Responsiveness of Exercise Tests in Pulmonary Arterial Hypertension (RESPONS)

Reproducibility and Responsiveness of Exercise Tests in Pulmonary Arterial Hypertension

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Sildenafil; Drug: Sugar Pill

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 4G5
      • Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sildenalfil; 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.	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.; Other Names: Viagra; Revatio
Placebo Comparator: 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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Laval University
• Investigators: Principal Investigator: Steeve Provencher, MD, M.Sc., Laval University

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: July 7, 2011
• First Submitted That Met QC Criteria: July 7, 2011
• First Posted (Estimate): July 11, 2011

Study Record Updates

• Last Update Posted (Estimate): October 4, 2012
• Last Update Submitted That Met QC Criteria: October 3, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Exercise; Pulmonary Hypertension; sildenafil; Pulmonary Arterial Hypertension; Six-minute walk test
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: RESPONS PAH