cardiovascular events (MACE), bleeding classified by the Bleeding Academic Research Consortium (BARC) criteria, and acute kidney injury defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.
The study is not powered for comparative clinical superiority or non-inferiority against DES; its findings are hypothesis-generating and intended to inform the design of an adequately powered multicenter trial.
Read the detailed description
Design:
Prospective, single-center, investigator-initiated, single-arm pilot study conducted at the Heart Institute (InCor), Hospital das Clinicas, University of Sao Paulo Medical School. Consecutive eligible patients are enrolled by convenience sampling from the institutional chronic total occlusion (CTO) recanalization waiting list, following routine care pathways without modification of clinical prioritization or therapeutic decision-making.
Index procedure:
Recanalization follows standard interventional practice under the hybrid CTO algorithm, including antegrade wire escalation, antegrade dissection and re-entry, and retrograde approaches. Baseline lesion complexity is graded with the Multicenter CTO Registry of Japan (J-CTO) and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) scores. Lesion preparation uses sequential semi-compliant and non-compliant balloon predilatation sized approximately 1:1 to the intravascular ultrasound (IVUS) measured reference lumen diameter; cutting or scoring balloons are used at operator discretion where fibrocalcific tissue prevents adequate luminal gain. Drug-coated balloon (DCB) delivery proceeds only after angiographic and IVUS confirmation of adequate lesion preparation, defined as absence of flow-limiting or otherwise significant dissection, and satisfactory conditions for drug delivery.
Device and technique:
The AGENT paclitaxel-coated percutaneous transluminal coronary angioplasty (PTCA) balloon catheter (2 micrograms/mm2 dose density) is sized 1:1 to the IVUS-measured reference vessel diameter, with length selected to cover the full treated segment. Each inflation is maintained for a minimum of 120 seconds at nominal pressure, a pre-specified protocol requirement exceeding the instructions-for-use reference inflation time, adopted to prolong balloon-wall contact in recanalized fibrocalcific segments. Where more than one balloon is required, each inflation independently meets the minimum duration, with at least 2 mm of overlap documented by IVUS. No permanent metallic scaffold is implanted as part of the strategy.
Imaging:
Intravascular ultrasound is acquired with a rotational 60 MHz high-definition system by automated motorized pullback at 0.5 mm/s, extending at least 5 mm beyond each device edge, before and immediately after DCB angioplasty and again at nine months. Serial pullbacks are co-registered using fixed anatomical landmarks. Quantitative coronary angiography (QCA) is performed offline using validated edge-detection software with guiding-catheter calibration and matched angiographic projections between time-points. Analyses are performed by independent readers at the InCor core laboratory blinded to clinical data and time-point; inter- and intra-observer reproducibility are assessed by intraclass correlation coefficient and Bland-Altman limits of agreement, and approximately 10% of paired IVUS studies undergo external over-read by an independent reader unaffiliated with InCor.
Bailout:
If a flow-limiting dissection (Thrombolysis in Myocardial Infarction [TIMI] flow below 3) occurs after DCB dilation and cannot be optimized with repeat inflation, stent implantation is performed. Such cases are classified as technical failure of the DCB-only strategy, count as failures in the DCB-only strategy success proportion, and are retained in the intention-to-treat sensitivity analysis with a pre-specified penalized late lumen loss value rather than being treated as missing.
Antithrombotic therapy:
Dual antiplatelet therapy (DAPT) for 6 months is standard, abbreviated to 3 months in patients at high bleeding risk based on clinical judgment and validated scores.
Follow-up:
Elective angiographic and IVUS reassessment of the target vessel is performed at nine months. Patients declining invasive reassessment may accept coronary computed tomography angiography as a fallback; these patients contribute exploratory descriptive data but not paired QCA or IVUS data to the primary endpoint. Cumulative contrast volume and radiation exposure across both procedures are prospectively tracked.
Analysis populations:
The per-protocol population, comprising enrolled and successfully recanalized lesions that complete the DCB-only strategy without bailout stenting, is the primary analysis population for late lumen loss. The intention-to-treat population is analyzed as a pre-specified, mandatory co-reported sensitivity analysis in which bailout-stented lesions are assigned a penalized late lumen loss value set a priori at 0.50 mm, with rank-based worst-rank imputation additionally reported. DCB-only strategy success is calculated on the full intention-to-treat denominator.
Statistical approach:
Sample size was determined under a one-sample performance-goal framework. The benchmark, derived from a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) aligned pooled analysis of six contemporary second-generation drug-eluting stent (DES) CTO cohorts under independent core-laboratory QCA using a random-effects model with Hartung-Knapp-Sidik-Jonkman adjustment, is a mean in-stent late lumen loss of 0.20 mm with a pooled within-study standard deviation of approximately 0.50 mm. Under a one-sample t-test with one-sided alpha of 0.025 and 90% power, 30 evaluable patients with paired angiographic follow-up are required; allowing approximately 20% attrition, target enrollment is 38. The primary objective is met if the upper bound of the one-sided 97.5% confidence interval for mean in-balloon late lumen loss lies below 0.50 mm. The full type I error is allocated to this single primary endpoint; all other endpoints are supportive or exploratory.
- Being tested
- Paclitaxel-coated balloon (AGENT Paclitaxel-Coated PTCA Balloon Catheter), Serial intravascular ultrasound and protocol-mandated nine-month angiographic reassessment
- Keywords
- Chronic total occlusion, Drug-coated balloon, Paclitaxel, Percutaneous coronary intervention, Late lumen loss, Intravascular ultrasound, Vascular remodeling, Leave nothing behind, Quantitative coronary angiography, Quantitative flow ratio
- Medical subject headings
- Angina, Stable, Coronary Occlusion, Coronary Artery Disease, Vascular Remodeling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paclitaxel-coated balloon (AGENT Paclitaxel-Coated PTCA Balloon Catheter)Device
Also called Drug-coated balloon (DCB), Drug-eluting balloon (DEB)
Paclitaxel-coated balloon at a dose density of 2 micrograms/mm2, sized 1:1 to the intravascular ultrasound (IVUS) measured reference vessel diameter and of sufficient length to cover the full treated segment. Each inflation is maintained for a minimum of 120 seconds at nominal pressure. Where more than one balloon is required for full longitudinal coverage, each inflation independently meets the minimum duration with at least 2 mm of documented overlap.
Serial intravascular ultrasound and protocol-mandated nine-month angiographic reassessmentProcedure or surgery
Intravascular ultrasound with automated motorized pullback at 0.5 mm/s is performed before and immediately after drug-coated balloon angioplasty and repeated at nine months, together with elective diagnostic coronary angiography of the target vessel, to quantify late lumen loss and serial vascular remodeling. Patients declining invasive reassessment may be offered coronary computed tomography angiography as a non-invasive fallback.
| Study group | Role | What they receive |
|---|---|---|
| DCB-only strategy | Experimental | Patients with successful chronic total occlusion (CTO) recanalization and adequate lesion preparation, confirmed by intravascular ultrasound (IVUS) and angiography, receive exclusive paclitaxel drug-coated balloon (DCB) treatment of the target lesion, with no permanent metallic scaffold implanted. Bailout stent implantation is performed only for flow-limiting dissection that cannot be optimized with repeat balloon inflation, and is classified as technical failure of the DCB-only strategy. Receives: Device: Paclitaxel-coated balloon (AGENT Paclitaxel-Coated PTCA Balloon Catheter); Procedure: Serial intravascular ultrasound and protocol-mandated nine-month angiographic reassessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
In-balloon late lumen loss at nine months
Difference between the minimal luminal diameter measured by quantitative coronary angiography immediately after the index procedure and the minimal luminal diameter at nine-month follow-up angiography. This is the sole endpoint against which the pre-specified performance goal of 0.50 mm is formally tested, using the upper bound of the one-sided 97.5% confidence interval, in the per-protocol population.
Measured: 9 months
DCB-only strategy success
Proportion of enrolled, successfully recanalized lesions treated exclusively with a drug-coated balloon without bailout stent implantation, defined consistent with Drug-Coated Balloon Academic Research Consortium recommendations and calculated on the full intention-to-treat denominator. Reported descriptively with an exact Clopper-Pearson 95% confidence interval; not hypothesis-tested against a performance goal.
Measured: Periprocedural
Secondary outcomes (20)
In-segment late lumen loss at nine months
Late lumen loss measured across the analysis segment including the 5 mm proximal and distal margins adjacent to the treated segment, reported as a supportive quantitative coronary angiography measure.
Measured: 9 months
Change in quantitative flow ratio
Quantitative flow ratio (QFR) derived by the frame-count contrast-flow method from at least two angiographic projections separated by 25 degrees or more, with intracoronary nitrate administered before each acquisition, compared between the post-procedural baseline and nine-month follow-up. Exploratory and hypothesis-generating.
Unit of Measure: ratio
Measured: Periprocedural and 9 months
In-balloon binary angiographic restenosis at 9 months
Percent diameter stenosis of 50% or greater within the in-balloon analysis segment at follow-up angiography, defined consistent with Drug-Coated Balloon Academic Research Consortium (DCB-ARC) recommendations and reported as a proportion of lesions with a 95% confidence interval.
Unit of Measure: percentage of lesions
Measured: 9 months
In-segment binary angiographic restenosis at 9 months
Percent diameter stenosis of 50% or greater within the in-segment analysis segment, which includes the 5 mm proximal and distal margins adjacent to the treated segment, at follow-up angiography, defined consistent with Drug-Coated Balloon Academic Research Consortium (DCB-ARC) recommendations and reported as a proportion of lesions with a 95% confidence interval.
Unit of Measure: percentage of lesions
Measured: 9 months
Target lesion reocclusion
Complete occlusion of the target lesion, defined as 100% diameter stenosis with TIMI 0 antegrade flow at follow-up angiography, reported as a proportion with 95% confidence interval.
Measured: 9 months
Clinically driven target lesion revascularization
Any clinically driven repeat revascularization of the target lesion, percutaneous or surgical, reported as a proportion with 95% confidence interval.
Measured: 9 months
Clinically driven target vessel revascularization
Any clinically driven repeat revascularization of the target vessel outside the target lesion, reported as a proportion with 95% confidence interval.
Measured: 9 months
Change in minimal lumen area by intravascular ultrasound
Minimal lumen area within the treated segment measured by IVUS at matched anatomical cross-sections, compared between the immediate post-procedure acquisition and nine-month follow-up.
Measured: Periprocedural and 9 months
Change in external elastic membrane cross-sectional area by intravascular ultrasound
External elastic membrane cross-sectional area measured by intravascular ultrasound (IVUS) at matched anatomical cross-sections within the treated segment, compared between the immediate post-procedure acquisition and nine-month follow-up. Together with the vascular remodeling index this forms the mechanistic centerpiece of the study, testing whether an exclusive drug-coated balloon strategy preserves the vessel's capacity for positive remodeling.
Unit of Measure: square millimeters (mm^2)
Measured: Periprocedural and 9 months
Vascular remodeling index by intravascular ultrasound
Ratio of the external elastic membrane cross-sectional area at nine-month follow-up to the external elastic membrane cross-sectional area immediately after the index procedure, measured by intravascular ultrasound (IVUS) at matched anatomical cross-sections. Values above 1.0 indicate positive remodeling and values below 1.0 indicate negative remodeling.
Unit of Measure: ratio
Measured: Periprocedural and 9 months.
Change in plaque burden by intravascular ultrasound
Plaque plus media cross-sectional area divided by external elastic membrane cross-sectional area, measured by intravascular ultrasound (IVUS) at matched anatomical cross-sections within the treated segment, compared between the immediate post-procedure acquisition and nine-month follow-up. Reported as the absolute change in percentage points.
Unit of Measure: percentage of external elastic membrane area
Measured: Periprocedural and 9 months
Change in percent atheroma volume by intravascular ultrasound
Volumetric percent atheroma volume across the treated segment, calculated as the sum of plaque plus media areas divided by the sum of external elastic membrane areas across all analyzed cross-sections, measured by intravascular ultrasound (IVUS) and compared between the immediate post-procedure acquisition and nine-month follow-up. Reported as the absolute change in percentage points.
Unit of Measure: percentage of total vessel volume
Measured: Periprocedural and 9 months
Change in Seattle Angina Questionnaire Physical Limitation domain score
Change from baseline in the Physical Limitation domain of the Seattle Angina Questionnaire (SAQ), which measures the degree to which angina restricts physical activities. The Seattle Angina Questionnaire is a 19-item disease-specific instrument for coronary artery disease. Each domain is scored from 0 to 100, where 0 is the worst possible and 100 the best possible status; higher scores indicate a better outcome. Change from baseline is reported, so positive values indicate improvement.
Measured: Baseline, 1 month, and 9 months
Change in Seattle Angina Questionnaire Angina Stability domain score
Change from baseline in the Angina Stability domain of the Seattle Angina Questionnaire (SAQ), which measures the change in angina frequency relative to four weeks earlier. The Seattle Angina Questionnaire is a 19-item disease-specific instrument for coronary artery disease. Each domain is scored from 0 to 100, where 0 is the worst possible and 100 the best possible status; higher scores indicate a better outcome. Change from baseline is reported, so positive values indicate improvement.
Measured: Baseline, 1 month, and 9 months
Change in Seattle Angina Questionnaire Angina Frequency domain score
Change from baseline in the Angina Frequency domain of the Seattle Angina Questionnaire (SAQ), which measures how often angina and nitroglycerin use occur. The Seattle Angina Questionnaire is a 19-item disease-specific instrument for coronary artery disease. Each domain is scored from 0 to 100, where 0 is the worst possible and 100 the best possible status; higher scores indicate a better outcome. Change from baseline is reported, so positive values indicate improvement.
Measured: Baseline, 1 month, and 9 months
Change in Seattle Angina Questionnaire Treatment Satisfaction domain score
Change from baseline in the Treatment Satisfaction domain of the Seattle Angina Questionnaire (SAQ), which measures satisfaction with the explanation and management of angina. The Seattle Angina Questionnaire is a 19-item disease-specific instrument for coronary artery disease. Each domain is scored from 0 to 100, where 0 is the worst possible and 100 the best possible status; higher scores indicate a better outcome. Change from baseline is reported, so positive values indicate improvement.
Measured: Baseline, 1 month, and 9 months
Change in Seattle Angina Questionnaire Angina-Related Quality of Life domain score
Change from baseline in the Angina-Related Quality of Life domain of the Seattle Angina Questionnaire (SAQ), which measures the perceived impact of angina on enjoyment of life. The Seattle Angina Questionnaire is a 19-item disease-specific instrument for coronary artery disease. Each domain is scored from 0 to 100, where 0 is the worst possible and 100 the best possible status; higher scores indicate a better outcome. Change from baseline is reported, so positive values indicate improvement.
Measured: Baseline, 1 month, and 9 months
Number of participants with major adverse cardiovascular events
Number of participants experiencing the composite of all-cause death, myocardial infarction, or stroke. Death is classified as cardiovascular or non-cardiovascular where possible; myocardial infarction is defined by the Fourth Universal Definition and includes procedural type 4a and spontaneous events; stroke includes ischemic and hemorrhagic events. The reported value is the number of participants with at least one component event; individual components are reported as separate categories within this measure.
Measured: Up to 9 months
Number of participants with bleeding events by Bleeding Academic Research Consortium type
Number of participants experiencing a bleeding event classified according to Bleeding Academic Research Consortium (BARC) criteria. The reported value is the number of participants with any BARC type 1 through 5 bleeding event; events are reported as separate categories for major bleeding (BARC type 3 or 5), clinically relevant non-major bleeding (BARC type 2), and minor bleeding (BARC type 1).
Measured: Up to 9 months
Number of participants with acute kidney injury
Number of participants developing acute kidney injury as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, assessed after the index procedure and after the nine-month follow-up angiography. Cumulative contrast volume across both procedures is recorded.
Measured: Periprocedural
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2026
- Study startNov 2026 (estimated)
- Primary completionFeb 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Angina (Stable)Studies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-arm pilot study; all enrolled patients receive an exclusive drug-coated balloon strategy after successful chronic total occlusion recanalization, with no stent implantation unless bailout is required.
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Boston Scientific Corporation
- Responsible party
- Sponsor
- Investigators
- Antonio D Freire, MD, PhD, Principal investigator, University of Sao Paulo Heart Institute - InCor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07817719
- Sponsor's protocol ID
- 96316426.6.0000.0068
- Acronym
- NoTrace-CTO
- Status last verified
- Aug 2026
- First submitted
- 1 Sep 2026
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the results reported in the primary publication will be made available, together with the data dictionary, the statistical analysis plan, and the study protocol. Angiographic and intravascular ultrasound source images will not be shared, as they cannot be reliably de-identified within the constraints of the institutional data protection policy; derived quantitative measurements from those images will be included in the shared dataset.
Publications
Jeger RV, Eccleshall S, Wan Ahmad WA, Ge J, Poerner TC, Shin ES, Alfonso F, Latib A, Ong PJ, Rissanen TT, Saucedo J, Scheller B, Kleber FX; International DCB Consensus Group. Drug-Coated Balloons for Coronary Artery Disease: Third Report of the International DCB Consensus Group. JACC Cardiovasc Interv. 2020 Jun 22;13(12):1391-1402. doi: 10.1016/j.jcin.2020.02.043. Epub 2020 May 27.
PubMed 32473887Mutlu D, Rempakos A, Strepkos D, Carvalho PEP, Alexandrou M, Kladou E, Ser OS, Azzalini L, Jaffer FA, Ybarra L, Goktekin O, Uluganyan M, Ozdemir R, Elbarouni B, Alaswad K, Davies R, ElGuindy A, Kocas C, Sural S, Poommipanit P, Frizzel J, Basir MB, Raj L, Young L, Rangan BV, Mastrodemos OC, Sara JDS, Jalli S, Sandoval Y, Burke MN, Brilakis ES, Gorgulu S. Drug-Coated Balloons in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the PROGRESS-CTO Registry. Catheter Cardiovasc Interv. 2025 Dec;106(7):3783-3795. doi: 10.1002/ccd.70240. Epub 2025 Oct 13.
PubMed 41084138Fezzi S, Scheller B, Cortese B, Alfonso F, Jeger R, Colombo A, Joner M, Shin ES, Kleber FX, Latib A, Rissanen TT, Eccleshall S, Ribichini F, Tao L, Koo BK, Chieffo A, Ge J, Granada JF, Stoll HP, Spaulding C, Cavalcante R, Abizaid A, Muramatsu T, Boudoulas KD, Waksman R, Mehran R, Cutlip DE, Krucoff MW, Stone GW, Garg S, Onuma Y, Serruys PW. Definitions and standardized endpoints for the use of drug-coated balloon in coronary artery disease: consensus document of the Drug Coated Balloon Academic Research Consortium. Eur Heart J. 2025 Jul 7;46(26):2498-2519. doi: 10.1093/eurheartj/ehaf029.
PubMed 40270117Brilakis ES, Mashayekhi K, Tsuchikane E, Abi Rafeh N, Alaswad K, Araya M, Avran A, Azzalini L, Babunashvili AM, Bayani B, Bhindi R, Boudou N, Boukhris M, Bozinovic NZ, Bryniarski L, Bufe A, Buller CE, Burke MN, Buttner HJ, Cardoso P, Carlino M, Christiansen EH, Colombo A, Croce K, Damas de Los Santos F, De Martini T, Dens J, Di Mario C, Dou K, Egred M, ElGuindy AM, Escaned J, Furkalo S, Gagnor A, Galassi AR, Garbo R, Ge J, Goel PK, Goktekin O, Grancini L, Grantham JA, Hanratty C, Harb S, Harding SA, Henriques JPS, Hill JM, Jaffer FA, Jang Y, Jussila R, Kalnins A, Kalyanasundaram A, Kandzari DE, Kao HL, Karmpaliotis D, Kassem HH, Knaapen P, Kornowski R, Krestyaninov O, Kumar AVG, Laanmets P, Lamelas P, Lee SW, Lefevre T, Li Y, Lim ST, Lo S, Lombardi W, McEntegart M, Munawar M, Navarro Lecaro JA, Ngo HM, Nicholson W, Olivecrona GK, Padilla L, Postu M, Quadros A, Quesada FH, Prakasa Rao VS, Reifart N, Saghatelyan M, Santiago R, Sianos G, Smith E, C Spratt J, Stone GW, Strange JW, Tammam K, Ungi I, Vo M, Vu VH, Walsh S, Werner GS, Wollmuth JR, Wu EB, Wyman RM, Xu B, Yamane M, Ybarra LF, Yeh RW, Zhang Q, Rinfret S. Guiding Principles for Chronic Total Occlusion Percutaneous Coronary Intervention. Circulation. 2019 Jul 30;140(5):420-433. doi: 10.1161/CIRCULATIONAHA.119.039797. Epub 2019 Jul 29.
PubMed 31356129
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NoTrace-CTO: Exclusive Drug-Coated Balloon Use After Recanalization of Chronic Total Coronary Occlusions - A Prospective, Single-Center, Single-Arm Study With Paired Quantitative Coronary Angiography and Serial Intravascular Ultrasound
- ClinicalTrials.gov ID
- NCT07817719
- Acronym / sponsor ID
- NoTrace-CTO / 96316426.6.0000.0068
- Keywords
- Chronic total occlusion, Drug-coated balloon, Paclitaxel, Percutaneous coronary intervention, Late lumen loss, Intravascular ultrasound, Vascular remodeling, Leave nothing behind
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Collaborators
- Boston Scientific Corporation
- Study start
- Nov 2026 (estimated)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 14 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic total occlusions (CTO) of the coronary arteries are usually treated with drug-eluting stents (DES) after successful recanalization. Permanent metallic scaffolds carry recognized long-term limitations, including late malapposition, very late stent thrombosis, impairment of positive vascular remodeling, and edge restenosis after geographic miss. Drug-coated balloons (DCB) deliver an antiproliferative agent to the vessel wall without leaving a permanent implant, and may be particularly attractive in long, fibrocalcific recanalized CTO segments.
NoTrace-CTO is a prospective, single-center, investigator-initiated, single-arm pilot study evaluating an exclusive DCB-only strategy, with no stent implantation, after successful CTO recanalization. Thirty-eight patients are planned, to yield thirty evaluable patients with paired angiographic follow-up.
The primary endpoint is in-balloon late lumen loss at nine months, measured by quantitative coronary angiography (QCA) and tested against a pre-specified performance goal of 0.50 mm derived from a pooled contemporary second-generation DES benchmark. The proportion of lesions completing the DCB-only strategy without bailout stenting is reported descriptively alongside it. Serial intravascular ultrasound (IVUS) performed at baseline, immediately after DCB delivery and at nine months is the mechanistic centerpiece of the study, assessing vascular remodeling directly. Secondary assessments include quantitative flow ratio (QFR), Seattle Angina Questionnaire (SAQ) scores, binary restenosis, reocclusion, target lesion and target vessel revascularization, major adverse cardiovascular events (MACE), bleeding classified by the Bleeding Academic Research Consortium (BARC) criteria, and acute kidney injury defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.
The study is not powered for comparative clinical superiority or non-inferiority against DES; its findings are hypothesis-generating and intended to inform the design of an adequately powered multicenter trial.
Detailed description
Design:
Prospective, single-center, investigator-initiated, single-arm pilot study conducted at the Heart Institute (InCor), Hospital das Clinicas, University of Sao Paulo Medical School. Consecutive eligible patients are enrolled by convenience sampling from the institutional chronic total occlusion (CTO) recanalization waiting list, following routine care pathways without modification of clinical prioritization or therapeutic decision-making.
Index procedure:
Recanalization follows standard interventional practice under the hybrid CTO algorithm, including antegrade wire escalation, antegrade dissection and re-entry, and retrograde approaches. Baseline lesion complexity is graded with the Multicenter CTO Registry of Japan (J-CTO) and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) scores. Lesion preparation uses sequential semi-compliant and non-compliant balloon predilatation sized approximately 1:1 to the intravascular ultrasound (IVUS) measured reference lumen diameter; cutting or scoring balloons are used at operator discretion where fibrocalcific tissue prevents adequate luminal gain. Drug-coated balloon (DCB) delivery proceeds only after angiographic and IVUS confirmation of adequate lesion preparation, defined as absence of flow-limiting or otherwise significant dissection, and satisfactory conditions for drug delivery.
Device and technique:
The AGENT paclitaxel-coated percutaneous transluminal coronary angioplasty (PTCA) balloon catheter (2 micrograms/mm2 dose density) is sized 1:1 to the IVUS-measured reference vessel diameter, with length selected to cover the full treated segment. Each inflation is maintained for a minimum of 120 seconds at nominal pressure, a pre-specified protocol requirement exceeding the instructions-for-use reference inflation time, adopted to prolong balloon-wall contact in recanalized fibrocalcific segments. Where more than one balloon is required, each inflation independently meets the minimum duration, with at least 2 mm of overlap documented by IVUS. No permanent metallic scaffold is implanted as part of the strategy.
Imaging:
Intravascular ultrasound is acquired with a rotational 60 MHz high-definition system by automated motorized pullback at 0.5 mm/s, extending at least 5 mm beyond each device edge, before and immediately after DCB angioplasty and again at nine months. Serial pullbacks are co-registered using fixed anatomical landmarks. Quantitative coronary angiography (QCA) is performed offline using validated edge-detection software with guiding-catheter calibration and matched angiographic projections between time-points. Analyses are performed by independent readers at the InCor core laboratory blinded to clinical data and time-point; inter- and intra-observer reproducibility are assessed by intraclass correlation coefficient and Bland-Altman limits of agreement, and approximately 10% of paired IVUS studies undergo external over-read by an independent reader unaffiliated with InCor.
Bailout:
If a flow-limiting dissection (Thrombolysis in Myocardial Infarction [TIMI] flow below 3) occurs after DCB dilation and cannot be optimized with repeat inflation, stent implantation is performed. Such cases are classified as technical failure of the DCB-only strategy, count as failures in the DCB-only strategy success proportion, and are retained in the intention-to-treat sensitivity analysis with a pre-specified penalized late lumen loss value rather than being treated as missing.
Antithrombotic therapy:
Dual antiplatelet therapy (DAPT) for 6 months is standard, abbreviated to 3 months in patients at high bleeding risk based on clinical judgment and validated scores.
Follow-up:
Elective angiographic and IVUS reassessment of the target vessel is performed at nine months. Patients declining invasive reassessment may accept coronary computed tomography angiography as a fallback; these patients contribute exploratory descriptive data but not paired QCA or IVUS data to the primary endpoint. Cumulative contrast volume and radiation exposure across both procedures are prospectively tracked.
Analysis populations:
The per-protocol population, comprising enrolled and successfully recanalized lesions that complete the DCB-only strategy without bailout stenting, is the primary analysis population for late lumen loss. The intention-to-treat population is analyzed as a pre-specified, mandatory co-reported sensitivity analysis in which bailout-stented lesions are assigned a penalized late lumen loss value set a priori at 0.50 mm, with rank-based worst-rank imputation additionally reported. DCB-only strategy success is calculated on the full intention-to-treat denominator.
Statistical approach:
Sample size was determined under a one-sample performance-goal framework. The benchmark, derived from a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) aligned pooled analysis of six contemporary second-generation drug-eluting stent (DES) CTO cohorts under independent core-laboratory QCA using a random-effects model with Hartung-Knapp-Sidik-Jonkman adjustment, is a mean in-stent late lumen loss of 0.20 mm with a pooled within-study standard deviation of approximately 0.50 mm. Under a one-sample t-test with one-sided alpha of 0.025 and 90% power, 30 evaluable patients with paired angiographic follow-up are required; allowing approximately 20% attrition, target enrollment is 38. The primary objective is met if the upper bound of the one-sided 97.5% confidence interval for mean in-balloon late lumen loss lies below 0.50 mm. The full type I error is allocated to this single primary endpoint; all other endpoints are supportive or exploratory.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-arm pilot study; all enrolled patients receive an exclusive drug-coated balloon strategy after successful chronic total occlusion recanalization, with no stent implantation unless bailout is required.
| Arm | Type | Receives |
|---|---|---|
| DCB-only strategy | Experimental | Device: Paclitaxel-coated balloon (AGENT Paclitaxel-Coated PTCA Balloon Catheter), Procedure: Serial intravascular ultrasound and protocol-mandated nine-month angiographic reassessmentPatients with successful chronic total occlusion (CTO) recanalization and adequate lesion preparation, confirmed by intravascular ultrasound (IVUS) and angiography, receive exclusive paclitaxel drug-coated balloon (DCB) treatment of the target lesion, with no permanent metallic scaffold implanted. Bailout stent implantation is performed only for flow-limiting dissection that cannot be optimized with repeat balloon inflation, and is classified as technical failure of the DCB-only strategy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18 years or older
- Chronic total coronary occlusion (CTO) of more than three months' duration, confirmed by prior angiography or lesion characteristics
- Clinical indication for revascularization, defined as limiting angina and/or documented ischemia
- Successful CTO recanalization, defined as restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 antegrade flow and absence of any flow-limiting dissection
- Life expectancy greater than one year
Key exclusion criteria (7 listed)
- Acute coronary syndrome or cardiogenic shock at presentation
- Flow-limiting dissection (TIMI grade below 3) requiring stent implantation
- Left main coronary artery as the CTO target vessel
- Reference vessel diameter below 2.0 mm or above 4.0 mm
- In-stent chronic total occlusion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Paclitaxel-coated balloon (AGENT Paclitaxel-Coated PTCA Balloon Catheter)Also: Drug-coated balloon (DCB), Drug-eluting balloon (DEB)Paclitaxel-coated balloon at a dose density of 2 micrograms/mm2, sized 1:1 to the intravascular ultrasound (IVUS) measured reference vessel diameter and of sufficient length to cover the full treated segment. Each inflation is maintained for a minimum of 120 seconds at nominal pressure. Where more than one balloon is required for full longitudinal coverage, each inflation independently meets the minimum duration with at least 2 mm of documented overlap. | Device | DCB-only strategy |
| Serial intravascular ultrasound and protocol-mandated nine-month angiographic reassessmentIntravascular ultrasound with automated motorized pullback at 0.5 mm/s is performed before and immediately after drug-coated balloon angioplasty and repeated at nine months, together with elective diagnostic coronary angiography of the target vessel, to quantify late lumen loss and serial vascular remodeling. Patients declining invasive reassessment may be offered coronary computed tomography angiography as a non-invasive fallback. | Procedure or surgery | DCB-only strategy |
Primary outcome
In-balloon late lumen loss at nine months
Time frame: 9 months
Difference between the minimal luminal diameter measured by quantitative coronary angiography immediately after the index procedure and the minimal luminal diameter at nine-month follow-up angiography. This is the sole endpoint against which the pre-specified performance goal of 0.50 mm is formally tested, using the upper bound of the one-sided 97.5% confidence interval, in the per-protocol population.
DCB-only strategy success
Time frame: Periprocedural
Proportion of enrolled, successfully recanalized lesions treated exclusively with a drug-coated balloon without bailout stent implantation, defined consistent with Drug-Coated Balloon Academic Research Consortium recommendations and calculated on the full intention-to-treat denominator. Reported descriptively with an exact Clopper-Pearson 95% confidence interval; not hypothesis-tested against a performance goal.
20 secondary outcomes
In-segment late lumen loss at nine months
Time frame: 9 months
Change in quantitative flow ratio
Time frame: Periprocedural and 9 months
In-balloon binary angiographic restenosis at 9 months
Time frame: 9 months
In-segment binary angiographic restenosis at 9 months
Time frame: 9 months
Target lesion reocclusion
Time frame: 9 months
Clinically driven target lesion revascularization
Time frame: 9 months
Clinically driven target vessel revascularization
Time frame: 9 months
Change in minimal lumen area by intravascular ultrasound
Time frame: Periprocedural and 9 months
Change in external elastic membrane cross-sectional area by intravascular ultrasound
Time frame: Periprocedural and 9 months
Vascular remodeling index by intravascular ultrasound
Time frame: Periprocedural and 9 months.
Change in plaque burden by intravascular ultrasound
Time frame: Periprocedural and 9 months
Change in percent atheroma volume by intravascular ultrasound
Time frame: Periprocedural and 9 months
Change in Seattle Angina Questionnaire Physical Limitation domain score
Time frame: Baseline, 1 month, and 9 months
Change in Seattle Angina Questionnaire Angina Stability domain score
Time frame: Baseline, 1 month, and 9 months
Change in Seattle Angina Questionnaire Angina Frequency domain score
Time frame: Baseline, 1 month, and 9 months
Change in Seattle Angina Questionnaire Treatment Satisfaction domain score
Time frame: Baseline, 1 month, and 9 months
Change in Seattle Angina Questionnaire Angina-Related Quality of Life domain score
Time frame: Baseline, 1 month, and 9 months
Number of participants with major adverse cardiovascular events
Time frame: Up to 9 months
Number of participants with bleeding events by Bleeding Academic Research Consortium type
Time frame: Up to 9 months
Number of participants with acute kidney injury
Time frame: Periprocedural
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Background: PubMed 32473887Jeger RV, Eccleshall S, Wan Ahmad WA, Ge J, Poerner TC, Shin ES, Alfonso F, Latib A, Ong PJ, Rissanen TT, Saucedo J, Scheller B, Kleber FX; International DCB Consensus Group. Drug-Coated Balloons for Coronary Artery Disease: Third Report of the International DCB Consensus Group. JACC Cardiovasc Interv. 2020 Jun 22;13(12):1391-1402. doi: 10.1016/j.jcin.2020.02.043. Epub 2020 May 27.
- Background: PubMed 41084138Mutlu D, Rempakos A, Strepkos D, Carvalho PEP, Alexandrou M, Kladou E, Ser OS, Azzalini L, Jaffer FA, Ybarra L, Goktekin O, Uluganyan M, Ozdemir R, Elbarouni B, Alaswad K, Davies R, ElGuindy A, Kocas C, Sural S, Poommipanit P, Frizzel J, Basir MB, Raj L, Young L, Rangan BV, Mastrodemos OC, Sara JDS, Jalli S, Sandoval Y, Burke MN, Brilakis ES, Gorgulu S. Drug-Coated Balloons in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the PROGRESS-CTO Registry. Catheter Cardiovasc Interv. 2025 Dec;106(7):3783-3795. doi: 10.1002/ccd.70240. Epub 2025 Oct 13.
- Background: PubMed 40270117Fezzi S, Scheller B, Cortese B, Alfonso F, Jeger R, Colombo A, Joner M, Shin ES, Kleber FX, Latib A, Rissanen TT, Eccleshall S, Ribichini F, Tao L, Koo BK, Chieffo A, Ge J, Granada JF, Stoll HP, Spaulding C, Cavalcante R, Abizaid A, Muramatsu T, Boudoulas KD, Waksman R, Mehran R, Cutlip DE, Krucoff MW, Stone GW, Garg S, Onuma Y, Serruys PW. Definitions and standardized endpoints for the use of drug-coated balloon in coronary artery disease: consensus document of the Drug Coated Balloon Academic Research Consortium. Eur Heart J. 2025 Jul 7;46(26):2498-2519. doi: 10.1093/eurheartj/ehaf029.
- Background: PubMed 31356129Brilakis ES, Mashayekhi K, Tsuchikane E, Abi Rafeh N, Alaswad K, Araya M, Avran A, Azzalini L, Babunashvili AM, Bayani B, Bhindi R, Boudou N, Boukhris M, Bozinovic NZ, Bryniarski L, Bufe A, Buller CE, Burke MN, Buttner HJ, Cardoso P, Carlino M, Christiansen EH, Colombo A, Croce K, Damas de Los Santos F, De Martini T, Dens J, Di Mario C, Dou K, Egred M, ElGuindy AM, Escaned J, Furkalo S, Gagnor A, Galassi AR, Garbo R, Ge J, Goel PK, Goktekin O, Grancini L, Grantham JA, Hanratty C, Harb S, Harding SA, Henriques JPS, Hill JM, Jaffer FA, Jang Y, Jussila R, Kalnins A, Kalyanasundaram A, Kandzari DE, Kao HL, Karmpaliotis D, Kassem HH, Knaapen P, Kornowski R, Krestyaninov O, Kumar AVG, Laanmets P, Lamelas P, Lee SW, Lefevre T, Li Y, Lim ST, Lo S, Lombardi W, McEntegart M, Munawar M, Navarro Lecaro JA, Ngo HM, Nicholson W, Olivecrona GK, Padilla L, Postu M, Quadros A, Quesada FH, Prakasa Rao VS, Reifart N, Saghatelyan M, Santiago R, Sianos G, Smith E, C Spratt J, Stone GW, Strange JW, Tammam K, Ungi I, Vo M, Vu VH, Walsh S, Werner GS, Wollmuth JR, Wu EB, Wyman RM, Xu B, Yamane M, Ybarra LF, Yeh RW, Zhang Q, Rinfret S. Guiding Principles for Chronic Total Occlusion Percutaneous Coronary Intervention. Circulation. 2019 Jul 30;140(5):420-433. doi: 10.1161/CIRCULATIONAHA.119.039797. Epub 2019 Jul 29.
- Individual participant dataSharing planned: Yes. De-identified individual participant data underlying the results reported in the primary publication will be made available, together with the data dictionary, the statistical analysis plan, and the study protocol. Angiographic and intravascular ultrasound source images will not be shared, as they cannot be reliably de-identified within the constraints of the institutional data protection policy; derived quantitative measurements from those images will be included in the shared dataset.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Antonio D Freire, MD, PHD contact
Antonio D Freire, MD, PhD principal investigator
University of Sao Paulo Heart Institute - InCor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Paclitaxel-coated balloon (AGENT Paclitaxel-Coated PTCA Balloon Catheter) and Serial intravascular ultrasound and protocol-mandated nine-month angiographic reassessment in people with Angina (Stable) and Coronary Occlusion, run by University of Sao Paulo General Hospital at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Estevao M Pardi, MD (+55 11 964863553, estevaopardi@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
In-balloon late lumen loss at nine months (time frame: 9 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07817719, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.