Contact information
Type
Scientific
Primary contact
Dr S L M A Beeres
ORCID ID
Contact details
Leiden University Medical Centre
Department of Cardiology
P.O. Box 9600
Leiden
2300 RC
Netherlands
+31 (0)71 526 2020
s.l.m.a.beeres@lumc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR400
Study information
Scientific title
Acronym
Study hypothesis
The aim of this study is to determine the safety and efficacy of intramyocardial injection of autologous bone marrow cells in no-option patients with refractory angina pectoris and documented myocardial ischaemia.
Ethics approval
Received from the local medical ethics committee
Study design
Randomised, double-blind, placebo controlled, parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Angina pectoris, myocardial ischaemia
Intervention
After written informed consent has been obtained, quality of life and exercise capacity will be investigated. In addition myocardial function and perfusion will be documented. Bone marrow will be aspired from the iliac crest under local anesthesia. Patients will be randomised to receive bone marrow cells or placebo. In all patients NOGA™ mapping will be performed with subsequent intramyocardial injection of autologous bone marrow-derived mononuclear cells or placebo.
Quality of life and exercise capacity will be re-assessed at 3 and 6 months follow-up. In addition, changes in myocardial function and perfusion will be evaluated at 3 months follow-up.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measures
The change in myocardial perfusion (SPECT) at 3 months follow-up relative to baseline.
Secondary outcome measures
Efficacy:
1. Clinical end points:
1.1. Angina frequency
1.2. Canadian cardiovascular society score
1.3. Quality of life
1.4. Exercise capacity
2. Functional end points:
2.1. Change in left ventricular (LV) ejection fraction at 3 months follow-up
2.2. Regional myocardial function on a segmental base at 3 months follow-up
3. Safety:
3.1. Occurrence of arrhythmias
3.2. Pericardial effusion greater than 5 mm (echo)
3.3. Myocardial damage
3.4. Severe inflammation
Overall trial start date
01/05/2005
Overall trial end date
01/05/2007
Reason abandoned
Eligibility
Participant inclusion criteria
1. Severe refractory angina despite optimal medical therapy
2. Reversible ischaemia on gated-single photon emission computed tomography (SPECT)
3. Not a candidate for (repeat) revascularisation (coronary artery bypass graft [CABG] or percutaneous coronary intervention [PCI])
4. Male or female, greater than 18 years old
5. Patients must be stable (e.g. not be in a setting of life-threatening heart failure)
6. Written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
40
Participant exclusion criteria
1. Acute myocardial infarction, PCI or CABG within 6 months of enrolment in the study
2. History of malignancy (except low grade and fully resolved non-melanoma skin malignancy)
3. Unexplained haematological or biochemical abnormalities
4. Concurrent participation in a study using an experimental drug or an experimental procedure within 6 months before the injection procedure
5. Other severe concurrent illnesses (e.g. active infection, aortic stenosis, renal failure)
6. Bleeding diathesis or human immunodeficiency virus (HIV) infection
7. Inability to follow the protocol and comply with follow-up requirements
Recruitment start date
01/05/2005
Recruitment end date
01/05/2007
Locations
Countries of recruitment
Netherlands
Trial participating centre
Leiden University Medical Centre
Leiden
2300 RC
Netherlands
Sponsor information
Organisation
Leiden University Medical Centre (LUMC) (The Netherlands)
Sponsor details
Department of Cardiology
P.O. Box 9600
Leiden
2300 RC
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Leiden University Medical Centre (LUMC) (Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19454638
2. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21209073
2. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/23137509
Publication citations
-
Results
van Ramshorst J, Bax JJ, Beeres SL, Dibbets-Schneider P, Roes SD, Stokkel MP, de Roos A, Fibbe WE, Zwaginga JJ, Boersma E, Schalij MJ, Atsma DE, Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial., JAMA, 2009, 301, 19, 1997-2004, doi: 10.1001/jama.2009.685.
-
Results
van Ramshorst J, Antoni ML, Beeres SL, Roes SD, Delgado V, Rodrigo SF, de Roos A, Holman ER, Fibbe WE, Lamb HJ, Zwaginga JJ, Boersma E, van der Wall EE, Schalij MJ, Atsma DE, Bax JJ, Intramyocardial bone marrow-derived mononuclear cell injection for chronic myocardial ischemia: the effect on diastolic function., Circ Cardiovasc Imaging, 2011, 4, 2, 122-129, doi: 10.1161/CIRCIMAGING.110.957548.
-
Results
Rodrigo SF, van Ramshorst J, Beeres SL, Al Younis I, Dibbets-Schneider P, de Roos A, Fibbe WE, Zwaginga JJ, Schalij MJ, Bax JJ, Atsma DE, Intramyocardial injection of bone marrow mononuclear cells in chronic myocardial ischemia patients after previous placebo injection improves myocardial perfusion and anginal symptoms: an intra-patient comparison., Am. Heart J., 2012, 164, 5, 771-778, doi: 10.1016/j.ahj.2012.08.008.