First-line Bosentan and Sildenafil Combination Therapy for Pulmonary Arterial Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01247116
Recruitment Status : Unknown
Verified November 2010 by University of Calgary.
Recruitment status was:  Recruiting
First Posted : November 24, 2010
Last Update Posted : November 24, 2010
Information provided by:
University of Calgary

Brief Summary:
The purpose of this study is to evaluate the strategy of initiating double oral combination therapy with bosentan and sildenafil at the time of diagnosis of pulmonary arterial hypertension (PAH) in a preliminary way.

Condition or disease
Hypertension, Pulmonary

Detailed Description:

Current treatment paradigms for PAH suggest adopting goals of therapy with relatively objective parameters such as 6 minute walk distance to determine when to add a second oral agent (1). This often entails observing deterioration in the patient on a single agent before instituting the second one. This strategy could be problematic, as patients may never recover the function lost due to progressive PAH (2). In addition, given the malignant nature of the clinical course of PAH in many cases and the nature of the underlying proliferative vasculopathy, some have argued that altering this paradigm to resemble that used in cancer chemotherapy may be more appropriate (3). That is, "induction" therapy at diagnosis with multiple agents followed by a maintenance phase of treatment might offer significant benefits to the patient.

This open-label pilot study is the first to investigate the potential efficacy and safety of a first-line combination strategy in consecutive patients with PAH in contrast to the "add-on" strategy for combination therapy. It will serve as the basis on which to consider larger, multicenter investigations of this strategy.

  1. Hoeper M, et al. Eur Respir J. 2005 Nov;26(5):858-63.
  2. Halpern SD, et al. Proc Am Thorac Soc. 2008 Jul 15;5(5):631-5.
  3. Provencher S, et al. Chest. 2005 Dec;128(6 Suppl):622S-628S.

Study Type : Observational
Estimated Enrollment : 15 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: First-line Bosentan and Sildenafil Combination Therapy for Pulmonary Arterial Hypertension: A Safety and Efficacy Pilot Study
Study Start Date : December 2009
Estimated Primary Completion Date : December 2012

Primary Outcome Measures :
  1. 6 minute walk test distance [ Time Frame: 4 months ]

Secondary Outcome Measures :
  1. 6 minute walk test distance [ Time Frame: 12 months ]
  2. Echocardiographic parameters [ Time Frame: 4 months ]
  3. Hemodynamics [ Time Frame: 4 months ]
  4. Quality of Life as measured by CAMPHOR questionnaire [ Time Frame: 4 months ]

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Consecutive patients with idiopathic pulmonary arterial hypertension (IPAH) or PAH associated with connective tissue disease that are naive to PAH targeted therapies will be enrolled.

Inclusion Criteria:

  • Patients with symptomatic Functional Class III PAH in the following categories: Idiopathic (IPAH), Familial (FPAH), Associated with connective tissue disease, Associated with drugs or toxins
  • PAH diagnosed by right heart catheterization, defined as: mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg, PVR > 3 mmHg/l/min (Wood units) or > 240 dyn sec cm-5, pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg
  • Baseline 6 MWT distance > 150 and < 450 m

Exclusion Criteria:

  • Treatment with ERAs other than bosentan;
  • Treatment with PDE5 inhibitors other than sildenafil;
  • Treatment with any prostanoid;
  • PAH associated with thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders and splenectomy; valvular disease with valvular lesions to be excluded by echocardiogram within 2 years prior to randomization
  • Restrictive lung disease: total lung capacity (TLC) < 60% of normal predicted value;
  • Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) < 50%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01247116

Contact: Naushad Hirani, MD 403-943-4723
Contact: Jean Marks, RN 403-943-4723

Canada, Alberta
University of Calgary, Peter Lougheed Hospital Recruiting
Calgary, Alberta, Canada, T1Y 6J4
Sponsors and Collaborators
University of Calgary
Principal Investigator: Naushad Hirani, MD University of Calgary

Responsible Party: Naushad Hirani, Clinical Assistant Professor, University of Calgary Identifier: NCT01247116     History of Changes
Other Study ID Numbers: BSC-UOC-2009
First Posted: November 24, 2010    Key Record Dates
Last Update Posted: November 24, 2010
Last Verified: November 2010

Additional relevant MeSH terms:
Familial Primary Pulmonary Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Antihypertensive Agents
Endothelin Receptor Antagonists