COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Sildenafil to Tadalafil in Pulmonary Arterial Hypertension (SITAR) (SITAR)

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: NCT01043627
Recruitment Status : Completed
First Posted : January 7, 2010
Last Update Posted : November 5, 2012
United Therapeutics
Information provided by:
Mayo Clinic

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

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 Some patients receive up to five 20 mg Revatio (sildenafil for PH) tablets tid, increasing cost fivefold (RPFrantz, unpublished data).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

Layout table for study information
Study Type : Observational
Actual Enrollment : 100 participants
Observational Model: Case-Only
Official Title: Sildenafil to Tadalafil in Pulmonary Arterial Hypertension (SITAR)
Study Start Date : December 2009
Actual Primary Completion Date : December 2011
Actual Study Completion Date : December 2011

Primary Outcome Measures :
  1. Describe tolerability of transition from sildenafil to tadalafil for treatment of pulmonary arterial hypertension (PAH). [ Time Frame: 12/2011 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Compare 6 minute walk distance before and 3 months (range12-16 weeks) after transition. [ Time Frame: 12/2011 ]
  4. Compare World Health Organization (WHO) functional class before and 3 months (range 12-16 weeks) after transition. [ Time Frame: 12/2011 ]
  5. 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 ]
  6. Describe methods for transition from sildenafil to tadalafil for treatment of PAH. [ Time Frame: 12/2011 ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
WHO Group I PAH patients being transitioned from sildenafil to tadalafil therapy.

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

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): NCT01043627

Layout table for location information
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
Layout table for investigator information
Principal Investigator: Robert P Frantz, MD Mayo Clinic
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Robert Frantz MD, Mayo Clinic Identifier: NCT01043627    
Other Study ID Numbers: 09-004590
First Posted: January 7, 2010    Key Record Dates
Last Update Posted: November 5, 2012
Last Verified: November 2012
Additional relevant MeSH terms:
Layout table for MeSH terms
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases