Trial of beta blocker therapy (atenolol) vs. angiotensin II receptor blocker therapy (losartan) in individuals with Marfan syndrome - Marfan Trial

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2006-003991-37-BE
• Date of registration: 06/12/2006
• Prospective Registration: Yes
• Primary sponsor: University Hospital Gent
• Public title: Trial of beta blocker therapy (atenolol) vs. angiotensin II receptor blocker therapy (losartan) in individuals with Marfan syndrome - Marfan Trial
• Scientific title: Trial of beta blocker therapy (atenolol) vs. angiotensin II receptor blocker therapy (losartan) in individuals with Marfan syndrome - Marfan Trial
• Date of first enrolment: 13/12/2006
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-003991-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Belgium

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible for this trial the subjects must meet all of the following inclusion criteria at the time of enrollment:
1) Diagnosis of MFS according to Ghent criteria
2) Age 6 months to 25 years.
3) Aortic root Z-score > 3.0.
4) Informed consent of parent(s) or legal guardian; informed consent or assent of subject as applicable.

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
To be eligible for this trial, the subjects must meet none of the following exclusion criteria at the time of enrollment:
1) Prior aortic surgery.
2) Aortic root dimension at the sinuses of Valsalva > 5 cm.
3) Planned aortic surgery within 6 months of enrollment.
4) Aortic dissection.
5) Shprintzen-Goldberg syndrome
6) Loeys-Dietz syndrome
7) Therapeutic (e.g. for arrhythmia, ventricular dysfunction or valve regurgitation) rather than prophylactic use of ACE inhibitor, BB, or calcium channel blocker.
8) History of angioedema while taking an ACE inhibitor or BB.
9) Intolerance to losartan or other ARB that resulted in termination of therapy.
10) Intolerance to atenolol or other BB that resulted in termination of therapy.
11) Renal dysfunction (Creatinine >upper limit of age-related normal values).
12) Asthma of sufficient severity to preclude the use of a BB: Chronic use of steroids and/or beta-adrenergic agents with exacerbations of asthma that are frequent (averaging three or more per year) or severe (requiring hospitalization).
13) Diabetes mellitus.
14) Pregnancy or planned pregnancy within 36 months of enrollment.
15) Inability to complete study procedures including history of poor acoustic windows (inability to obtain accurate measurement of aortic root).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Marfan syndrome
MedDRA version: 8.1 Level: LLT Classification code 10026829 Term: Marfan's syndrome

Intervention(s)

Product Name: losartan
Pharmaceutical Form: Tablet
INN or Proposed INN: Losartan potassium
CAS Number: 124750998
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Product Name: losartan
Pharmaceutical Form: Tablet
INN or Proposed INN: Losartan potassium
CAS Number: 124750998
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Name: losartan
Pharmaceutical Form: Tablet
INN or Proposed INN: Losartan potassium
CAS Number: 124750998
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Atenolol
Pharmaceutical Form: Tablet
INN or Proposed INN: Atenolol
CAS Number: 29122687
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Name: Atenolol
Pharmaceutical Form: Tablet
INN or Proposed INN: Atenolol
CAS Number: 29122687
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Atenolol
Pharmaceutical Form: Tablet
INN or Proposed INN: Atenolol
CAS Number: 29122687
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): Rate of change in aortic root (sinuses of Valsalva) BSA-adjusted Z-score

Main Objective: To compare the effect of beta blockers therapy to that of angiotension II receptor blocker therapy on the rates of aortic growth and progression of aortic regurgitation.

Secondary Objective: - To compare the effect of beta blockers therapy to that of angiotension II receptor blocker therapy on the incidence of the following cardiovascular events: aortic dissection, aortic root surgery, and death
- To compare the effect of beta blockers therapy to that of angiotension II receptor blocker therapy on the progression of mitral regurgitation
- To compare the effect of beta blockers therapy to that of angiotension II receptor blocker therapy on left vertricular size and function
- To compare the effect of beta blockers therapy to that of angiotension II receptor blocker therapy on echocardiographically-derived measures of central aortic stiffness
- To compare the effect of beta blockers therapy to that of angiotension II receptor blocker therapy on skeletal and somatic growth
- To compare the effect of beta blockers therapy to that of angiotension II receptor blocker therapy on the incidence of reported adverse drug reactions

Secondary ID(s)

AGO/2006/009