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Responsiveness of Exercise Tests in Pulmonary Arterial Hypertension (RESPONS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vincent Mainguy, Laval University
ClinicalTrials.gov Identifier:
NCT01391104
First received: July 7, 2011
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention
Pulmonary Arterial Hypertension
Drug: Sildenafil
Drug: Sugar Pill

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Reproducibility and Responsiveness of Exercise Tests in Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • 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. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • To assess the efficacy of a combination therapy in pulmonary arterial hypertension (PAH). [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    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.

  • To measure the physiological parameters induced by five different exercise tests in pulmonary arterial hypertension (PAH) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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).


Enrollment: 22
Study Start Date: April 2009
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Revatio
  • Viagra
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01391104

Locations
Canada, Quebec
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ)
Québec, Quebec, Canada, G1V 4G5
Sponsors and Collaborators
Laval University
Investigators
Principal Investigator: Steeve Provencher, MD, M.Sc. Laval University
  More Information

No publications provided

Responsible Party: Vincent Mainguy, Doctorant, Laval University
ClinicalTrials.gov Identifier: NCT01391104     History of Changes
Other Study ID Numbers: RESPONS PAH
Study First Received: July 7, 2011
Last Updated: October 3, 2012
Health Authority: Canada: Ethics Review Committee

Keywords provided by Laval University:
Pulmonary Hypertension
Pulmonary Arterial Hypertension
Exercise
Six-minute walk test
sildenafil

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Sildenafil
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on November 19, 2014