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CardiAMP CMI Randomized Controlled Pivotal Trial in Patients With Chronic Myocardial Ischemia and Refractory Angina (CardiAMP CMI)

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ClinicalTrials.gov Identifier: NCT03455725
Recruitment Status : Not yet recruiting
First Posted : March 7, 2018
Last Update Posted : March 9, 2018
Sponsor:
Information provided by (Responsible Party):
BioCardia, Inc.

Brief Summary:

Prospective, multi-center, 2:1 randomized (Treatment : Sham Control), sham-controlled, double-blinded trial to compare treatment using the CardiAMP cell therapy system to sham treatment

Treatment Group:

Subjects treated with aBMC using the CardiAMP cell therapy system

Sham Control Group:

Subjects treated with a Sham Treatment (no introduction of the Helix transendocardial delivery catheter, no administration of aBMC)


Condition or disease Intervention/treatment Phase
Refractory Angina Chronic Myocardial Ischemia Device: CardiAMP Cell Therapy System Other: Sham Treatment Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 343 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, multi-center, 2:1 randomized (Treatment vs Sham Control), blinded trial comparing 2 paralel groups of patients with CMI treated with CardiAMP cell therapy system vs sham treatment.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Quadruple-blinded, placebo-controlled study. Patients, investigators, the CRO, core labs and the sponsor will be blinded for individual treatment adjudication.
Primary Purpose: Treatment
Official Title: Randomized Controlled Pivotal Trial of Autologous Bone Marrow Cells Using the CardiAMP Cell Therapy System in Patients With Refractory Angina Pectoris and Chronic Myocardial Ischemia (CardiAMP CMI Trial)
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: CardiAMP cell therapy system

Roll-in phase:

Up to 10 subjects with refractory chronic myocardial ischemia CCS class III-IV will be treated in an unblinded, uncontrolled roll-in phase.

In the subsequent randomized phase:

Up to 333 subjects with refractory chronic myocardial ischemia CCS class III-IV will be randomized. Up to 222 Subjects will be randomized to treatment with the CardiAMP cell therapy system.

Device: CardiAMP Cell Therapy System
The CardiAMP Cell Therapy system consists of the CardiAMP Potency Assay, the Helix/Morph intramyocardial delivery catheter system, and the CardiAMP Cell Separator. The system allows the investigator to identify patients with a high chance to respond to im autologous stem cell therapy (using the CardiAMP Cell Potency Assay), to isolate the stem cells from a bone marrow harvest at the point of care (using the CardiAMP CS system), and to percutaneously inject the autologous cells into the myocardium using the Helix/Morph delivery catheters.

Sham Comparator: Sham procedure control

Randomized phase:

Up to 333 subjects with refractory chronic myocardial ischemia CCS class III-IV will be randomized. Up to 111 subjects will be treated with a Sham Treatment (no introduction of trans endocardial delivery catheter and no administration of autologous cells)

Other: Sham Treatment
Patients will receive sham bone marrow procedure and a ventriculogram. A scripted sham percutaneous procedure will be performed




Primary Outcome Measures :
  1. Change from Baseline in Total Exercise Time on the treadmill using the Modified Bruce Protocol [ Time Frame: Baseline and 12 months visit ]
    A superiority analysis with regards to change from Baseline in Total Exercise Time at the 12 months follow-up visit (using a Modified Bruce Protocol).


Secondary Outcome Measures :
  1. Safety: overall survival at 12 months follow-up [ Time Frame: at 12 months follow-up ]
    A non-inferiority analysis of overall survival at 12-months will be made comparing the Treatment group to the Sham Control group using a non-inferiority margin of 10%.

  2. Safety: Total Major adverse cardiac events (MACE) at 12 months follow-up [ Time Frame: from randomisation to 12 months follow-up ]
    A non-inferiority analysis with regard to Total Major Adverse Cardiac Events (MACE: defined as death, cardiac hospitalization, non-fatal myocardial infarction and stroke) at 12 month follow-up, as adjudicated by an independent clinical endpoint classification (CEC) committee with 10% margin.

  3. Efficacy: Change from baseline in Total Exercise Time at 6 months follow-up [ Time Frame: Baseline and at 6 months follow-up ]
    Superiority analysis with regards to change from baseline in Total Exercise Time on Exercise Tolerance Test (ETT) at 6 Month Follow-up Visit. Baseline (BL) is the average of (at least) two total exercise times measured during the screening period.

  4. Efficacy: Change of angina frequency (per week) at 12 months follow-up [ Time Frame: Baseline and at 12 months follow-up ]

    Superiority analysis with regards to change in angina frequency (episodes per week) at 12 month follow-up Visit versus baseline angina frequency (per week).

    Participants self-reported angina episodes utilizing an electronic diary for 4 weeks at baseline (screening period) and in the 4 weeks before the 12-month follow-up visits.


  5. Efficacy: Change of Angina Frequency (per week) at 6 months follow-up [ Time Frame: Baseline and at 6 months follow-up ]

    Superiority analysis with regards to change in angina frequency at 6 month follow-up visit versus baseline (expressed as angina frequency per week).

    Participants self-reported angina episodes utilizing an electronic diary for 4 weeks at baseline and in the 4 weeks before the 6-month follow-up visits.


  6. Safety: Total Major adverse cardiac events (MACE) at 24 months follow-up [ Time Frame: From randomisation to 24 month follow-up ]
    Superiority analysis with regards to incidence of MACE from Randomization until the end of the 24 month follow-up period

  7. Efficacy: Percentage of patients with at least 1 Serious Adverse Event (SAE) [ Time Frame: From randomization to 24 Months follow-up ]
    Superiority analysis with regards to percentage of participants with at least one SAE. From randomization until the end of the 24 month follow-up period.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participants who are 21 to 80 years of age at the time of signing the informed consent.
  2. Participants with Canadian Cardiovascular Society (CCS) class III or IV chronic refractory angina.
  3. Participants without control of their angina symptoms despite maximal tolerated doses of anti-angina drugs. Participants must be on optimal therapy for their angina and must have been on a stable anti-anginal medication regimen for at least 4 weeks before signing the informed consent form. Anti-angina drugs may include beta-blockers, calcium channel blockers, nitrates, and ranolazine;
  4. Participants must have evidence of inducible myocardial ischemia on baseline stress testing (within last year; including nuclear or CMR/MRI perfusion imaging, or significant STT depression analysis during exercise).
  5. Participants must have obstructive coronary disease, unsuitable for conventional revascularization due to unsuitable anatomy or comorbidity, as determined at the site and confirmed by an independent adjudication committee.

    Angiograms for each patient will be reviewed by an independent committee composed of interventional cardiologists and cardiac surgeons and will independently assess eligibility for revascularization.

  6. Participants must experience angina episodes at a minimum of 7 angina episodes per week (during a 4-week screening period)
  7. Participants must be able to complete 3 exercise tolerance tests on the treadmill using the modified Bruce protocol.

    Performance during the exercise test (TET) must be:

    • limited by angina or angina equivalent on each test
    • the total exercise test is on average between 3 and 10 min
    • the TET are reproducible within 20% between qualifying tests.
  8. If female of childbearing potential, subjects must not be pregnant and agree to employ adequate birth control measures for the duration of the study.
  9. Participants must have a left ventricular ejection fraction of more than 25% as measured by echocardiography.
  10. CMI Cell Potency Assay Score of 4, as determined by the Cell Analysis Core Lab analysis of the bone marrow aspirate.
  11. Participants must provide written informed consent

Exclusion Criteria

  1. Participants with a prior cardiovascular hospitalization for a PTCA, stroke or transient ischemic attacks within 60 days prior to potential study enrollment.
  2. Participants with a successful or partially successful coronary artery bypass graft (CABG) within 6 months or PCTA within 60 days of potential study enrollment.
  3. Participants with a placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT) for heart failure within 180 days of potential study enrollment.
  4. Participants with a prosthetic aortic valve or a mechanical mitral valve replacement.
  5. Participants with a documented aortic stenosis (with an orifice area of 1.5 cm(2) or less), severe aorta regurgitation, severe mitral regurgitation or stenosis as detected by the echocardiographic core laboratory
  6. Participants with a severe co-morbidity associated with a reduction in life expectancy to less than 3 years.
  7. Participants with cancer are excluded, with the following exceptions:

    • Subjects with in-situ non-melanoma skin cancer are not excluded.
    • Subject with in-situ cervical cancer are not excluded.
    • Participants that have been cancer free for more than 5 years (as determined by their oncologist) are not excluded.
  8. Participants with a prior history of stem cell transplant for cancer
  9. Participants with a history of leukemia, or other bone marrow disease, no matter how long they have been cancer-free.
  10. Participants with sickle cell disease or sickle cell trait.
  11. Participants with HbA1c > 9%.
  12. Participants with platelet counts >10% above the upper limit of normal (ULN) or platelet counts < 70,000.
  13. Participants with a hematocrit < 30% prior to potential study enrollment.
  14. Participants with a serum creatinine > 2.5 mg/dL prior to potential study enrollment.
  15. Participants with positive test for HIV, hepatitis B, or hepatitis C, or is on chronic immunosuppressive medications
  16. Participant was previously enrolled in an active treatment group of cell therapy trials for cardiovascular disease, including any phase of CD34+ stem cell trials.
  17. Participants with atrial fibrillation, atrial flutter, or other uncontrolled arrhythmias that would prohibit intra-myocardial injection.
  18. Participants with bleeding diathesis with an INR > 1.5 when not receiving anti-thrombotic therapy.
  19. Participants with any previous transplant requiring immunosuppression.
  20. Participants with a disease state requiring chronic immunosuppression.
  21. Participants with left ventricular thrombus, as detected by the echocardiographic core laboratory
  22. Participants with an acute coronary syndrome within 3 months
  23. Participants with evidence of a life-threatening arrhythmia (non-sustained ventricular tachycardia > 20 consecutive beats) or sustained or short run (>20 consecutive beats) ventricular tachycardia during the screening Holter Monitoring
  24. Participants with a complete heart block or QTc interval >550 ms on screening 12-lead ECG
  25. Participants with AICD firing in the past 60 days prior to the procedure
  26. Participants with peripheral artery disease, involving the aorta or iliofemoral system that impacts the feasibility or safety of the study intervention. This includes stenotic or aneurysmal or embolic disease, and symptom limiting claudication.
  27. Participants with participation in another clinical study within 30 days prior to study enrollment.
  28. Participants who are scheduled to participate in another clinical study involving an IP or device during the course of this study -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03455725


Contacts
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Contact: Peter Altman, PhD (650) 226 0135 info@biocardia.com
Contact: Eric Duckers, MD PhD FESC (650) 226 0135 info@biocardia.com

Sponsors and Collaborators
BioCardia, Inc.

Additional Information:
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Responsible Party: BioCardia, Inc.
ClinicalTrials.gov Identifier: NCT03455725     History of Changes
Other Study ID Numbers: 04747 (CLIN)
First Posted: March 7, 2018    Key Record Dates
Last Update Posted: March 9, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by BioCardia, Inc.:
Cardiovascular Stem Cell Therapy
Bone Marrow Mononuclear Stem Cells
Intramyocardial Injection

Additional relevant MeSH terms:
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Ischemia
Angina Pectoris
Myocardial Ischemia
Coronary Artery Disease
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases