Coronary Artery DiseaseREFORMNCT04079192
Biolimus A9™ (BA9™) Drug Coated Balloon (DCB) Study
A study testing Biolimus A9 Drug Coated Balloon and SeQuent Please Paclitaxel Drug Coated Balloon in people with Coronary Artery Disease and In-Stent Restenosis, run by Biosensors Europe SA at 15 sites in 5 countries.
Trial summary
The study is a Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the BA9™ Drug Coated Balloon for the Treatment of In-Stent Restenosis. It is a First-in-Man Trial. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Coronary Artery Disease, In-Stent Restenosis
- What is being tested?
- Biolimus A9 Drug Coated Balloon and SeQuent Please Paclitaxel Drug Coated Balloon
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 201 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 7 Aug 2020to Apr 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients presenting with in-stent restenosis (ISR) and clinical symptoms of ischemia and/or (i) evidence of ischemia on non-invasive testing or (ii) hemodynamically relevant lesion defined by FFR ≤ 0.80 or iFR ≤ 0.89 or > 90% stenosis.
- Patient presenting with a lesion that can be fully covered with one DCB length. - Patients can have up to two index lesions with ISR, which can both be treated and evaluated.
- Patient has provided written informed consent
- Age ≥ 18 years.
- Patient is willing and able to comply with the study procedures and follow-up.
Who cannot join
- Patient presents with a ST-elevation myocardial infarction (STEMI) or had an acute MI within 48 hours prior to presentation (according to the universal definition of myocardial infarction).
- Patient with acute cardiac decompensation or acute cardiogenic shock
- Documented left ventricular ejection fraction (LVEF) ≤ 30%
- Patient with impaired renal function (glomerular filtration rate < 80 mL/min/1.73 m2).
- More than 2 epicardial vessels requiring revascularization
- Significant left main stenosis (by visual estimation) or an ISR located in the left main (LM).
Show all 15Show fewer
- Patient has an ISR lesion that cannot be covered with one DCB length.
- Patient has an ISR in the target segment in a stent of a smaller diameter than 2.5mm.
- Severe calcification that might prevent a sufficient expansion of the DCB, if not pre-treated with rotablation or a shockwave application device.
- Known hypersensitivity or contraindication to biolimus, paclitaxcel, aspirin, thienopyridines, or iodinated contrast that cannot be pre-treated.
- Pregnant and/or breast-feeding females or females who intend to become pregnant during the time of the study.
- Subject currently enrolled in other investigational device or drug trial in which the primary endpoint has not yet been reached.
- Anticipated difficulties to complete the angiographic follow-up study.
- Patient with a life expectancy of less than 12 months.
- Patients lacking mental capacity (i.e. patients suffering from dementia and others) to provide informed consent.
Trial locations and contacts
15 sites in 5 countries.
15 sites in 5 countries
United Kingdom6 sites
Royal Bournemouth hospital
Bournemouth
University Hospital of Wales
Cardiff
Craigavon Cardiac Centre
Craigavon
Dorset County Hospital
Dorchester
Altnagelvin Area Hospital
Londonderry
Worcestershire Royal Hospital
Worcester
Germany3 sites
Heart Center, Segeberger Kliniken
Bad Segeberg
Heart Center Leipzig - University of Leipzig
Leipzig
Evangelisches Krankenhaus Paul Gerhardt Stift
Wittenberg
Spain3 sites
Hospital Clinic de Barcelona
Barcelona
Hospital Clinico San Carlos
Madrid
Hospital Universitario de La Princesa
Madrid
About this study
Official title: A Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the BA9TM Drug Coated Balloon for the Treatment of In-Stent Restenosis: First-in-Man Trial (REFORM)
The study is a Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the BA9™ Drug Coated Balloon for the Treatment of In-Stent Restenosis. It is a First-in-Man Trial.
Read the detailed description
This clinical trial will serve as a first-in-human (FIH) experience for the BA9™ DCB in a population of patients with coronary artery disease who have an indication for interventional treatment of in-stent restenosis (ISR) in a bare-metal stent (BMS) or drug-eluting stent (DES).
The study uses a prospective, multi-center, single blind, randomized controlled trial design to enroll 195 patients. The study will seek to prove that the BA9-DCB is non-inferior to the approved CE marked Sequent Please® Paclitaxel Coated Balloon with respect to % Diameter Stenosis and has similar safety characteristics.
- Conditions
- Coronary Artery Disease, In-Stent Restenosis
- Being tested
- Biolimus A9 Drug Coated Balloon, SeQuent Please Paclitaxel Drug Coated Balloon
- Keywords
- Drug-Coated Balloon
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biolimus A9 Drug Coated BalloonDevice
A non-surgical procedure that uses a catheter to place a semi-compliant angioplasty drug coated balloon to open up coronary arteries that have been narrowed by atherosclerosis. The balloon is inflated to treat the stenosis and transfer the drug to arterial wall, and then is deflated and withdrawn.
SeQuent Please Paclitaxel Drug Coated BalloonDevice
A non-surgical procedure that uses a catheter to place a semi-compliant angioplasty drug coated balloon to open up coronary arteries that have been narrowed by atherosclerosis. The balloon is inflated to treat the stenosis and transfer the drug to arterial wall, and then is deflated and withdrawn.
| Study group | Role | What they receive |
|---|---|---|
| Biolimus A9™ Drug Coated Balloon | Experimental | Patients who meet the eligibility criteria and who are randomised to this arm, will receive treatment with the Biolimus A9™ Drug Coated Balloon Receives: Device: Biolimus A9 Drug Coated Balloon |
| Sequent ® Please Paclitaxel coated balloon | Active comparator | Patients who meet the eligibility criteria and who are randomised to this arm, will receive treatment with the Sequent ® Please Paclitaxel coated balloon Receives: Device: SeQuent Please Paclitaxel Drug Coated Balloon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Diameter Stenosis (DS)
Percent DS of the target segment assessed by quantitative coronary angiography (QCA)
Measured: 6 months
Secondary outcomes (2)
Target lesion failure
Taget lesion failure defined as a composite of cardiovascular death, any target vessel myocardial infarction, coronary artery bypass graft and clinically driven target lesion revascularization
Measured: 1 month, 6 months, 1 year and 2 years
Target vessel failure
Target vessel failure defined as a composite of cardiovascular death, any target vessel myocardial infarction, and clinically driven target vessel revascularization
Measured: 1 month, 6 months, 1 year and 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2019
- Study start7 Aug 2020
- Primary completionApr 2023 (estimated)
- Study completionApr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients who meet all the eligibility criteria will be randomized 2:1 to receive treatment with either a BA9-DCB or a Sequent Please® Paclitaxel Coated Balloon.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 201 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biosensors Europe SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert A Byrne, MD, PhD, Principal investigator, Mater Private Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04079192
- Sponsor's protocol ID
- 19-EU-01
- Acronym
- REFORM
- Status last verified
- Aug 2022
- First submitted
- 27 Aug 2019
- Last updated
- 10 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
O'Callaghan D, Coughlan JJ, Alfonso F, Hahn JY, Sabate M, Toelg R, Copt S, Fitzgerald S, Morice MC, Trevelyan J, Mylotte D, Ortiz AF, Durand R, Wohrle J, Kleber FX, Stefanini G, Rai H, O'Kane P, Byrne RA. Final 2-Year Results of the REFORM Study: A Randomized Trial of Biolimus DCB Versus Paclitaxel DCB for In-Stent Restenosis. Catheter Cardiovasc Interv. 2026 Aug 17. doi: 10.1002/ccd.70800. Online ahead of print.
PubMed 42605897Byrne RA, Hahn JY, O'Kane P, Sabate M, Toelg R, Copt S, Fitzgerald S, Morice MC, Trevelyan J, Mylotte D, Ortiz AF, Rai H, Durand R, Wohrle J, Kleber FX, Stefanini G, Alfonso F. Randomized Trial of Biolimus DCB for In-Stent Restenosis: The Primary Results of the REFORM Study. JACC Cardiovasc Interv. 2025 Mar 10;18(5):654-662. doi: 10.1016/j.jcin.2024.11.026. Epub 2025 Feb 5.
PubMed 39918494Traynor BP, Fitzgerald S, Alfonso F, O'Kane P, Sabate M, Tolg R, Trevelyan J, Hahn JY, Mylotte D, Wohrle J, Rai H, Cortese B, Morice MC, Schuette D, Copt S, Oldroyd KG, Byrne RA; REFORM investigators. Design and rationale of a prospective, randomized, non-inferiority trial to determine the safety and efficacy of the Biolimus A9 drug coated balloon for the treatment of in-stent restenosis: First-in-man trial (REFORM). Cardiovasc Revasc Med. 2023 Nov;56:75-81. doi: 10.1016/j.carrev.2023.06.004. Epub 2023 Jun 6.
PubMed 37328392
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the BA9TM Drug Coated Balloon for the Treatment of In-Stent Restenosis: First-in-Man Trial (REFORM)
- ClinicalTrials.gov ID
- NCT04079192
- Acronym / sponsor ID
- REFORM / 19-EU-01
- Conditions
- Coronary Artery Disease, In-Stent Restenosis
- Keywords
- Drug-Coated Balloon
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 201 participants (actual)
- Lead sponsor
- Biosensors Europe SAIndustry (pharma, biotech, devices)
- Study start
- 7 Aug 2020 (actual)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Apr 2024 (estimated)
- First posted
- 6 Sep 2019 (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.
The study is a Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the BA9™ Drug Coated Balloon for the Treatment of In-Stent Restenosis. It is a First-in-Man Trial.
Detailed description
This clinical trial will serve as a first-in-human (FIH) experience for the BA9™ DCB in a population of patients with coronary artery disease who have an indication for interventional treatment of in-stent restenosis (ISR) in a bare-metal stent (BMS) or drug-eluting stent (DES).
The study uses a prospective, multi-center, single blind, randomized controlled trial design to enroll 195 patients. The study will seek to prove that the BA9-DCB is non-inferior to the approved CE marked Sequent Please® Paclitaxel Coated Balloon with respect to % Diameter Stenosis and has similar safety characteristics.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Patients who meet all the eligibility criteria will be randomized 2:1 to receive treatment with either a BA9-DCB or a Sequent Please® Paclitaxel Coated Balloon.
| Arm | Type | Receives |
|---|---|---|
| Biolimus A9™ Drug Coated Balloon | Experimental | Device: Biolimus A9 Drug Coated BalloonPatients who meet the eligibility criteria and who are randomised to this arm, will receive treatment with the Biolimus A9™ Drug Coated Balloon |
| Sequent ® Please Paclitaxel coated balloon | Active comparator | Device: SeQuent Please Paclitaxel Drug Coated BalloonPatients who meet the eligibility criteria and who are randomised to this arm, will receive treatment with the Sequent ® Please Paclitaxel coated balloon |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients presenting with in-stent restenosis (ISR) and clinical symptoms of ischemia and/or (i) evidence of ischemia on non-invasive testing or (ii) hemodynamically relevant lesion defined by FFR ≤ 0.80 or iFR ≤ 0.89 or > 90% stenosis.
- Patient presenting with a lesion that can be fully covered with one DCB length. - Patients can have up to two index lesions with ISR, which can both be treated and evaluated.
- Patient has provided written informed consent
- Age ≥ 18 years.
- Patient is willing and able to comply with the study procedures and follow-up.
Key exclusion criteria (15 listed)
- Patient presents with a ST-elevation myocardial infarction (STEMI) or had an acute MI within 48 hours prior to presentation (according to the universal definition of myocardial infarction).
- Patient with acute cardiac decompensation or acute cardiogenic shock
- Documented left ventricular ejection fraction (LVEF) ≤ 30%
- Patient with impaired renal function (glomerular filtration rate < 80 mL/min/1.73 m2).
- More than 2 epicardial vessels requiring revascularization
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 |
|---|---|---|
| Biolimus A9 Drug Coated BalloonA non-surgical procedure that uses a catheter to place a semi-compliant angioplasty drug coated balloon to open up coronary arteries that have been narrowed by atherosclerosis. The balloon is inflated to treat the stenosis and transfer the drug to arterial wall, and then is deflated and withdrawn. | Device | Biolimus A9™ Drug Coated Balloon |
| SeQuent Please Paclitaxel Drug Coated BalloonA non-surgical procedure that uses a catheter to place a semi-compliant angioplasty drug coated balloon to open up coronary arteries that have been narrowed by atherosclerosis. The balloon is inflated to treat the stenosis and transfer the drug to arterial wall, and then is deflated and withdrawn. | Device | Sequent ® Please Paclitaxel coated balloon |
Primary outcome
Percent Diameter Stenosis (DS)
Time frame: 6 months
Percent DS of the target segment assessed by quantitative coronary angiography (QCA)
2 secondary outcomes
Target lesion failure
Time frame: 1 month, 6 months, 1 year and 2 years
Target vessel failure
Time frame: 1 month, 6 months, 1 year and 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2022.
- Derived from this study: PubMed 42605897O'Callaghan D, Coughlan JJ, Alfonso F, Hahn JY, Sabate M, Toelg R, Copt S, Fitzgerald S, Morice MC, Trevelyan J, Mylotte D, Ortiz AF, Durand R, Wohrle J, Kleber FX, Stefanini G, Rai H, O'Kane P, Byrne RA. Final 2-Year Results of the REFORM Study: A Randomized Trial of Biolimus DCB Versus Paclitaxel DCB for In-Stent Restenosis. Catheter Cardiovasc Interv. 2026 Aug 17. doi: 10.1002/ccd.70800. Online ahead of print.
- Derived from this study: PubMed 39918494Byrne RA, Hahn JY, O'Kane P, Sabate M, Toelg R, Copt S, Fitzgerald S, Morice MC, Trevelyan J, Mylotte D, Ortiz AF, Rai H, Durand R, Wohrle J, Kleber FX, Stefanini G, Alfonso F. Randomized Trial of Biolimus DCB for In-Stent Restenosis: The Primary Results of the REFORM Study. JACC Cardiovasc Interv. 2025 Mar 10;18(5):654-662. doi: 10.1016/j.jcin.2024.11.026. Epub 2025 Feb 5.
- Derived from this study: PubMed 37328392Traynor BP, Fitzgerald S, Alfonso F, O'Kane P, Sabate M, Tolg R, Trevelyan J, Hahn JY, Mylotte D, Wohrle J, Rai H, Cortese B, Morice MC, Schuette D, Copt S, Oldroyd KG, Byrne RA; REFORM investigators. Design and rationale of a prospective, randomized, non-inferiority trial to determine the safety and efficacy of the Biolimus A9 drug coated balloon for the treatment of in-stent restenosis: First-in-man trial (REFORM). Cardiovasc Revasc Med. 2023 Nov;56:75-81. doi: 10.1016/j.carrev.2023.06.004. Epub 2023 Jun 6.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Robert A Byrne, MD, PhD principal investigator
Mater Private Hospital
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Biolimus A9 Drug Coated Balloon and SeQuent Please Paclitaxel Drug Coated Balloon in people with Coronary Artery Disease and In-Stent Restenosis, run by Biosensors Europe SA at 15 sites in 5 countries.
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 5 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 10 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United Kingdom, Germany, Spain, Ireland, Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Diameter Stenosis (DS) (time frame: 6 months). 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 NCT04079192, which also lists 3 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 10 Aug 2022.