Comparison of Medical Therapies in Marfan Syndrome.

Effects of Atenolol, Perindopril and Verapamil on Haemodynamic and Vascular Function in Marfan Syndrome - A Randomised Double-Blind Crossover Trial

The investigators are looking at the different impacts of atenolol, verapamil and perindopril on large artery and lv function in marfan syndrome. It is a double-blind, randomised cross-over trial.

Study Overview

• Status: Completed
• Conditions: Marfan Syndrome
• Intervention / Treatment: Drug: Atenolol; Drug: VERAPAMIL; Drug: Perindopril

Detailed Description

The investigators recruited 21 patients with confirmed diagnosis of Marfan syndrome from two centres. The investigators performed radial artery applanation tonometry and pulse wave analysis to derive central aortic pressure and haemodynamic indexes pre-and post administering Atenolol 75mg, Perindopril 4mg and Verapamil 240mgs each for four weeks with a two week wash-out between medications. All patients underwent detailed functional and anatomical echocardiographic assessments at each visit.

Inclusion criteria were ages 16-60 years with no treatment or β-blocker or other monotherapy only for Marfan syndrome. Patients with previous aortic dissection or aortic surgery, severe valvular regurgitation, aortic diameter at the sinotubular junction ≥ 5.0cm, contraindications to specific drug treatment, e.g. asthma and β-blocker, or those who were pregnant or at risk of pregnancy were excluded.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Cardiff, United Kingdom, CF14 4XN
    • Wales Heart Research Institute, Cardiff University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 16-60 years old with no treatment or β-blocker or other monotherapy only for Marfan syndrome

Exclusion Criteria:

• Previous aortic dissection or aortic surgery
• Severe valvular regurgitation
• Aortic diameter at the sinotubular junction ≥ 5.0cm
• Contraindications to specific drug treatment, e.g. asthma and β-blocker
• Those who were pregnant or at risk of pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ATENOLOL; ATENOLOL 75MG FOR 4 WEEKS	Drug: Atenolol
Active Comparator: VERAPAMIL; 240MG VERAPAML FOR 4 WEEKS	Drug: VERAPAMIL; 240 MG SR
Active Comparator: PERINDOPRIL; 4MG PERINDOPRIL FOR 4 WEEKS	Drug: Perindopril; 4 MG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CENTRAL ARTERIAL PRESSURE	CENTRAL ARTERIAL PRESSURE MEASURED BY APPLANATION TONOMETRY	18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LARGE ARTERIAL STIFFNESS INDICES	MEASURED BY ECHO AND BY PULSE WAVE VELOCITY/ANALYSIS BY APPLANATION TONOMETRY	18 WEEKS
LV Function	GLOBAL AND REGIONAL MARKERS BY ECHO	18 WEEKS

Collaborators and Investigators

• Sponsor: Cardiff University

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: February 11, 2011
• First Submitted That Met QC Criteria: February 11, 2011
• First Posted (Estimate): February 14, 2011

Study Record Updates

• Last Update Posted (Estimate): February 14, 2011
• Last Update Submitted That Met QC Criteria: February 11, 2011
• Last Verified: January 1, 2006

More Information

Terms related to this study

• Keywords: verapamil; atenolol; LV function; perindopril; Marfan Syndrome; Large arterial function; central arterial pressure
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Bone Diseases, Developmental; Limb Deformities, Congenital; Syndrome; Marfan Syndrome; Arachnodactyly; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Protease Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin-Converting Enzyme Inhibitors; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Verapamil; Perindopril; Atenolol
• Other Study ID Numbers: SPONCU101; 2005-000749-13 (EudraCT Number)