Sildenafil to Tadalafil in Pulmonary Arterial Hypertension (SITAR)

NCT ID: NCT01043627

Last Updated: 2012-11-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2011-12-31

Brief Summary

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

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 Some patients receive up to five 20 mg Revatio (sildenafil for PH) tablets tid, increasing cost fivefold (RPFrantz, unpublished data).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.

Conditions

Pulmonary Arterial Hypertension

Study Design

• Observational Model Type: CASE_ONLY

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United Therapeutics

INDUSTRY

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mayo Clinic

Principal Investigators

Robert P Frantz, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Robert Bourge MD

Birmingham, Alabama, United States

Ron Oudiz

Torrance, California, United States

Charles Burger MD

Jacksonville, Florida, United States

Countries

United States

References

Frantz RP, Durst L, Burger CD, Oudiz RJ, Bourge RC, Franco V, Waxman AB, McDevitt S, Walker S. Conversion from sildenafil to tadalafil: results from the sildenafil to tadalafil in pulmonary arterial hypertension (SITAR) study. J Cardiovasc Pharmacol Ther. 2014 Nov;19(6):550-7. doi: 10.1177/1074248414528066. Epub 2014 Apr 17.

Reference Type: DERIVED

PMID: 24742768 (View on PubMed)

Other Identifiers

09-004590

Identifier Type: -

Identifier Source: org_study_id