Assessing the Safety and Effectiveness of Intracoronary Stem Cells in Patients With Refractory Angina

NCT05711849 | Recruiting Phase 2 DMC

• 1 other identifier: 1005427
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

REGENERATE-COBRA will examine whether autologous stem cell treatment can improve angina symptoms and quality of life for patients with refractory angina. Patients will be randomised (randomly allocated with a 50:50 chance) to either the 'treatment' or the 'sham' group - they will not know which group they are in. In the 'treatment' group:

• Stem cells will be collected from bone marrow in the patient's hip under local anaesthetic (a bone marrow aspiration).
• Under local anaesthetic, the stem cells will be infused into the arteries that supply blood to the heart through a small tube inserted either in the wrist or the groin.
• The follow-up involves a phone call at 1 month and 12 months and clinic visit at 6 months. In the 'sham' group:
• A sham bone marrow aspiration is performed - a 3mm nick in the skin will be made under local anaesthetic.
• A sham cell infusion is performed - a small tube is inserted either in the wrist or groin under local anaesthetic.
• The follow-up involves a phone call at 1 month and 12 months and clinic visit at 6 months.

Conditions

Refractory Angina Pectoris; Refractory Angina

Keywords

Angina; Autologous stem cells; Stem cells

Outcome Measures

Primary Outcomes (1)

• To compare the effect of an intracoronary administration of autologous bone marrow-derived cells to a placebo sham treatment on Canadian Cardiovascular Society (CCS) angina scores in patients with refractory angina.

  The change in Canadian Cardiovascular Society (CCS) angina scores in all participants. Scoring is via Class I-IV where class IV is worse outcome.

  Measured pre procedure (baseline) and at 6 months post procedure

Secondary Outcomes (8)

• To compare the safety of an intracoronary administration of autologous bone marrow derived cells versus sham as measured by adverse events

  Measured at 1 week post procedure, 6 months post procedure and 1 year post procedure

• To compare the efficacy of an intracoronary administration of autologous bone marrow-derived cells versus sham on myocardial ischaemic burden as measured by clinically indicated perfusion imaging

  Measured pre procedure (baseline) and at 6 months post procedure

• To compare the efficacy of an intracoronary administration of autologous bone marrow-derived cells versus sham on quality of life as measured by EQ-5D

  Measured pre procedure (baseline) and at 6 months post procedure and 1 year post procedure

• To compare the efficacy of an intracoronary administration of autologous bone marrow-derived cells versus sham on quality of life as measured by Seattle Angina Questionnaire (SAQ)

  Measured pre procedure (baseline) and at 6 months post procedure and 1 year post procedure

• To compare the efficacy of an intracoronary administration of autologous bone marrow-derived cells versus sham on total exercise time as measured by a modified Bruce protocol exercise treadmill test

  Measured pre procedure (baseline) and at 6 months post procedure

Study Arms (2)

Treatment arm

EXPERIMENTAL

Bone marrow aspiration and a single intracoronary infusion of autologous bone marrow-derived mononuclear cells.

Biological: Bone marrow aspiration and a single intracoronary infusion of autologous bone marrow-derived mononuclear cells.

Sham arm

SHAM COMPARATOR

Sham bone marrow aspiration and sham cell infusion (insertion of vascular access sheath).

Procedure: Sham bone marrow aspiration and sham cell infusion (insertion of vascular access sheath).

Interventions

Bone marrow aspiration and a single intracoronary infusion of autologous bone marrow-derived mononuclear cells. BIOLOGICAL

Bone marrow will be harvested from the posterior superior iliac crest under local anaesthetic, and mononuclear cells will be separated using a Ficoll technique in a certified laboratory. Later that same day, the participant will undergo an intracoronary cell infusion of the mononuclear cells. Participants will be blinded to their treatment arm (they will wear a blindfold and noise cancelling headphones for the bone marrow aspiration and cell infusion).

Treatment arm

Sham bone marrow aspiration and sham cell infusion (insertion of vascular access sheath). PROCEDURE

These participants will have a sham bone marrow aspiration (a 3mm incision in the skin under local anaesthetic) and a sham intracoronary infusion procedure (the insertion of radial or femoral sheath under local anaesthetic). Participants will be blinded to their treatment arm (they will wear a blindfold and noise cancelling headphones for the sham bone marrow aspiration and sham cell infusion).

Sham arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is older than 18 years of age
• 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
• 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
• 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
• 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.
• 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
• 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
• Subject is willing and able to sign informed consent
• Subject is willing to comply with the specified follow-up evaluations

You may not qualify if:

• Recent (within 30 days prior to enrolment) troponin or CKMB positive acute coronary syndrome (NSTEMI or STEMI).
• Recent successful revascularization by CABG or PCI within six months prior to enrolment
• Recent unsuccessful PCI (e.g., no relief from symptoms, failed attempt to open a chronic total occlusion) within 30 days prior to enrolment
• The predominant manifestation of angina is dyspnoea
• NYHA Class III or IV heart failure (HF), decompensated HF or hospitalisation due to HF during the 90 days prior to enrolment
• Life threatening rhythm disorders or any rhythm disorders that would require future placement of an internal defibrillator and/or pacemaker
• 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
• Severe valvular heart disease (any valve)
• Moderate or severe RV dysfunction by echocardiography
• Chronic severe renal failure (estimated eGFR less than 30 mL/min/1.73m2 by the MDRD formula)
• 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.)
• 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
• 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)\*
• 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.
• 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

Sponsors & Collaborators

• Barts & The London NHS Trust: lead

Study Sites (1)

St Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Angina Pectoris

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Anthony Mathur

  Barts & The London NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stem Cell Research Team

CONTACT

0203 765 8704; bhnt.stemcells@nhs.net

Alice Reid

CONTACT

a.e.reid@qmul.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II randomised sham-controlled trial

Study Record Dates

• First Submitted: January 25, 2023
• First Posted: February 3, 2023
• Study Start: March 1, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)