E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In coronary artery disease atherosclerosis leads to a decrease in lumen diameter of the large epicardial arteries, causing a deficit in blood flow known as ischemia. This ischemia can cause chest pain, referred to as angina pectoris. Refractory angina pectoris is a disabling condition with an adverse prognosis with a high mortality rate. This severe disorder has a significant morbidity and impact on quality of life. Many patients have very limiting complaints, despite optimal medical therapy. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
We intend to assess the efficacy of repeat injection of bone marrow cells in patient with residual or recurrent refractory angina pectoris. Specifically, we want to answer the question whether injection of autologous mononuclear bone marrow cells into the myocardium of no-option patients with refractory angina and documented ischemia leads to an improvement in quality of life, myocardial perfusion, excercise capacity and myocardial function. |
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E.2.2 | Secondary objectives of the trial |
Repeat injection of autologous mononuclear bone marrow cells into the myocardium of no-option patients with residual or recurrent refractory angina pectoris and documented ischemia is safe with respect to arrhythmia's and periprocedural myocardial damage. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Having received intramyocardial bone marrow cell injection in study P02.051 (Injection of Autologous Bone Marrow Cells into Damaged Myocardium of No-option Patients with Refractory Angina Pectoris and Ischemia, a two-phased study of safety, feasibility and efficacy) or P05.025 (Efficacy assessment of intramyocardial injection of autologous bone marrow cells in no-option patients with refractory angina pectoris and documented ischemia, a randomized, double blind, placebo controlled study) - Disabling refractory angina pectoris despite optimal medical therapy - Residual reversible ischemia on GATED-SPECT imaging - No candidate for (repeat) revascularization. - Male or female, > 18 years old - Patients must be stable and not be in a setting of life-threatening heart failure (LVEF>35%) - Able to perform an exercise tolerance test prior to therapy - Able and willing to undergo all the tests used in this protocol including the traveling involved. - Written informed consent |
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E.4 | Principal exclusion criteria |
- Evidence of cancer (except low grade and fully resolved non-melanoma skin malignancy) as bone marrow cell infusion might promote tumor growth through induction of angiogenesis in the tumor. - Concurrent participation in a study using an experimental drug or an experimental procedure within 2 months before the injection procedure. - Other severe concurrent illnesses (e.g. active infection, aortic stenosis, renal failure) - Bleeding diathesis or HIV infection - Any other condition that, in the opinion of the investigator, could pose a significant threat to the subject if the investigational therapy was to be initiated. - Inability to undergo cardiac catheterization or nuclear testing - Inability to follow the protocol and comply with follow-up requirements - Candidates for surgical of percutaneous intervention - Mechanical aortic valve prosthesis |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: - Gated-SPECT: stress and rest perfusion score - FDG-SPECT: assessing viability and hibernation - MRI: left ventricular global ejection fraction - Echocardiography:left ventricular wall motion - Exercise tolerance testing with VO2 max determination - Quality of Life will be assessed using the Seattle Angina Questionnaire, translated into Dutch.
Safety: - holter recording: to assess the occurrence of arrhytmia's - blood sampels: to assess possible inflammation and myocardial damage |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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If the safety monitoring committee decides that serious events related to the therapy have occurred, which are a reason to cease the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |