Chronic Total Occlusions Clinical Trial
Official title:
Collagenase Total Occlusion-1 Trial
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).
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.
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02084888 -
Prognostic Impact of Chronic Total Occlusions
|
N/A |