Using stem cells to treat patients with severe angina

A Phase II Randomised Sham-controlled Trial Assessing the Safety and Efficacy of Intracoronary Administration of Autologous Bone Marrow Cells in Patients With Refractory Angina

This study is testing whether using stem cells from patients' own bone marrow can help people with severe angina feel better and improve their quality of life.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 110 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Barts & The London NHS Trust (other)
• Locations: 1 site (London, England)
• Trial ID: NCT05711849 on ClinicalTrials.gov

What this trial studies

REGENERATE-COBRA is a Phase 2 clinical trial that investigates the safety and effectiveness of autologous stem cell treatment for patients suffering from refractory angina. Participants will be randomly assigned to either a treatment group, receiving stem cells derived from their own bone marrow, or a sham group, undergoing a placebo procedure. The study aims to assess changes in angina symptoms and quality of life over a 12-month follow-up period, with the primary endpoint being the change in Canadian Cardiovascular Society angina score at 6 months. All patients will be blinded to their treatment assignment to ensure unbiased results.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with symptomatic coronary artery disease and persistent refractory angina despite maximally tolerated medical therapy.

Not a fit: Patients who have viable options for revascularization or those with non-reversible ischemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients with refractory angina who have limited treatment options.

How similar studies have performed: While the use of stem cells in cardiac applications is being explored, this specific approach in refractory angina is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Subject is older than 18 years of age
2. Symptomatic coronary artery disease (CAD) with greater than or equal to 90 days of persistent refractory angina pectoris classified as CCS Grade III or IV despite maximally tolerated guideline directed medical therapy
3. Must have attempted treatment with the maximally tolerated dose of at least two of the four approved classes of anti-anginal agents: long-acting nitrates, calcium channel blockers (either a dihydropyridine or a non-dihydropyridine), beta blockers, and ranolazine. The regimen must be stable for greater than 2 months prior to enrolment, with no intent to change the medical regimen for at least 12 months after randomisation
4. Subject has either no treatment options for revascularization by coronary artery bypass grafting or by percutaneous coronary intervention, or is otherwise unsuitable or high risk for revascularization
5. Evidence of either exercise or pharmacologically induced reversible ischemia severity by stress echo, nuclear study, PET, perfusion MRI, CT perfusion, FFRCT, FFR, iFR, or other non-hyperaemic tests.
6. Functional limitation due to refractory angina as defined by a modified Bruce exercise tolerance test duration of greater than or equal to 2 minutes but less than or equal to 8 minutes
7. Left ventricular ejection fraction (LVEF) greater than or equal to 30% within the 12- months prior to procedure (must be reassessed after any intervening myocardial infarction); the most recent LVEF assessment is used as the qualifying test
8. Subject is willing and able to sign informed consent
9. Subject is willing to comply with the specified follow-up evaluations

Exclusion Criteria:

1. Recent (within 30 days prior to enrolment) troponin or CKMB positive acute coronary syndrome (NSTEMI or STEMI).
2. Recent successful revascularization by CABG or PCI within six months prior to enrolment
3. Recent unsuccessful PCI (e.g., no relief from symptoms, failed attempt to open a chronic total occlusion) within 30 days prior to enrolment
4. The predominant manifestation of angina is dyspnoea
5. Has extra-coronary contributory causes of angina - e.g., untreated hyperthyroidism, anaemia (hgb \<10 g/dL), uncontrolled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg despite medications), atrial fibrillation with rapid ventricular response (consistently \>100 bpm despite medications) or other tachyarrhythmia, severe aortic stenosis, hypertrophic cardiomyopathy with left ventricular outflow tract obstruction or asymmetric septal hypertrophy (concentric left ventricular hypertrophy is not an exclusion criterion), etc.
6. NYHA Class III or IV heart failure (HF), decompensated HF or hospitalisation due to HF during the 90 days prior to enrolment
7. Life threatening rhythm disorders or any rhythm disorders that would require future placement of an internal defibrillator and/or pacemaker
8. Severe chronic obstructive pulmonary disease (COPD) as indicated by a forced expiratory volume in one second (FEV1) that is less than 55% of the predicted value, or need for home daytime oxygen or oral steroids
9. Severe valvular heart disease (any valve)
10. Moderate or severe RV dysfunction by echocardiography
11. Chronic severe renal failure (estimated eGFR less than 30 mL/min/1.73m2 by the MDRD formula)
12. Any clinical condition that might interfere with the trial protocol or the subject's ability to be compliant with the trial protocol (e.g., active alcohol or drug abuse, dementia, etc.)
13. Currently enrolled in another investigational device or drug trial that has not reached its primary endpoint or that might clinically interfere with the current trial endpoints or procedures
14. Pregnant or planning pregnancy within the next 12 months (women of reproductive potential must have a negative pregnancy test within 7 days of the randomisation procedure)\*
15. Subject is part of a vulnerable population who, in the judgment of the investigator, is unable to give Informed Consent for reasons of incapacity, immaturity, adverse personal circumstances or lack of autonomy. This may include individuals with mental disability, persons in nursing homes, children, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces, and persons kept in detention.
16. Inability to tolerate dual antiplatelet therapy for 1 month if not on a chronic oral anticoagulant, or inability to tolerate a P2Y12 inhibitor for at least 1 month if on a chronic oral anticoagulant
17. Comorbidities limiting life expectancy to less than one year if recorded in patient's notes
18. Documented acute infection in patient's notes
19. Immunosuppressive medication
20. Inability to understand written and verbal English

Where this trial is running

London, England

• St Bartholomew's Hospital — London, England, United Kingdom (RECRUITING)

Study contacts

• Principal investigator: Anthony Mathur — Barts & The London NHS Trust
• Study coordinator: Stem Cell Research Team

Conditions: Refractory Angina Pectoris, Refractory Angina, Angina, Autologous stem cells, Stem cells