TripleTRE investigates the effect of initial triple combination therapy (oral endothelin receptor antagonist (ERA) + oral phosphodiesterase tyüe-5 inhibitor (PDE-5i) + parenteral treprostinil) compared to double oral therapy (oral ERA + oral PDE-5i) in pulmonary arterial hypertension (PAH) patients (group I) with intermediate-high risk or patients with intermediate-low risk with severe hemodynamic impairment at baseline in a prospective, randomized, unblinded setting with scope of increasing evidence for optimization of therapy concepts in PAH.
The effect of initial triple combination therapy vs initial double oral therapy (standard of care (SoC)) will be measured by primary endpoint: (non)response to the assigned treatment.
Signed informed consent prior to any trial-mandated procedure
Male or female ≥ 18 and ≤ 70 years of age
idiopathic pulmonary arterial hypertension (IPAH)
hereditary pulmonary arterial hypertension (HPAH)
Schistosomiasis
HIV infection
Portal hypertension
Diffuse systemic sclerosis
Parallel
Generic treprostinil sodium + Standard of Care (Double Oral)
DrugTreprostinil (prostacyclin analogue) solution for continuous subcutaneous (SC) or intravenous (IV) infusion (1 mg/ml; 2.5 mg/ml; 5 mg/ml; 10 mg/ml in 10 mL glass vial) will be administered by an infusion pump system and up-titrated to ≥40 ng/kg/min or to the maximum tolerated dose within 24 weeks. Further up-titration shall be performed until trial completion according to the discretion of the investigator.
Standard of Care - Double Oral
DrugAll patients will receive standard of care double oral background treatment consisting of one Phosphodiesterase type 5 inhibitor (i.e., tadalafil or sildenafil) and one Endothelin Receptor Antagonist (i.e. ambrisentan, bosentan or macitentan)
Patients achieving (non-)response status to the assigned treatment in terms of achievement of low-risk status
1. Therapy-responder: achievement of low-risk status between week 24 and week 48 2. Therapy-non-responder: 1. PH related deterioration to high-risk status, lung transplantation or death between week 12 and week 48 and/or 2. additional medication or change of initial PH specific medication due to unsatisfactory efficacy between week 12 and week 48 and/or 3. low risk status not achieved up to week 48 Risk status is assessed with the simplified four-strata risk-assessment tool as per PH guidelines.
Change in hemodynamic parameters by means of right heart catheterization (RHC) - PVR
Pulmonary Vascular Resistance (PVR) measured in WU
Change in hemodynamic parameters by means of right heart catheterization (RHC) - mPAP
Mean pulmonary arterial pressure (mPAP) measured in mmHg
Change in hemodynamic parameters by means of right heart catheterization (RHC) - mRAP
Mean right atrial pressure (mRAP) measured in mmHg
Change in hemodynamic parameters by means of right heart catheterization (RHC) - CI
Cardiac index (CI) measured in liters per minute per square meter
Safety outcomes:
1. Number of Adverse events (AE) and Adverse reactions (ADR) 2. Number of Serious Adverse events (SAE) and Serious Adverse Drug Reactions (SADR) 3. Number of Suspected unexpected serious adverse reactions (SUSAR)
Click on the lead sponsor to view all of their trials.
AOP Orphan Pharmaceuticals AG
Lead sponsor
ANOVA CRO s.r.o.
Collaborator
PharmaLex Belgium
Collaborator
Aixial s.r.o.
Collaborator
GCP-Service International Ltd. & Co. KG
Collaborator
