Bosentan for Mild Pulmonary Vascular Disease in Asd Patients.

NCT01218607 | Completed Phase 3 DMC

• 1 other identifier: UZL-S52480
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Volume overload due to left-to-right shunting in patients with atrial septal defect type secundum causes pulmonary vascular disease over a long period of time. Pulmonary vascular resistance can be assessed non-invasively using bicycle stress echocardiography. By measuring cardiac output and pulmonary artery pressures at different stages of exercise, a pressure-output plot can be obtained. The slope of the pressure-output plot reflects pulmonary vascular resistance. In patients undergoing ASD repair after the age of 40 years, pulmonary vascular resistance was higher when compared to age-matched controls, indicating the presence of mild pulmonary vascular disease. Bosentan has been shown to decrease pulmonary vascular resistance. The investigators hypothesize that in patients with an ASD type secundum, who underwent ASD repair after the age of 40 years, administration of bosentan decreases pulmonary vascular resistance as assessed by bicycle stress echocardiography.

Conditions

Heart Septal Defects, Atrial

Keywords

Heart Septal Defects, Atrial; Pulmonary Circulation; Ventricular Function, Right; Echocardiography, Stress; Ergometry; Tissue Doppler Imaging

Outcome Measures

Primary Outcomes (1)

• Pulmonary vascular resistance

  Pulmonary vascular resistance can be measured using bicycle stress echocardiography by estimating the slope of a pressure-flow plot using linear regression analysis.

  16 weeks

Secondary Outcomes (3)

• Peak oxygen consumption

  16 weeks

• Right ventricular function

  16 weeks

• Liver function abnormalities

  4, 8,12 and16 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Active

ACTIVE COMPARATOR

Drug: Bosentan

Interventions

Bosentan DRUG

Treatment will be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily for 12 weeks.

Also known as: Bosentan = Tracleer

Active

Placebo DRUG

Placebo will be taken twice daily for 16 weeks

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent by patient prior to initiation of any study-mandated procedure.
• Male or female patients \> 40 years with atrial septal defect type secundum and \> 40 years of age at the time of repair
• Women of childbearing potential must have a negative pre-treatment pregnancy test and must use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination.
• Women not of childbearing potential are defined as postmenopausal (amenorrhea for at least 1 year), or documented surgically or naturally sterile.

You may not qualify if:

• Pregnancy or lactation
• Women of child-bearing age who are sexually active without practising reliable methods of contraception
• Any disease or impairment that, in the opinion of the investigator, excludes a subject from participation
• Substance abuse (alcohol, medicines, drugs)
• Other medical, psychological or social circumstances that would adversely affect a patient's ability to participate adequately in the study or increase the risk to the patient or others in the case of participation
• Insufficient compliance
• Subjects who are not able to perform cardiopulmonary exercise testing
• Impairment of organic function (renal, hepatic)
• Arterial hypotension (systolic blood pressure \< 85 mmHg)
• Anaemia (Hb\< 10 g/dl)
• Decompensated symptomatic polycythemia
• Thrombocytopenia (\< 50000/µl)
• Significant valvular diseases, other than tricuspid or pulmonary regurgitation
• Chronic lung disease or total lung capacity \< 80% of predicted value
• History of significant pulmonary embolism

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospitals Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

MeSH Terms

Conditions

Heart Septal Defects, Atrial

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Heart Septal Defects; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Werner Budts, MD, PhD

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: October 8, 2010
• First Posted: October 11, 2010
• Study Start: October 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: March 5, 2014

Record last verified: 2014-03

Locations

BE (1)