Sildenafil to Tadalafil in Pulmonary Arterial Hypertension (SITAR)

This study has been completed.
Sponsor:
Collaborator:
United Therapeutics
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01043627
First received: January 6, 2010
Last updated: November 2, 2012
Last verified: November 2012
  Purpose

Assess tolerability, transition methods and clinical effects of transition from sildenafil (Revatio) to tadalafil (Adcirca) for treatment of pulmonary arterial hypertension.


Condition
Pulmonary Arterial Hypertension

Study Type: Observational
Study Design: Observational Model: Case-Only
Official Title: Sildenafil to Tadalafil in Pulmonary Arterial Hypertension (SITAR)

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Describe tolerability of transition from sildenafil to tadalafil for treatment of pulmonary arterial hypertension (PAH). [ Time Frame: 12/2011 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare Treatment Satisfaction Questionnaire for Medication (TSQM) before and 30 days (range 30-45 days) after transition and 3 months (range 12-16 weeks) after transition. [ Time Frame: 12/2011 ] [ Designated as safety issue: No ]
  • Compare N-terminal pro-BNP (NBNP) or brain natriuretic peptide (BNP) levels before and 3 months (range 12-16 weeks) after transition. [ Time Frame: 12/2011 ] [ Designated as safety issue: No ]
  • Compare 6 minute walk distance before and 3 months (range12-16 weeks) after transition. [ Time Frame: 12/2011 ] [ Designated as safety issue: No ]
  • Compare World Health Organization (WHO) functional class before and 3 months (range 12-16 weeks) after transition. [ Time Frame: 12/2011 ] [ Designated as safety issue: No ]
  • Compare echo parameters (estimated cardiac output, TAPSE, Tei index) before and 6 months (range 4-8 months) after transition. If sufficient data is available at 3 month followup, this will be compared as well. [ Time Frame: 12/2011 ] [ Designated as safety issue: No ]
  • Describe methods for transition from sildenafil to tadalafil for treatment of PAH. [ Time Frame: 12/2011 ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: December 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Detailed Description:

Sildenafil (Revatio) received approval for treatment of pulmonary arterial hypertension based upon the results of the SUPER1 study that randomized patients to sildenafil 20, 40 or 80 mg tid or matching placebo. 1 For the open label extension study, all patients received 80 mg tid. Following analysis of the data, the FDA approved 20 mg tid, indicating that "higher doses are not recommended" (Revatio PDR package insert). Although there was no significant difference between dosing groups in the overall cohort with regard to 6 minute walk, patients with idiopathic PAH did have a greater hemodynamic effect at the 80 mg tid dose, raising the possibility that the maximum approved dose was not the maximally hemodynamically effective dose for at least some patient subsets. This has resulted in a confusing situation with some clinicians treating patients with sildenafil doses substantially above the FDA recommended dose, which creates issues of cost and insurance coverage. Some patients receive up to five 20 mg Revatio (sildenafil for PH) tablets tid, increasing cost fivefold (RPFrantz, unpublished data).

Tadalafil (Adcirca) received FDA approval for treatment of PAH in May 2009, and will be available for this indication in August 2009. The pivotal Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) study randomized 405 patients with WHO group I PAH who were either treatment naïve or on background therapy with bosentan, to receive placebo, 2.5, 10, 20 or 40 mg daily.2 A dose response was observed, with 40 mg daily meeting the primary endpoint of improvement in 6 minute walk at 16 weeks (placebo-corrected treatment effect 33 m, p < 0.01), while the composite time to clinical worsening endpoint was also met. The FDA approved dose of tadalafil for PAH is 40 mg (two 20 mg tablets) daily. 20 mg daily improved median walk distance nearly as much as the 40 mg dose, but just missed the required p value based upon the statistical plan. The PHIRST trial is the first placebo controlled trial to document an incremental benefit of phosphodiesterase-5 inhibition in patients already receiving an endothelin receptor antagonist. This has important implications for the concept of combination therapy in PAH.

Since tadalafil can be administered once daily, and the cost of the therapy is less than for sildenafil, it is anticipated that many patients will transition from sildenafil to tadalafil. The goal of this prospective and retrospective study is to gather observational data regarding how that switch is made, tolerability of the switch, and, to the extent possible with this methodology, assess clinical effects of the switch.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

WHO Group I PAH patients being transitioned from sildenafil to tadalafil therapy.

Criteria

Inclusion Criteria:

  • Treatment for PAH with sildenafil at a dose of 20mg tid or greater for at least 30 days
  • Clinical decision to convert from sildenafil to tadalafil therapy
  • Patient consents to study participation (for patients who have already transitioned from sildenafil to tadalafil therapy prior to study initiation or identification of the patient, if the patient has provided consent for use of their medical record for research, retrospective review of the transition process will be performed. When possible, these patients will be approached about prospective data collection for the study if the transition occurred less than 3 months prior to consideration of prospective study participation)

Exclusion Criteria:

  • Non-group I PAH
  • Age less than 18
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01043627

Locations
United States, Alabama
Robert Bourge MD
Birmingham, Alabama, United States, 35294
United States, California
Ron Oudiz
Torrance, California, United States, 90502
United States, Florida
Charles Burger MD
Jacksonville, Florida, United States, 32224
Sponsors and Collaborators
Mayo Clinic
United Therapeutics
Investigators
Principal Investigator: Robert P Frantz, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Robert Frantz MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01043627     History of Changes
Other Study ID Numbers: 09-004590
Study First Received: January 6, 2010
Last Updated: November 2, 2012
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on April 17, 2014