Pulmonary EmbolismPhase 3CANARYNCT05172115
Catheter-Directed Thrombolysis Versus Anticoagulation Monotherapy in Intermediate-High Risk PE
A Phase 3 study testing Conventional catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rtPA) and Enoxaparin in people with Pulmonary Embolism and Pulmonary Thromboembolisms, run by Rajaie Cardiovascular Medical and Research Center at 1 site in Iran.
Trial summary
In an open-label parallel groups blinded-endpoint randomized clinical trial, the investigators aim to assess the safety and efficacy of conventional catheter-directed thrombolysis (CDT) vs anticoagulation monotherapy on outcomes of patients with acute intermediate-high risk pulmonary embolism. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Embolism, Pulmonary Thromboembolisms, Embolism, Pulmonary
- What is being tested?
- Conventional catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rtPA) and Enoxaparin
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 1 siteIran
- Study dates
- 22 Dec 2018to 2 May 2020
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥18 years
- Confirmed acute pulmonary emboli by computed tomography pulmonary angiography (CTPA)
- Symptom onset ≤14 day
- Elevated N-terminal-proB-type natriuretic peptide and cardiac troponin
- Right ventricle/left ventricle ratio >0.9 in transthoracic echocardiography
- Less than 48 hours of anticoagulation therapy
- Willingness for participation in the study with signed and dated informed consent form
Who cannot join
- Pulmonary emboli detected by modalities other than CTPA
- Segmental PE
- High risk (massive)
- Severe renal dysfunction(creatinine clearance [CrCl] below 30 mL/min)
- Terminal illness Surgery within 2 weeks
- Platelet count <50.000 /µL
Show all 11Show fewer
- Pre and post catheter directed thrombolysis echocardiography exam not possible
- Contraindication to thrombolytic therapy
- Concomitant right heart thrombi
- Allergic reaction to study medications
- Lack or withdrawal of informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Catheter-Directed Thrombolysis Versus ANticoagulation Monotherapy in Patients With Acute Intermediate-High Risk PulmonarY Embolism: The CANARY Randomized Clinical Trial
In an open-label parallel groups blinded-endpoint randomized clinical trial, the investigators aim to assess the safety and efficacy of conventional catheter-directed thrombolysis (CDT) vs anticoagulation monotherapy on outcomes of patients with acute intermediate-high risk pulmonary embolism. The investigators hypothesize that CDT will have a superior efficacy and safety compared with anticoagulation-only therapy regarding the proportion of patients with a right ventricle to left ventricle (RV/LV) ratio > 0.9 at a 3-month follow-up by an imaging core laboratory, major bleeding, severe thrombocytopenia, or vascular access complication.
Read the detailed description
Treatment of intermediate risk PE is still debated. Despite the promising results of small studies on the efficacy and safety of systemic thrombolytic therapy, larger trials failed to show a net clinical benefit. Pulmonary EmbolIsmTHrOmbolysis (PEITHO) trial which compared the full-dose systemic thrombolysis (i.e., tenecteplase) versus anticoagulation therapy in patients with intermediate-risk PE showed significant lower incidence of mortality or hemodynamic collapse in the first 7 days after randomization in patients who received tenecteplase (2.6% vs 5.6% in placebo group, [odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P value, 0.02]). However the mortality benefit was neutralized by the increased risk of major bleeding in thrombolytic arm (11.5% vs 2.4% in the tenecteplase and placebo group, respectively. Importantly, during the long-term follow up (median of 37.8 months) of PEITHO participants, the thrombolytic therapy failed to improve the RV right ventricular function, residual dyspnea ( 36% in thrombolysis group vs 30.1% in the placebo group), or mortality rates (20.3% in thrombolysis group vs 18 % in the placebo group ). CTEPH occurred in ( 2.1% in thrombolysis group vs 3.2% in the placebo group. The lack of benefit of full-dose thrombolytic in PEITHO, might have several explanations. Intermediate risk PE compose of heterogenous group of patients with different prognosis in whom one fits all approach would not be applicable. This heterogeneity in prognosis were underlined in the latest guideline of the European Society of Cardiology (ESC) which classified the intermediate-risk PE category into two groups of intermediate-low and intermediate-high risk patients according to the right ventricle function and cardiac biomarker levels. Second, lower-dose thrombolytic regimen might result in the same benefit with lower bleeding events. CDT, by delivering drug locally, claims to increase the efficacy of thrombolytic agents and consequently decrease the required dose which might translate to lower bleeding events.
In an open-label parallel groups blinded-endpoint randomized clinical trial, we aim to evaluate the safety and efficacy of standard catheter-directed thrombolysis (CDT) vs anticoagulation-only therapy in patients with acute intermediate-high risk pulmonary embolism. The hypothesis is that CDT will have a superior efficacy and safety regarding the proportion of patients with a RV/LV ratio > 0.9 at a 3-month follow-up assessed by an imaging core laboratory with the lower complications of major bleeding, severe thrombocytopenia, and vascular access complication.
- Conditions
- Pulmonary Embolism, Pulmonary Thromboembolisms, Embolism, Pulmonary, Right Ventricular Dysfunction
- Being tested
- Conventional catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rtPA), Enoxaparin
- Keywords
- Intermediate-high risk pulmonary embolism, Catheter-directed thrombolysis, Anticoagulation
- Medical subject headings
- Pulmonary Embolism, Ventricular Dysfunction, Right
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conventional catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rtPA)Procedure or surgery
Also called Cragg-McNamara™ valved infusion catheters
Conventional catheter-directed thrombolysis with fixed-dose of 24 mg tissue plasminogen activator infusion over 24 hours
EnoxaparinDrug
Also called low molecular weight heparin (LMWH)
Subcutaneous enoxaparin twice-daily (1mg/kg)
| Study group | Role | What they receive |
|---|---|---|
| Conventional catheter-directed thrombolysis (CDT) | Experimental | Conventional catheter-directed thrombolysis (CDT) will be the interventional arm. CDT will be administered using fixed-dose of 24 mg tissue plasminogen activator infusion over 24 hours (0.5 mg/h per catheter if bilateral or 1 mg/h per unilateral catheter) with 500 unit per hour of infusion of unfractionated heparin during the thrombolytic therapy. The therapeutic dose of heparin will immediately be substituted the CDT after termination, and twice-daily subcutaneous enoxaparin (1mg/kg) for the first 48 hours after the thrombolytic therapy will be administered. Direct oral anticoagulation will be in ones with no clinical deterioration. Receives: Procedure: Conventional catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rtPA) |
| Anticoagulation-only therapy | Active comparator | The anticoagulation-only therapy will be the assigned treatment in the control arm. Control patients will receive subcutaneous enoxaparin (twice-daily, 1mg/kg) in the first 48hours of enrollment. Direct oral anticoagulation will be in ones with no clinical deterioration. Receives: Drug: Enoxaparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients with a RV/LV ratio >0.9
Proportion of patients with a RV/LV ratio >0.9 at a assessed by an imaging core laboratory 3-month follow-up
Measured: At 3 months from randomization
Secondary outcomes (6)
The proportion of patients with an RV/LV ratio >0.9
A composite of the proportion of patients with a RV/LV ratio >0.9 at a assessed by an imaging core laboratory 72 hours follow-up
Measured: At 72 hours from randomization
The proportion of patients with Unrecovered RV
The PEITHO definition for RV recovery was employed, as follows: 1) RV size (at the mid-cavity level In apical 4-chamber view) <35 mm, 2) pulmonary artery pressure <35 mm Hg, 3) an RV/LV ratio <0.9, and 4) the normalization of RV free wall motion. The fulfillment of all the criteria, some criteria, and none of the criteria was defined as complete, partial, and no recovery, respectively.
Measured: At 3 months from randomization
All-cause mortality
Survival status of the patient (being alive or dead) at the end of 3 months follow up
Measured: Within 3-month Study period
Major bleeding
According to the Bleeding Academic Research Consortium (BARC 3 or 5 bleeding)
Measured: Within 3-month Study period
Severe thrombocytopenia
Platelet count <20.000/µL
Measured: Within 3-month Study period
Vascular access complication
Major vascular access complication
Measured: Within 3-month Study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2021
- Study start22 Dec 2018
- Primary completion2 Feb 2020
- Study completion2 May 2020
Why it stopped: Due to the COVID-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary EmbolismStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 open-label parallel group randomized controlled trial with concealed allocation sequence and blinded outcome adjudication
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rajaie Cardiovascular Medical and Research Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Parham Sadeghipour, Rajaie Cardiovascular Medical and Research Center
- Investigators
- Parham Sadeghipour, M.D, Principal investigator, Rajaie Cardiovascular Medical and Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05172115
- Sponsor's protocol ID
- 97056
- Acronym
- CANARY
- Status last verified
- Dec 2021
- First submitted
- 10 Dec 2021
- Last updated
- 29 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will become available to interested investigators upon submitting a reasonable research request, approved by the Steering Committee of the trial.
Publications
Sadeghipour P, Jenab Y, Moosavi J, Hosseini K, Mohebbi B, Hosseinsabet A, Chatterjee S, Pouraliakbar H, Shirani S, Shishehbor MH, Alizadehasl A, Farrashi M, Rezvani MA, Rafiee F, Jalali A, Rashedi S, Shafe O, Giri J, Monreal M, Jimenez D, Lang I, Maleki M, Goldhaber SZ, Krumholz HM, Piazza G, Bikdeli B. Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High-risk Pulmonary Embolism: The CANARY Randomized Clinical Trial. JAMA Cardiol. 2022 Dec 1;7(12):1189-1197. doi: 10.1001/jamacardio.2022.3591.
PubMed 36260302
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Catheter-Directed Thrombolysis Versus ANticoagulation Monotherapy in Patients With Acute Intermediate-High Risk PulmonarY Embolism: The CANARY Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05172115
- Acronym / sponsor ID
- CANARY / 97056
- Conditions
- Pulmonary Embolism, Pulmonary Thromboembolisms, Embolism, Pulmonary, Right Ventricular Dysfunction
- Keywords
- Intermediate-high risk pulmonary embolism, Catheter-directed thrombolysis, Anticoagulation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to the COVID-19 pandemic
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Rajaie Cardiovascular Medical and Research CenterUniversity, hospital or other
- Study start
- 22 Dec 2018 (actual)
- Primary completion
- 2 Feb 2020 (actual)
- Study completion
- 2 May 2020 (actual)
- First posted
- 29 Dec 2021 (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.
In an open-label parallel groups blinded-endpoint randomized clinical trial, the investigators aim to assess the safety and efficacy of conventional catheter-directed thrombolysis (CDT) vs anticoagulation monotherapy on outcomes of patients with acute intermediate-high risk pulmonary embolism. The investigators hypothesize that CDT will have a superior efficacy and safety compared with anticoagulation-only therapy regarding the proportion of patients with a right ventricle to left ventricle (RV/LV) ratio > 0.9 at a 3-month follow-up by an imaging core laboratory, major bleeding, severe thrombocytopenia, or vascular access complication.
Detailed description
Treatment of intermediate risk PE is still debated. Despite the promising results of small studies on the efficacy and safety of systemic thrombolytic therapy, larger trials failed to show a net clinical benefit. Pulmonary EmbolIsmTHrOmbolysis (PEITHO) trial which compared the full-dose systemic thrombolysis (i.e., tenecteplase) versus anticoagulation therapy in patients with intermediate-risk PE showed significant lower incidence of mortality or hemodynamic collapse in the first 7 days after randomization in patients who received tenecteplase (2.6% vs 5.6% in placebo group, [odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P value, 0.02]). However the mortality benefit was neutralized by the increased risk of major bleeding in thrombolytic arm (11.5% vs 2.4% in the tenecteplase and placebo group, respectively. Importantly, during the long-term follow up (median of 37.8 months) of PEITHO participants, the thrombolytic therapy failed to improve the RV right ventricular function, residual dyspnea ( 36% in thrombolysis group vs 30.1% in the placebo group), or mortality rates (20.3% in thrombolysis group vs 18 % in the placebo group ). CTEPH occurred in ( 2.1% in thrombolysis group vs 3.2% in the placebo group. The lack of benefit of full-dose thrombolytic in PEITHO, might have several explanations. Intermediate risk PE compose of heterogenous group of patients with different prognosis in whom one fits all approach would not be applicable. This heterogeneity in prognosis were underlined in the latest guideline of the European Society of Cardiology (ESC) which classified the intermediate-risk PE category into two groups of intermediate-low and intermediate-high risk patients according to the right ventricle function and cardiac biomarker levels. Second, lower-dose thrombolytic regimen might result in the same benefit with lower bleeding events. CDT, by delivering drug locally, claims to increase the efficacy of thrombolytic agents and consequently decrease the required dose which might translate to lower bleeding events.
In an open-label parallel groups blinded-endpoint randomized clinical trial, we aim to evaluate the safety and efficacy of standard catheter-directed thrombolysis (CDT) vs anticoagulation-only therapy in patients with acute intermediate-high risk pulmonary embolism. The hypothesis is that CDT will have a superior efficacy and safety regarding the proportion of patients with a RV/LV ratio > 0.9 at a 3-month follow-up assessed by an imaging core laboratory with the lower complications of major bleeding, severe thrombocytopenia, and vascular access complication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- 1:1 open-label parallel group randomized controlled trial with concealed allocation sequence and blinded outcome adjudication
| Arm | Type | Receives |
|---|---|---|
| Conventional catheter-directed thrombolysis (CDT) | Experimental | Procedure: Conventional catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rtPA)Conventional catheter-directed thrombolysis (CDT) will be the interventional arm. CDT will be administered using fixed-dose of 24 mg tissue plasminogen activator infusion over 24 hours (0.5 mg/h per catheter if bilateral or 1 mg/h per unilateral catheter) with 500 unit per hour of infusion of unfractionated heparin during the thrombolytic therapy. The therapeutic dose of heparin will immediately be substituted the CDT after termination, and twice-daily subcutaneous enoxaparin (1mg/kg) for the first 48 hours after the thrombolytic therapy will be administered. Direct oral anticoagulation will be in ones with no clinical deterioration. |
| Anticoagulation-only therapy | Active comparator | Drug: EnoxaparinThe anticoagulation-only therapy will be the assigned treatment in the control arm. Control patients will receive subcutaneous enoxaparin (twice-daily, 1mg/kg) in the first 48hours of enrollment. Direct oral anticoagulation will be in ones with no clinical deterioration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients ≥18 years
- Confirmed acute pulmonary emboli by computed tomography pulmonary angiography (CTPA)
- Symptom onset ≤14 day
- Elevated N-terminal-proB-type natriuretic peptide and cardiac troponin
- Right ventricle/left ventricle ratio >0.9 in transthoracic echocardiography
Key exclusion criteria (11 listed)
- Pulmonary emboli detected by modalities other than CTPA
- Segmental PE
- High risk (massive)
- Severe renal dysfunction(creatinine clearance [CrCl] below 30 mL/min)
- Terminal illness Surgery within 2 weeks
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 |
|---|---|---|
| Conventional catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rtPA)Also: Cragg-McNamara™ valved infusion cathetersConventional catheter-directed thrombolysis with fixed-dose of 24 mg tissue plasminogen activator infusion over 24 hours | Procedure or surgery | Conventional catheter-directed thrombolysis (CDT) |
| EnoxaparinAlso: low molecular weight heparin (LMWH)Subcutaneous enoxaparin twice-daily (1mg/kg) | Drug | Anticoagulation-only therapy |
Primary outcome
The proportion of patients with a RV/LV ratio >0.9
Time frame: At 3 months from randomization
Proportion of patients with a RV/LV ratio >0.9 at a assessed by an imaging core laboratory 3-month follow-up
6 secondary outcomes
The proportion of patients with an RV/LV ratio >0.9
Time frame: At 72 hours from randomization
The proportion of patients with Unrecovered RV
Time frame: At 3 months from randomization
All-cause mortality
Time frame: Within 3-month Study period
Major bleeding
Time frame: Within 3-month Study period
Severe thrombocytopenia
Time frame: Within 3-month Study period
Vascular access complication
Time frame: Within 3-month Study period
Results and safety
The study was stopped early (reason given: Due to the COVID-19 pandemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2021.
- Derived from this study: PubMed 36260302Sadeghipour P, Jenab Y, Moosavi J, Hosseini K, Mohebbi B, Hosseinsabet A, Chatterjee S, Pouraliakbar H, Shirani S, Shishehbor MH, Alizadehasl A, Farrashi M, Rezvani MA, Rafiee F, Jalali A, Rashedi S, Shafe O, Giri J, Monreal M, Jimenez D, Lang I, Maleki M, Goldhaber SZ, Krumholz HM, Piazza G, Bikdeli B. Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High-risk Pulmonary Embolism: The CANARY Randomized Clinical Trial. JAMA Cardiol. 2022 Dec 1;7(12):1189-1197. doi: 10.1001/jamacardio.2022.3591.
- Individual participant dataSharing planned: No. Data will become available to interested investigators upon submitting a reasonable research request, approved by the Steering Committee of the trial.
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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.
Parham Sadeghipour, M.D principal investigator
Rajaie Cardiovascular Medical and Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Conventional catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rtPA) and Enoxaparin in people with Pulmonary Embolism and Pulmonary Thromboembolisms, run by Rajaie Cardiovascular Medical and Research Center at 1 site in Iran.
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 7 inclusion and 11 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: stopped early, as of the sponsor's last update on 29 Dec 2021. 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 Iran. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to the COVID-19 pandemic). 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?
The proportion of patients with a RV/LV ratio >0.9 (time frame: At 3 months from randomization). 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 NCT05172115, which also lists 1 linked publication.
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 29 Dec 2021.