TY - JOUR
T1 - Losartan therapy in adults with Marfan syndrome
T2 - Study protocol of the multi-center randomized controlled COMPARE trial
AU - Radonic, Teodora
AU - de Witte, Piet
AU - Baars, Marieke J.H.
AU - Zwinderman, Aeilko H.
AU - Mulder, Barbara J.M.
AU - Groenink, Maarten
AU - AUTHOR GROUP
AU - Bouma, Berto J.
AU - Timmermans, Janneke
AU - Hamel, Ben C. J.
AU - van den Berg, Maarten P.
AU - van Tintelen, Peter J.
AU - Scholte, Arthur J. H.
AU - Hilhorst-Hofstee, Yvonne
N1 - Funding Information: This study is supported by the Interuniversity Cardiology Institute of the Netherlands (ICIN) and Dutch Marfan Association. The study is funded by the Dutch Heart Association, grant 2008B115. COMPARE study group: Teodora Radonic, Aeilko H. Zwinderman, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center Amsterdam, the Netherlands. Piet de Witte, Berto J. Bouma, Barbara J. M. Mulder, Maarten Groenink, Department of Cardiology, Academic Medical Center Amsterdam, the Netherlands. Marieke J. H Baars, Department of Clinical Genetics, Academic Medical Center Amsterdam, the Netherlands. Janneke Timmermans, Department of Cardiology, University Medical Center St. Radboud, Nijmegen, the Netherlands. Ben CJ Hamel, Department of Clinical Genetics, University Medical Center St. Radboud, Nijmegen, the Netherlands. Maarten P. van den Berg, Department of Cardiology, University Medical Center Groningen, the Netherlands. Peter J. van Tintelen, Department of Clinical Genetics, University Medical Center Groningen, the Netherlands. Arthur J. H. Scholte, Department of Cardiology, Leiden University Medical Center, the Netherlands. Yvonne Hilhorst-Hofstee, Department of Clinical Genetics, Leiden University Medical Center, the Netherlands
PY - 2010/1/12
Y1 - 2010/1/12
N2 - Background: Marfan syndrome (MFS) is one of the most common systemic disorders of connective tissue with the incidence of approximately 2-3 per 10 000 individuals. Aortic disease, leading to progressive aneurysmal dilatation and dissection is the main cause of morbidity and mortality of Marfan patients. Current treatment (e.g. beta blockers and elective surgery) does postpone but cannot prevent aortic complications in these patients. Recent studies have found Transforming Growth Factor β (TGF β) to be involved in the aortic aneurysm formation. Losartan, an Angiotensin II type 1 receptor blocker inhibits TGFβ in a mouse model of Marfan syndrome leading to inhibition of aortic growth. The main objective of this trial is to assess whether losartan treatment leads to a clinically relevant decrease of aortic dilatation in adult patients with Marfan syndrome.Methods/Design: COMPARE study (COzaar in Marfan Patients Reduces aortic Enlargement) is an open-label, randomized, controlled trial with blinded end-points. Treatment with losartan will be compared with no additional treatment after 3 years of follow-up. We will enroll 330 patients with MFS who will be randomly assigned to receive losartan or not. Patients taking beta-blockers will continue taking their standard treatment. The primary end-point is the largest change in aortic diameter at any aortic level measured by means of MRI. Secondary end-points are change in mortality, incidence of dissection, elective aortic surgery, aortic volume, aortic stiffness and ventricular function. We will also investigate gene and protein expression change in the skin under losartan therapy and create prediction models for losartan-treatment response and aortic dilatation.Discussion: The COMPARE study will provide important evidence of effects of losartan treatment in adult Marfan patient population. We expect losartan to significantly reduce the occurrence and progression of aortic dilatation. This trial investigates a wide spectrum of clinical, genetic and biochemical effects of losartan aiming to provide further insight in the pathogenesis and treatment of Marfan syndrome.Trial registration: Netherlands Trial Register NTR1423.
AB - Background: Marfan syndrome (MFS) is one of the most common systemic disorders of connective tissue with the incidence of approximately 2-3 per 10 000 individuals. Aortic disease, leading to progressive aneurysmal dilatation and dissection is the main cause of morbidity and mortality of Marfan patients. Current treatment (e.g. beta blockers and elective surgery) does postpone but cannot prevent aortic complications in these patients. Recent studies have found Transforming Growth Factor β (TGF β) to be involved in the aortic aneurysm formation. Losartan, an Angiotensin II type 1 receptor blocker inhibits TGFβ in a mouse model of Marfan syndrome leading to inhibition of aortic growth. The main objective of this trial is to assess whether losartan treatment leads to a clinically relevant decrease of aortic dilatation in adult patients with Marfan syndrome.Methods/Design: COMPARE study (COzaar in Marfan Patients Reduces aortic Enlargement) is an open-label, randomized, controlled trial with blinded end-points. Treatment with losartan will be compared with no additional treatment after 3 years of follow-up. We will enroll 330 patients with MFS who will be randomly assigned to receive losartan or not. Patients taking beta-blockers will continue taking their standard treatment. The primary end-point is the largest change in aortic diameter at any aortic level measured by means of MRI. Secondary end-points are change in mortality, incidence of dissection, elective aortic surgery, aortic volume, aortic stiffness and ventricular function. We will also investigate gene and protein expression change in the skin under losartan therapy and create prediction models for losartan-treatment response and aortic dilatation.Discussion: The COMPARE study will provide important evidence of effects of losartan treatment in adult Marfan patient population. We expect losartan to significantly reduce the occurrence and progression of aortic dilatation. This trial investigates a wide spectrum of clinical, genetic and biochemical effects of losartan aiming to provide further insight in the pathogenesis and treatment of Marfan syndrome.Trial registration: Netherlands Trial Register NTR1423.
UR - http://www.scopus.com/inward/record.url?scp=77649129149&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/1745-6215-11-3
DO - https://doi.org/10.1186/1745-6215-11-3
M3 - Article
C2 - 20067609
SN - 1745-6215
VL - 11
SP - 3
JO - Trials
JF - Trials
IS - 1
M1 - 3
ER -