|- candidate number||3089|
|- NTR Number||NTR1205|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||10-mrt-2008|
|- Secondary IDs||FI 0610 Foreest Institute Alkmaar|
|- Public Title||Randomised trial to evaluate the clinical value of intensive glucose monitoring and regulation in Myocardial Infarction|
|- Scientific Title||Randomised trial to evaluate the clinical value of intensive glucose monitoring and regulation in Myocardial Infarction|
|- ACRONYM||BIOMArCS-2; glucose regulation |
|- hypothesis||We postulate the following hypotheses: |
1. In patients presenting with myocardial infarction high serum glucose values at admission has a harmful influence on infarct size and left ventricular function (LVF)
2. Systematic, frequent and intensive glucose level control, with IV insulin in those with abnormal levels will improve LV hemodynamics in ACS patients. This by preserving myocardial tissue and LV function.
3. The beneficial effects of this strategy are modified by treatment delay (i.e. early treatment results in better outcomes), especially in STE-ACSpatients.
4. Effects of intensive insulin can be found on a cellular level as a more favorable biomarker wash out pattern.
|- Healt Condition(s) or Problem(s) studied||Acute coronary syndrome (ACS), Myocardial infarction , Hyperglycemia|
|- Inclusion criteria||Patients to be included must meet the following three criteria:|
1. Men or women >18 years of age who are admitted with the clinical diagnosis of a myocardial infarction. The diagnosis should be based on the combination of typical ischemic chest complaints and objective evidence of myocardial ischemia or myocardial necrosis as demonstrated by the electrocardiogram (ECG) or elevated cardiac markers, as follows:
- Typical ischemic chest pain, lasting 10 minutes or more, with the onset of symptoms within the preceding 24 hours, and
- ECG changes indicative of myocardial ischemia within 24 hours after the onset of chest pain (ECG showing new persistent or non-persistent ST-segment elevation >1.0 mm in two or more contiguous leads)
- Elevated biomarkers of myocardial necrosis within 24 hours after the onset of chest pain (i.e. CK-MB >1 times the upper limit of normal of the laboratory ( >16 U/L), or Troponin-I > 0.45 ng/ml).
2. Elevated (>7.8 mmol/L) whole blood glucose at admission in patients without a history of insulin dependent diabetes mellitus. (Patients only on oral anti-diabetic agents (NIDDM) can be included)
3. All patients have to provide written informed consent.
|- Exclusion criteria||Patients will be excluded from this study for any of the following reasons: |
1. Myocardial ischemia precipitated by a condition other than atherosclerotic coronary artery disease (e.g. arrhythmia, severe anemia, hypoxia, thyrotoxicosis, cocaine, severe valvular disease, hypotension).
2. Known severely-impaired left ventricular function (ejection fraction <30%) or end-stage congestive heart failure NYHA-class III or IV at presentation (in order to avoid lost-to-follow-up due to non-acute coronary syndrome events).
3. Severe chronic kidney disease with measured or calculated glomerular filtration rate (Cockgroft-Gault or MDRD4 (Modification of Diet in Renal Disease) formula) of <30 ml/min/1.73m2, or renal dialysis38.
4. Persistent atrial fibrillation.
5. Co-existent condition associated with a life-expectancy <1 year, or otherwise unlikely to appear at all scheduled follow-up visits.
6. Patient expected to be transferred to another hospital within 48 hours.
7. Insulin Dependent Diabetes Mellitus
|- mec approval received||yes|
|- multicenter trial||no|
|- control||Not applicable|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mei-2008|
|- planned closingdate||1-feb-2012|
|- Target number of participants||300|
|- Interventions||Treatment for this study only involves managing glucose levels and will not interfere with other treatment strategies, which will be applied according to international guidelines for myocardial infarction at the discretion of the attending physician.|
When admission plasma glucose is ¡Ý7.8 mmol/l patients will be asked to participate in our study. Plasma glucose levels are automatically assessed by converting whole blood glucose levels obtained by Point-of-Care (P-O-C)Glucometer into plasma levels.
Study therapy should be initiated within 2 hours of presentation.
When the patient agrees to participate he/she will be randomly assigned either to the intensive treatment group or to the regular treatment group.
|- Primary outcome||Extent of myocardial damage expressed by Troponin T level at 72 hours (48 - 96 hours) after admission. If more than one sample is drawn in this time frame, the sample closest to 72 hours will be used.|
|- Secondary outcome||1. Differences in biomarker wash out patterns between intensive and regularly treated patients;|
2. Left Ventricle Ejection Fraction (LVEF) and infarct size will be measured using a 99mTc-sestamibi SPECT 6 weeks after the event (+/- 1 week).This as we expect the remodelling of the heart has settled at this stage;
3. Extend of myocardial damage as expressed by area under CKMB curve.
The CKMB curve will be made of serial measurements of CKMB; at presentation and 6, 12, 24, 36, and 72 hours after enrolment;
4. ST segment resolution;
5. Serum NTpro BNP values;
6. Mortality and non fatal re-infarction (>72 hr after primary event) at 6 weeks;
7. HbA1C and fasting glucose values at 6 weeks;
8. The area under the Troponin T wash out curve (AUC) using the samples collected during admission.
|- Timepoints||6 week follow up|
|- Trial web site||http://www.biomarcs.org |
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||dr. V.A.W.M. Umans|
|- CONTACT for SCIENTIFIC QUERIES||dr. V.A.W.M. Umans|
|- Sponsor/Initiator ||Foreest Institute Alkmaar|
(Source(s) of Monetary or Material Support)
|Foreest Institute Alkmaar|
|- Publications||De Mulder et al Intensive management of hyperglycaemia in acute coronary syndromes. Study design and rationale of the BIOMArCS 2 glucose trial.
Diabet Med. 2011 Apr 11. doi: 10.1111/j.1464-5491.2011.03307.x (PMID 21480974)|
|- Brief summary||The statistical analysis plan can be seen through this link:|
|- Main changes (audit trail)||The statistical analysis plan has been added on 11-Aug-2012 - NM|
|- RECORD||27-feb-2008 - 13-aug-2012|