Chronic Total OcclusionsPhase 1NCT01271335
Collagenase Total Occlusion-1 Trial
A Phase 1 study testing collagenase in people with Chronic Total Occlusions, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
A prospective, three-center, phase I safety and tolerability dose escalation study, evaluating 28 subjects in 4 discrete dose cohorts of acute intracoronary injected collagenase ranging from 300 - 1200 µg prior to routine standard-of-care percutaneous revascularization procedures in subjects with chronic total… Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Chronic Total Occlusions
- What is being tested?
- collagenase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2009to Feb 2012
- Phase
- Phase 1
- 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 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Candidates for this study must meet ALL of the following inclusion criteria:
- Subject is willing and able to provide an informed consent
- Subject is willing and able to comply with the study procedures and follow-up
- Subject is 35 years of age or older
- Women who are non-reproductive, or reproductive women who are willing and able to practice effective birth control methods. A urine pregnancy test should be done at the screening/Day0 on all reproductive women of child bearing ability
- Subjects with CTO (older than 6 weeks or unknown duration based on the investigator's assessment of appropriateness for the study) with a clinical indication for revascularization. In subjects with occlusions of unknown duration, there must be absence of any identifiable ischemic event in the 6 weeks prior to enrolment in the study
- At least 1 previously failed attempt to cross the CTO
- Absence of pericardial effusion on 2D Echocardiogram
Who cannot join
- Candidates for this study who meet any of the following criteria at the time of the screening visit are NOT eligible to be enrolled in this study:
- Culprit vessel is a saphenous vein graft occlusion
- True ostial LAD, LCX or RCA occlusions (since collagenase delivery will be unreliable)
- Presence of moderate or large pericardial effusion on echocardiogram within 2 weeks of the procedure
- Major side branch (1.5 mm diameter) within 3 mm proximal to the occlusion. (This is to prevent the infusate being diverted through a side branch and to prevent ischemia during the prolonged period of time during the infusion)
- Renal dysfunction (creatinine greater than 2 x ULN)
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- Severe calcification (collagenase can not degrade calcium) based on consensus of 2 interventional cardiologists after review of coronary angiogram.
- Subject has any medical condition, which in the judgment of the Investigator and/or designee makes the subject a poor candidate for the investigational procedure
- Subject is a pregnant or lactating female (women of childbearing potential must have a negative serum beta-HCG within 24 hours prior to the inclusion)
- Subject is or has been partaking in another investigational product clinical study within 30 days of Screening/Day0
- Subjects with bleeding abnormalities (e.g. Factor VIII deficiency) and /or subjects that have experienced any medically documented active site of bleeding within 30 days of the screening visit, such as, but not limited to, the gastrointestinal or genitourinary tract or intercerebral hemorrhage.
- Subjects with recent acute coronary syndrome (ACS) (< 4 weeks). For those patients who had ACS ≥ 4weeks ago, only the non-culprit vessel from the recent ACS can be considered eligible for this study if all other inclusion and exclusion criteria have been met.
Trial locations and contacts
1 site in 1 country.
About this study
A prospective, three-center, phase I safety and tolerability dose escalation study, evaluating 28 subjects in 4 discrete dose cohorts of acute intracoronary injected collagenase ranging from 300 - 1200 µg prior to routine standard-of-care percutaneous revascularization procedures in subjects with chronic total coronary artery occlusions (CTOs).
Read the detailed description
Enrolment is expected to occur over 24 months with total study duration of approximately 30 months. Five (5) subjects will be enrolled into each dose cohort. The dose cohorts will be studied in a sequential fashion, starting with the lowest doses and escalating to the highest doses. It is anticipated that each subject's involvement with the study will be 3.5 months. In addition, eight (8) subjects will be included in the highest dose cohort to collect pharmacokinetic plasma samples.
Subject enrollment and dosing within each dose cohort will be staged such that the next subsequent subject will not be dosed until the previous subject has been successfully discharged from the hospital after the angioplasty attempt. At a minimum there will be 3 days in between each subject dosing to ensure product safety.
There will be no advancement to the higher dose cohort until all 5 subjects have been discharged from the hospital and a safety review is conducted by the Data Safety Monitoring Board (DSMB) on the cardiac safety measures and the treatment deemed safe to proceed to the next dosing level.
A total of 28 male and / or female subjects suffering from CAD with a CTO will be enrolled into the study at three sites (Sunnybrook Health Sciences Centre and St. Michael's Hospital, Toronto, Ontario, and and Laval Hospital Research Centre, Quebec City, Quebec,Canada). All subjects will have had one or more previous failed angioplasty attempt(s) of the occluded artery. Subjects who have signed an Informed Consent Form (ICF) and meeting all inclusion criteria and having none of the exclusion criteria at Visit 1 (Screening) will be included in the study. All potentially enrollable subjects at Sunnybrook will be reviewed by either of two cardiologist not involved in the study to discuss the available options for the subject and to approve enrollment decisions. Eligible subjects that agree to participate will be treated in a two part procedure. On Day0 using standard angioplasty techniques to access the specified occluded coronary artery, Collagenase (MZ-004) will be directly injected into the occluded artery through a microcatheter that has been positioned immediately adjacent to or into the proximal cap of the occlusion. The catheters and arterial sheath will then be removed and the subject will be monitored overnight on the ward. The following day (Day1), the subject will be brought back to the catheterization laboratory and undergo an angioplasty using standard angioplasty techniques. Routine post-procedural management will then be followed. The subject will be discharged on Day2 in the absence of any cardiac complications (such as elevated cardiac enzymes or large pericardial effusion as judged by the Investigator and determined by echocardiography). Prior to the angioplasty procedure on Day1 and again on Day2 prior to discharge, the subject will undergo an echocardiogram to determine the presence and severity of a pericardial effusion. A moderate or large pericardial effusion or any sign of tamponade on Day1 will be a contraindication to performing the procedure, and the subject will be terminated from the study. A telephone follow-up will be performed 30 days post Day1 in all subjects who have signed an ICF and been enrolled in the study. At 3 months, subjects will undergo an outpatient coronary Computer Tomography (CT) angiogram to ensure there are no delayed effects on the treated vessel (e.g. aneurysm formation), the myocardium or the pericardium.
The primary objective is to evaluate the safety and tolerability of acute intracoronary doses of collagenase (MZ-004) in symptomatic subjects with coronary CTO.
The secondary objective is to obtain preliminary efficacy information of guidewire crossing with increasing doses of intracoronary collagenase in subjects with previously failed at least one previous attempt in coronary CTO.
- Conditions
- Chronic Total Occlusions
- Being tested
- collagenase
- Keywords
- CTO, Angioplasty, PCI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
collagenaseBiological
Also called MZ-004
Lyophilized powder / sterile dosage form for single local intravascular administration via the occluded coronary.
| Study group | Role | What they receive |
|---|---|---|
| Collagenase (MZ-004) | Experimental | Local intra-coronary administration of MZ-004 at or into the CTO Receives: Biological: collagenase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
- Major Adverse Cardiac events, AE and SAE.
- Cardiac enzymes, hematology and biochemistry; changes between Screening relative to Days 1 \& 30.
- Vital Signs
- A 2D-echocardiogram examination will be done on Day1 (18-24 hours after the collagenase administration prior to the CTO crossing procedure) and again on Day2 prior to discharge.
Measured: At 3 months
Secondary outcomes (2)
Efficacy
The efficacy endpoint of this study is guidewire crossing success rates in CTOs. A response rate of 30% or greater at a particular dose will support further clinical testing of MZ-004.
Measured: Day 2
Pharmacokinetic
Subjects in the highest dose cohort, who are participating in the PK sub-study, will have blood draws taken post dose to prior to the PCI attempt on Day2. The blood draws will coincide with standard of care blood draws, whenever possible.
5 ml of blood will be drawn into a serum tube at each PK timepoint. All PK samples will be stored at -80 °C until the end of the study and analyzed together.
Measured: PK blood draws will be assessed at 15, 30, 60, 120, 240, 480 min. and 18 hrs post removal of microcatheter
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2011 (estimated)
- Study startNov 2009
- Primary completionSep 2011
- Study completionFeb 2012
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 Chronic Total OcclusionsStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Bradley Strauss, Sunnybrook Health Sciences Centre
- Investigators
- Bradley Strauss, MD, PhD, FRCP(C), Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01271335
- Sponsor's protocol ID
- CTO-1
- Other IDs
- CIHR
- Status last verified
- Mar 2012
- First submitted
- 5 Jan 2011
- Last updated
- 23 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Strauss BH, Osherov AB, Radhakrishnan S, Mancini GB, Manners A, Sparkes JD, Chisholm RJ. Collagenase Total Occlusion-1 (CTO-1) trial: a phase I, dose-escalation, safety study. Circulation. 2012 Jan 24;125(3):522-8. doi: 10.1161/CIRCULATIONAHA.111.063198. Epub 2011 Dec 16.
PubMed 22179536
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Collagenase Total Occlusion-1 Trial
- ClinicalTrials.gov ID
- NCT01271335
- Acronym / sponsor ID
- CTO-1
- Conditions
- Chronic Total Occlusions
- Keywords
- CTO, Angioplasty, PCI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- Nov 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 6 Jan 2011 (estimated)
- 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.
A prospective, three-center, phase I safety and tolerability dose escalation study, evaluating 28 subjects in 4 discrete dose cohorts of acute intracoronary injected collagenase ranging from 300 - 1200 µg prior to routine standard-of-care percutaneous revascularization procedures in subjects with chronic total coronary artery occlusions (CTOs).
Detailed description
Enrolment is expected to occur over 24 months with total study duration of approximately 30 months. Five (5) subjects will be enrolled into each dose cohort. The dose cohorts will be studied in a sequential fashion, starting with the lowest doses and escalating to the highest doses. It is anticipated that each subject's involvement with the study will be 3.5 months. In addition, eight (8) subjects will be included in the highest dose cohort to collect pharmacokinetic plasma samples.
Subject enrollment and dosing within each dose cohort will be staged such that the next subsequent subject will not be dosed until the previous subject has been successfully discharged from the hospital after the angioplasty attempt. At a minimum there will be 3 days in between each subject dosing to ensure product safety.
There will be no advancement to the higher dose cohort until all 5 subjects have been discharged from the hospital and a safety review is conducted by the Data Safety Monitoring Board (DSMB) on the cardiac safety measures and the treatment deemed safe to proceed to the next dosing level.
A total of 28 male and / or female subjects suffering from CAD with a CTO will be enrolled into the study at three sites (Sunnybrook Health Sciences Centre and St. Michael's Hospital, Toronto, Ontario, and and Laval Hospital Research Centre, Quebec City, Quebec,Canada). All subjects will have had one or more previous failed angioplasty attempt(s) of the occluded artery. Subjects who have signed an Informed Consent Form (ICF) and meeting all inclusion criteria and having none of the exclusion criteria at Visit 1 (Screening) will be included in the study. All potentially enrollable subjects at Sunnybrook will be reviewed by either of two cardiologist not involved in the study to discuss the available options for the subject and to approve enrollment decisions. Eligible subjects that agree to participate will be treated in a two part procedure. On Day0 using standard angioplasty techniques to access the specified occluded coronary artery, Collagenase (MZ-004) will be directly injected into the occluded artery through a microcatheter that has been positioned immediately adjacent to or into the proximal cap of the occlusion. The catheters and arterial sheath will then be removed and the subject will be monitored overnight on the ward. The following day (Day1), the subject will be brought back to the catheterization laboratory and undergo an angioplasty using standard angioplasty techniques. Routine post-procedural management will then be followed. The subject will be discharged on Day2 in the absence of any cardiac complications (such as elevated cardiac enzymes or large pericardial effusion as judged by the Investigator and determined by echocardiography). Prior to the angioplasty procedure on Day1 and again on Day2 prior to discharge, the subject will undergo an echocardiogram to determine the presence and severity of a pericardial effusion. A moderate or large pericardial effusion or any sign of tamponade on Day1 will be a contraindication to performing the procedure, and the subject will be terminated from the study. A telephone follow-up will be performed 30 days post Day1 in all subjects who have signed an ICF and been enrolled in the study. At 3 months, subjects will undergo an outpatient coronary Computer Tomography (CT) angiogram to ensure there are no delayed effects on the treated vessel (e.g. aneurysm formation), the myocardium or the pericardium.
The primary objective is to evaluate the safety and tolerability of acute intracoronary doses of collagenase (MZ-004) in symptomatic subjects with coronary CTO.
The secondary objective is to obtain preliminary efficacy information of guidewire crossing with increasing doses of intracoronary collagenase in subjects with previously failed at least one previous attempt in coronary CTO.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Collagenase (MZ-004) | Experimental | Biological: collagenaseLocal intra-coronary administration of MZ-004 at or into the CTO |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subject is willing and able to provide an informed consent
- Subject is willing and able to comply with the study procedures and follow-up
- Subject is 35 years of age or older
- Women who are non-reproductive, or reproductive women who are willing and able to practice effective birth control methods. A urine pregnancy test should be done at the screening/Day0 on all reproductive women of child bearing ability
- Subjects with CTO (older than 6 weeks or unknown duration based on the investigator's assessment of appropriateness for the study) with a clinical indication for revascularization. In subjects with occlusions of unknown duration, there must be absence of any identifiable ischemic event in the 6 weeks prior to enrolment in the study
Key exclusion criteria (12 listed)
- Candidates for this study who meet any of the following criteria at the time of the screening visit are NOT eligible to be enrolled in this study:
- Culprit vessel is a saphenous vein graft occlusion
- True ostial LAD, LCX or RCA occlusions (since collagenase delivery will be unreliable)
- Presence of moderate or large pericardial effusion on echocardiogram within 2 weeks of the procedure
- Major side branch (1.5 mm diameter) within 3 mm proximal to the occlusion. (This is to prevent the infusate being diverted through a side branch and to prevent ischemia during the prolonged period of time during the infusion)
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 |
|---|---|---|
| collagenaseAlso: MZ-004Lyophilized powder / sterile dosage form for single local intravascular administration via the occluded coronary. | Biological | Collagenase (MZ-004) |
Primary outcome
Safety
Time frame: At 3 months
* Major Adverse Cardiac events, AE and SAE. * Cardiac enzymes, hematology and biochemistry; changes between Screening relative to Days 1 \& 30. * Vital Signs * A 2D-echocardiogram examination will be done on Day1 (18-24 hours after the collagenase administration prior to the CTO crossing procedure) and again on Day2 prior to discharge.
2 secondary outcomes
Efficacy
Time frame: Day 2
Pharmacokinetic
Time frame: PK blood draws will be assessed at 15, 30, 60, 120, 240, 480 min. and 18 hrs post removal of microcatheter
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2012.
- Derived from this study: PubMed 22179536Strauss BH, Osherov AB, Radhakrishnan S, Mancini GB, Manners A, Sparkes JD, Chisholm RJ. Collagenase Total Occlusion-1 (CTO-1) trial: a phase I, dose-escalation, safety study. Circulation. 2012 Jan 24;125(3):522-8. doi: 10.1161/CIRCULATIONAHA.111.063198. Epub 2011 Dec 16.
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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.
Bradley Strauss, MD, PhD, FRCP(C) principal investigator
Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing collagenase in people with Chronic Total Occlusions, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
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 8 inclusion and 12 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: finished, as of the sponsor's last update on 23 Mar 2012. 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 Canada. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety (time frame: At 3 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 NCT01271335, 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 23 Mar 2012.