|- candidate number||3879|
|- NTR Number||NTR1423|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||26-aug-2008|
|- Secondary IDs||NL19860.018.07 EudraCT:2007-005413-19|
|- Public Title||Losartan and Marfan syndrome|
|- Scientific Title||Losartan therapy in patents with Marfan syndrome|
|- ACRONYM||COMPARE study|
|- hypothesis||Losartan reduces the aortic dilatation in patients with Marfan syndrome|
|- Healt Condition(s) or Problem(s) studied||Aneurysm, Marfan syndrome, Losartan |
|- Inclusion criteria||1. Marfan syndrome diagnosed according to Ghent criteria |
|- Exclusion criteria||1. More than one vascular prosthesis for the primary end-point evaluation. |
2. Aortic root dimension > 5 cm.
3. Not-treated hypertension
4. Blood pressure higher than 160/90 mmHg
5. Blood pressure lower than 90/60
6. Taking ACE inhibitors and/or Angiotensine II receptor antagonists for other indications than prevention of aortic growth.
7. Planned aortic surgery within the 6 months of study entry.
8. Incapable of giving informed consent.
9. Hypersensitivity to losartan or any of its additional substances.
10. History of angioedema while taking an ACE inhibitor.
11. Hypersensitivity to intravenous contrast agent.
12. Shprintzen-Goldberg syndrome. (clinical features listed in App. II will be evaluated)
13. Loeys-Dietz syndrome. (clinical features listed in App. II will be evaluated)
14. Known bilateral renal artery stenosis.
15. Myocardial infarction, stroke or open-heart surgery in the previous four weeks.
16. Renal dysfunction ( creatinine level > 130 ug/ml)
17. Pregnancy (a pregnancy test is offered to every female patient within the fertile age assigned to losartan), nursing or planned pregnancy within 36 months of enrollment.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||2-feb-2008|
|- planned closingdate||2-feb-2012|
|- Target number of participants||330|
|- Interventions||- MRI scan or if contraindicated, CT scan|
- Skin biopsy
- SF-36 quality of life questionnaire
|- Primary outcome||Largest change in absolute aortic diameter evaluated at all aortic levels in one patient: |
losartan group versus not-treated control group measured with MRA or Multi-slice CT.
|- Secondary outcome||• Change in mortality, incidence of newly diagnosed dissection in any main vessel and incidence of elective aortic surgery combined with the primary endpoint.|
• Change of aortic volume measured by MRA.
• Change of aortic wall stiffness measured by MRA.
• Change of left ventricular size and ejection fraction measured with MRI.
• Prediction model for aortic growth.
• Prediction model for treatment response to losartan therapy based on multiple biochemical, immunohystological and expression biomarkers.
• Change in the quality of life scores.
|- Timepoints||We expect the inclusion to last for 1.5 years. With the follow-up of 3 years, it is expected that this study will last for 4,5 years.|
|- Trial web site||http://www.comparestudy.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||MD research fellow T. Radonic|
|- CONTACT for SCIENTIFIC QUERIES||MD PhD M. Groenink|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Amsterdam|
(Source(s) of Monetary or Material Support)
|Academic Medical Center (AMC), Amsterdam|
|- Brief summary||Background: |
Aortic disease, leading to progressive aneurysmal dilatation and dissection is the main cause of morbidity and mortality of patients with Marfan syndrome (MFS). Current therapies, i.e. beta-blockers and elective surgery, do postpone but cannot prevent aortic complications in these patients. New insights in the etiology of the MFS proved the Transforming Growth Factor beta (TGF-beta) to play a causal role in the aortic dilatation. Angiotensin II receptor blocker losartan was found to be potentially useful in MFS because it leads to antagonism of TGF-©¬ in animal models.
We initiated a nationwide clinical trial to investigate effects of losartan in adult patients with MFS. The primary objective is to investigate the effect of losartan on the rate of aortic dilation over 3 years. Other objectives are to investigate the effect of losartan on aortic wall stiffness, volume, ventricular function and gene expression.
This is a prospective randomized open-label clinical trial with blinded end-points evaluation. 330 adult patients will be randomized to receive 100 mg losartan daily or not. A current treatment with ¥â blockers will not be discontinued. Aortic diameters, volume and stiffness and ventricular function will be investigated by means of MRI of the heart and entire aorta.
We expect that losartan will significantly reduce the occurrence and progression of aortic dilatation in Marfan patients making a substantial contribution to the management of adults with MFS.
|- Main changes (audit trail)|
|- RECORD||26-aug-2008 - 8-sep-2008|