Initial Triple Therapy Including Parenteral Treprostinil vs Initial Double Oral Therapy in PAH Group I Patients

NCT06317805 | Recruiting Phase 4

• 2 other identifiers: TREV1-10P.4012023-504351-26-01
• Study Type: interventional
• Target: 110
• Locations: 10 countries
• Sites: 19

Brief Summary

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

intermediate-high risk; intermediate-low risk with severe hemodynamic impairment

Outcome Measures

Primary Outcomes (1)

• 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.

  between week 12 and week 48 from baseline (BL)

Secondary Outcomes (23)

• Change in hemodynamic parameters by means of right heart catheterization (RHC) - PVR

  at week 24 from baseline (BL)

• Change in hemodynamic parameters by means of right heart catheterization (RHC) - mPAP

  at week 24 from baseline (BL)

• Change in hemodynamic parameters by means of right heart catheterization (RHC) - mRAP

  at week 24 from baseline (BL)

• Change in hemodynamic parameters by means of right heart catheterization (RHC) - CI

  at week 24 from baseline (BL)

• Change in hemodynamic parameters by means of right heart catheterization (RHC) - CO

  at week 24 from baseline (BL)

Other Outcomes (1)

• Safety outcomes:

  between baseline and week 48

Study Arms (2)

Initial triple therapy

EXPERIMENTAL

Assigned treatment: double oral (background therapy consisting of 1 endothelin receptor antagonist ERA and 1 phosphodiesterase type-5 inhibitor PDE-5i) with subcutaneous (SC)/intravenous (IV) treprostinil on top

Drug: Generic treprostinil sodium + Standard of Care (Double Oral); Drug: Standard of Care - Double Oral

• Initial double therapy

ACTIVE COMPARATOR

double oral (background therapy consisting of 1 endothelin receptor antagonist ERA and 1 phosphodiesterase type-5 inhibitor PDE-5i)

Drug: Standard of Care - Double Oral

Interventions

Generic treprostinil sodium + Standard of Care (Double Oral) DRUG

Treprostinil (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.

Also known as: Trisuva, Tresuvi, Treposa, Treprostinil Orpha-Devel, Treprostinil Amomed, Treprostinil OrPha, Treposuvi

Initial triple therapy

Standard of Care - Double Oral DRUG

All 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)

Initial triple therapy; • Initial double therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to any trial-mandated procedure
• Male or female ≥ 18 and ≤ 70 years of age
• Symptomatic treatment-naïve PAH patients (group I) with confirmed diagnosis of one of the following subgroups:
• idiopathic pulmonary arterial hypertension (IPAH)
• hereditary pulmonary arterial hypertension (HPAH)
• Drug and toxin-induced pulmonary arterial hypertension (DPAH)
• PAH associated with Connective Tissue Disease
• PAH with corrected congenital heart disease 4. Intermediate-high risk patients rated acc. the simplified four-strata risk-assessment tool or intermediate-low risk with severe hemodynamic impairment as defined in current PH guidelines i.e., mean right atrial pressure (RAP) ≥ 20 mmHg, cardiac index (CI) \< 2.0 L/min, stroke volume index (SVI) \< 31 mL/m2 and/or pulmonary vascular resistance (PVR) ≥ 12 WU
• Right Heart Catheterization (RHC) meeting all the following criteria:
• Mean pulmonary arterial pressure (mPAP) \> 20 mmHg
• Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg
• PVR \> 2 Wood Units
• Women of childbearing potential must not be pregnant or lactating, must perform regular pregnancy tests, if sexually active, agrees to continue to use reliable method(s) of contraception until study completion

You may not qualify if:

• PAH patients (group I) belonging to one of the following subgroups:
• Schistosomiasis
• HIV infection
• Portal hypertension
• Diffuse systemic sclerosis
• Uncorrected congenital heart disease including uncorrected systemic-to-pulmonary shunts
• Any PAH-specific drug therapy in the past 3 months
• Patients responding to vasoreactivity testing with calcium channel blockers (CCB)
• Post-capillary PH and left heart disease
• Known or suspected pulmonary veno-occlusive disease (PVOD)
• Any PH due to lung disease
• Any disorder of the respiratory system expressed by Diffusing Capacity of Lung for Carbon Monoxide (DLCO) \<40% and a noticeable imaging result (e.g., CT) and (Total Lung Capacity) TLC \<60% and (Forced Expiratory Volume) FEV1 \<70% by plethysmography (a pulmonary function test)
• Patients with need of ambulatory or long-term oxygen therapy
• Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) \> 480 msec at screening
• Body mass index (BMI) \> 35 (kg/m2)

Sponsors & Collaborators

• AOP Orphan Pharmaceuticals AG: lead
• ANOVA CRO s.r.o.: collaborator
• PharmaLex Belgium: collaborator
• Aixial s.r.o.: collaborator
• GCP-Service International Ltd. & Co. KG: collaborator

Study Sites (19)

Ordensklinikum Linz

Linz, Austria

RECRUITING

Medical University Vienna

Vienna, Austria

RECRUITING

Fakultní Nemocnice Olomouc

Olomouc, Czechia

NOT YET RECRUITING

Všeobecná fakultní nemocnice v Praze

Prague, Czechia

NOT YET RECRUITING

Hôpital Bicêtre-- Assistance Publique Hopitaux de Paris

Paris, France

NOT YET RECRUITING

Hôpitaux Universitaires de Strasbourg

Strasbourg, France

NOT YET RECRUITING

DRK Kliniken Berlin Westend

Berlin, Germany

NOT YET RECRUITING

University Hospital Carl Gustav Carus of Technical University Dresden

Dresden, Germany

NOT YET RECRUITING

Universitätsmedizin Greifswald

Greifswald, Germany

NOT YET RECRUITING

Gottsegen National Cardiovascular lnstitute

Budapest, Hungary

NOT YET RECRUITING

Medical University of Szeged

Szeged, Hungary

NOT YET RECRUITING

Sapienza University of Rome

Rome, Italy

RECRUITING

John Paul II Hospital Krakow

Krakow, Poland

NOT YET RECRUITING

Fryderyk Chopin Hospital in European Health Centre Otwock

Otwock, Poland

NOT YET RECRUITING

Centro Hospitalar Lisboa Norte - Santa Maria University Hospital

Lisbon, Portugal

NOT YET RECRUITING

Emergency Institute for Cardiovascular Diseases Prof. Dr. C.C.Iliescu

Bucharest, Romania

NOT YET RECRUITING

Emergency Clinical County Hospital of Targu Mures

Târgu Mureş, Romania

NOT YET RECRUITING

Hospital Clinic of Barcelona

Barcelona, Spain

NOT YET RECRUITING

Hospital Ramon y Cajal

Madrid, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Clinical Project Manager

CONTACT

+43676 3464650; tripletre@aoporphan.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, two-arm, open-label, low-interventional, phase IV, multi-centre clinical trial comparing efficacy and safety of initial triple therapy including parenteral treprostinil to initial double oral therapy (background therapy with endothelin receptor antagonist - ERA and phosphodiesterase type-5 inhibitor - PDE-5i) by proportion of patients achieving low risk status according to the simplified four-strata risk-assessment tool from week 24 up to 48 weeks in 110 (55/group) treatment-naïve adult intermediate-high risk or intermediate-low risk patients with severe hemodynamic impairment with pulmonary arterial hypertension (PAH) (group I).

Study Record Dates

• First Submitted: February 20, 2024
• First Posted: March 19, 2024
• Study Start: December 6, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: March 19, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); FR (2); RO (2); CZ (2); ES (2); PL (2); DE (3); HU (2); AU (2); PT (1)