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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by University of Calgary.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Actelion
Information provided by:
University of Calgary
ClinicalTrials.gov Identifier:
NCT01247116
First received: November 23, 2010
Last updated: NA
Last verified: November 2010
History: No changes posted
  Purpose

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
Hypertension, Pulmonary

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • 6 minute walk test distance [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 6 minute walk test distance [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Echocardiographic parameters [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Hemodynamics [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Quality of Life as measured by CAMPHOR questionnaire [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: December 2009
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
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.
  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
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.

Criteria

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%
  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: NCT01247116

Contacts
Contact: Naushad Hirani, MD 403-943-4723 nhirani@ucalgary.ca
Contact: Jean Marks, RN 403-943-4723 jean.marks@albertahealthservices.ca

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

No publications provided

Responsible Party: Naushad Hirani, Clinical Assistant Professor, University of Calgary
ClinicalTrials.gov Identifier: NCT01247116     History of Changes
Other Study ID Numbers: BSC-UOC-2009
Study First Received: November 23, 2010
Last Updated: November 23, 2010
Health Authority: Canada: Health Canada

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

ClinicalTrials.gov processed this record on August 20, 2014