Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other
      hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase
      type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who
      have demonstrated a sub-optimal response to PDE-5i monotherapy.

      The study was originally designed as a 2-arm, double-blind, randomized study in which
      patients received ambrisentan or placebo for 24 weeks, and then received ambrisentan blinded
      to dose for 24 weeks. With Protocol Amendment 2 (12 June, 2009), the study was switched to
      single-arm, open-label treatment, and all patients remaining in the placebo arm were switched
      to open-label ambrisentan treatment. Patients who enrolled after Amendment 2 all received
      open-label ambrisentan.
    

Detailed description: 
      The primary objective of this study is to evaluate the change from baseline in pulmonary
      vascular resistance (PVR), and other hemodynamic parameters, following the addition of
      ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects
      with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to
      PDE-5i monotherapy.

      The secondary objectives of this study are to evaluate the change from baseline in other
      clinical measures of PAH following the addition of ambrisentan to background PDE-5i therapy
      in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy.

      The safety and tolerability of ambrisentan/PDE-5i combination therapy will be evaluated
      throughout the study. In addition, long-term efficacy will be examined.
    

Intervention name(s): Ambrisentan; Placebo; Sildenafil; Tadalafil
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Ambrisentan was administered orally once daily; dose level was 5 mg for the first 4 weeks, followed by 10 mg for the remainder of the study; ambrisentan was supplied as 5-mg and 10-mg tablets.; Placebo to match ambrisentan was administered orally once daily.; Sildenafil was administered at the dose previously established for each subject (20-100 mg) orally three times daily. Sildenafil was supplied as 20-mg tablets, or formulated as sildenafil citrate in 25-, 50-, or 100-mg tablets.; Tadalafil was administered at the dose previously established for each subject (not to exceed 40 mg per day) orally once daily. Tadalafil was supplied as 20-mg tablets.
Other intervention name(s): Letairis; Revatio; Viagra; Cialis; Adcirca
Intervention MeSH terms: Ambrisentan; Sildenafil Citrate; Tadalafil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ambrisentan; PAH; combination therapy; phosphodiesterase type-5 inhibitor (PDE-5i); cardiovascular; endothelin receptor antagonist; ERA