Condition category
Circulatory System
Date applied
27/01/2006
Date assigned
27/01/2006
Last edited
09/01/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.lumc.nl/english/start_english.html

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

  1. 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.

  2. 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.

  3. 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.

Additional files

Editorial Notes