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.
REGENERATE-COBRA is a single centre, randomised (1:1) sham-controlled clinical trial taking place at St Bartholomew's Hospital in London, UK. * It is recruiting 110 symptomatic refractory angina patients. * All participants will be blinded to their treatment arm. They will wear a blindfold and noise cancelling headphones for the bone marrow aspiration and the infusion procedures. * Patients allocated to the treatment arm will undergo a bone marrow aspiration. After cell processing, the autologous bone marrow-derived mononuclear cells are infused into the coronary arteries using the stop-flow technique. * Patients allocated to the sham arm will undergo a sham bone marrow aspiration (a 3mm nick in the skin under local anaesthetic) and a sham cell infusion (a radial or femoral sheath will be inserted under local anaesthetic). * All patients will be followed up with a phone call at 1 month and 12 months, and a clinic visit at 6 months. * The primary endpoint is change in Canadian Cardiovascular Society (CCS) angina score at 6 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
110
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).
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).
St Bartholomew's Hospital
London, England, United Kingdom
RECRUITINGTo 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.
Time frame: Measured pre procedure (baseline) and at 6 months post procedure
To compare the safety of an intracoronary administration of autologous bone marrow derived cells versus sham as measured by adverse events
Count of number of adverse events occuring in all participants
Time frame: 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
The change in myocardial ischaemia as measured by perfusion imaging in all participants
Time frame: 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
The change in EQ-5D scores in all participants. Where the higher calculated score indicates a positive outcome.
Time frame: 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)
The change in SAQ scores in all participants. Where the higher calculated score indicates a positive outcome.
Time frame: 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
The change in total exercise time obtained by modified Bruce protocol in all participants
Time frame: 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 as measured by angina frequency
The change in number of episodes of angina occuring in a four week period prior to baseline, 6 months and 1 year visit in all participants
Time frame: Measured pre procedure (baseline) and at 6 months post procedure and 1 year post procedure
To compare the safety of an intracoronary administration of autologous bone marrow- derived cells versus sham as measured by major adverse cardiovascular events (MACE; defined as non-fatal stroke, non-fatal myocardial infarction and cardiovascular death)
The number of major adverse events to occur measured at 6 months and 1 year in all participants
Time frame: Measured 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 as measured by change in Canadian Cardiovascular Society angina score
The change in the Canadian Cardiovascular Society (CCS) angina scores in all participants. Scoring is via Class I-IV where class IV is worse outcome.
Time frame: Measured at 6 months post procedure and 1 year post procedure
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