Responsiveness of Exercise Tests in Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

— RESPONS  

Official title:

Reproducibility and Responsiveness of Exercise Tests in Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01391104
• Other study ID #: RESPONS PAH
• Status: Completed
• Phase: N/A
• First received: July 7, 2011
• Last updated: October 3, 2012
• Start date: April 2009
• Est. completion date: November 2011

Study information

• Verified date: October 2012
• Source: Laval University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

Pulmonary arterial hypertension (PAH) is characterized by the progressive increase in pulmonary vascular resistance leading to shortness of breath and exercise intolerance. Exercise capacity has been used as the primary endpoint in most recent randomized controlled trials evaluating PAH-specific therapies as it correlates with functional class and survival in PAH. Exercise test is commonly assessed by the six-minute walk test (6MWT). However, there is commonly some discrepancy between significant clinical improvement and minor changes (generally <10% from baseline) in 6WMT following therapy. Because important clinical decisions are based on patients' functional capacity, a reproducible and sensitive exercise test is needed in PAH. The aim of this study was to compare the reproducibility and the responsiveness of the 6MWT, the endurance shuttle walk test (ESWT) and the cycle endurance test (CET) following pharmacological therapy in this disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• WHO functional class II or III

• Idiopathic PAH, familial PAH, or associated PAH due to connective tissue disease patients

• Mean pulmonary artery pressure =25 mmHg at rest

• Pulmonary capillary wedge pressure =15 mmHg

Exclusion Criteria:

• Prior use of phosphodiesterase type-5 inhibitors

• Unstable clinical condition over the last 4 months

• Recent syncope

• WHO functional class IV

• Left ventricular ejection fraction <40%

• Restrictive or obstructive lung disease

• Intrinsic musculoskeletal abnormality precluding exercise testing

• Patients with a pacemaker

• Treatment with systemic corticosteroids

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Sildenafil
Sildenafil citrate is a phosphodiesterase type-5 inhibitor. Patients will be assigned to sildenafil (20 mg tid) or placebo per os for 28 days in a randomized, double-blind manner. After a four-week wash-out period, patients will then be crossed over to the alternate therapy for the next 28 days.
• Sugar Pill
Patients will be assigned to sildenafil (20 mg tid) or placebo per os for 28 days in a randomized, double-blind manner. After a four-week wash-out period, patients will then be crossed over to the alternate therapy for the next 28 days.

Locations

Country	Name	City	State
Canada	Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ)	Québec	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Laval University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare the reproducibility and the responsiveness of the 6MWT, the endurance shuttle walk test (ESWT) and the cycle endurance test (CET) following pharmacological therapy in PAH.	After completing the 6MWT, the ESWT and the CET in a randomized order, patients will then be randomized to sildenafil (20mg tid) or placebo in a double-blind manner for 28 days. The three exercise tests will then be repeated. After a four-week of wash-out period, patients will repeat the three exercise test and then be crossed over to the alternate therapy for the next 28 days. The same experiments will be repeated after this period. The reproducibility of each exercise test will be assessed following placebo. The responsiveness of each exercise test will be assessed following sildenafil.	3 months	No
Secondary	To assess the efficacy of a combination therapy in pulmonary arterial hypertension (PAH).	Sildenafil will be added to the baseline therapy for one month (20mg tid). The efficacy of this combined therapy will be assessed by three different exercise tests and by a quality of life questionnaire.	1 month	No
Secondary	To measure the physiological parameters induced by five different exercise tests in pulmonary arterial hypertension (PAH)	Within one week, PAH patients will performed five different exercise tests. During each test, a portable telemetric system (Oxycon, Jaegger, Germany) will be used to assess the respiratory cardiovascular adaptations. Symptoms of leg fatigue and dyspnea will be assessed using the Borg scale. Quadriceps fatigability will be assessed by volitional and non-volitional (twitch force, TWq) measurements of the quadriceps strength before and immediately after each test (Magstim Co. Ltd., Whitland, Dyfed, Wales, UK).	2 weeks	No