Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01781390 |
| Other study ID # |
ANG.AMI-IC001 |
| Secondary ID |
2010-020497-41 |
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 11, 2013 |
| Est. completion date |
April 6, 2021 |
Study information
| Verified date |
June 2022 |
| Source |
Mesoblast, Ltd. |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This was a double-blind, randomized, placebo-controlled study that was designed to enroll a
total of 225 participants with de novo anterior wall acute ST-segment elevation myocardial
infarction (STEMI) due to a lesion of the left anterior descending coronary artery undergoing
percutaneous coronary intervention (PCI). Eligible participants were to be enrolled and
undergo revascularization of the culprit left anterior descending (LAD) coronary artery. The
interventional procedure included as dose ranging assessment of intracoronary (IC) delivery
of MPC or placebo infused into the stented coronary artery. This study compared two doses of
MPCs and a placebo control group. Study participants were randomly assigned in 1:1:1 fashion
to receive either 12.5 Million or 25 Million MPCs or placebo (saline). Initially, each group
was designed to have approximately 75 patients per treatment group. The Primary Objective of
the study was to determine the safety and feasibility of IC infusion of investigational MPCs
in this acute STEMI population.
The Primary Objective of the study was to determine the safety and feasibility of IC infusion
of investigational MPCs in this acute STEMI population. Feasibility of the infusion of the
investigational agent was assessed by measurement of thrombolysis in myocardial infarction
(TIMI) flow and perfusion (1) immediately prior to, (2) during (after approximately 50% of
total investigational agent volume infused) and (3) following the investigational agent
infusion after successful PCI and stenting. There was no evidence of clinically important
coronary microvascular obstruction related to infusion of the investigational agent.
Description:
This was a prospective, double-blind, randomized, placebo-controlled study that was designed
to enroll approximately 225 participants with de novo anterior STEMI due to a lesion
involving the proximal-mid LAD coronary artery who undergo primary PCI at approximately 45
clinical study sites. However, due to difficulty in consenting participants and
operationalizing the protocol under the emergency environment of an acute STEMI, it became
clear that a major protocol amendment would be required. Accordingly, the protocol was
adjusted to randomize 105 participants (35 per treatment group) at 25 clinical study sites.
This 53% reduction in participants from the original protocol allowed preliminary evaluations
of safety and feasibility.
Potential participants who were in the midst of experiencing an acute anterior wall STEMI,
where increased time to coronary revascularization is known to correlate with the extent of
subsequent myocardial necrosis, were approached by a study site investigator prior to PCI to
determine the participant's interest to participate in a stem cell investigational trial.
This required the patient to sign an informed consent permitting both the PCI procedure and
participation in the trial. Participants who agreed to participate in the AMICI study and had
a successful and uneventful PCI and stenting of the culprit LAD lesion performed were then
randomized to one of the three treatment groups. The randomization and treatment assignment
were obtained using an interactive voice-response system (IVRS/interactive web response
system [IWRS]). The following stratification for duration of cardiac ischemia was performed
to ensure balanced randomization across the treatment groups:
- ≤2 hours
- >2 hours to ≤6 hours
- >6 to ≤12 hours
Eligible participants received intracoronary delivery of the assigned treatment infused via a
microcatheter into the stented culprit artery.
After approximately 50% of the intracoronary infusion of investigational treatment was
completed, an angiographic determination of coronary flow was performed. The following
guidelines were used to determine if the remaining investigational agent should be infused:
The study infusion should have been continued if TIMI 2 or TIMI 3 flow was present in the
absence of ALL of the following;
- Sustained hypotension not responsive to fluid administration;
- Clinical signs/symptoms indicating an acute cerebrovascular event;
- Re-elevation of ST-segments if previously resolved with PCI;
- Onset of the participant's symptoms of myocardial ischemia unresponsive to appropriate
interventions;
- Two episodes of sustained ventricular tachycardia (VT)/ventricular fibrillation (VF)
requiring cardioversion (infusion can continue if a single episode of sustained VT/VF
requiring cardioversion occurred).
Feasibility of the infusion of the investigational agent was assessed by measurement of TIMI
flow and perfusion (1) immediately prior to, (2) during (after approximately 50% of total
investigational agent volume infused) and (3) following the investigational agent infusion
after successful PCI and stenting. There was no evidence of clinically important coronary
microvascular obstruction related to infusion of the investigational agent.
If, for any reason, the site investigator withdrew a randomized participant prior to infusion
of the investigational agent, the reason for early termination and data from the screening
visit were entered into the eCRF by the study site. The participant did not remain in the
study. If for any reason, a participant's study infusion was halted due to safety
considerations, the participant remained in the study. A participant who prematurely withdrew
from the study remained in the study for long-term safety follow-up.
Evaluation for safety was performed for up to 24 months post infusion for all non-Swedish
sites. Participants enrolled in Sweden who consented for additional follow-up underwent
safety assessments at 36, 48, and 60 months post-infusion of investigational agent. All
participants were to have cardiac imaging using cardiac magnetic resonance imaging [cMRI] and
2D-echocardiography, Holter monitoring, clinical evaluations, and laboratory testing as
outlined in the study protocol.
An independent Data Monitoring Safety Board (DSMB) reviewed all relevant acute
peri-procedural data, serious adverse events (SAE), other adverse events (AE), and efficacy
data (if requested) periodically until participant enrolment was closed.
