Efficacy and Tolerability of Subcutaneously Administered Treprostinil Sodium in Patients With Severe (Non-operable) Chronic Thromboembolic Pulmonary Hypertension (CTREPH)

NCT01416636 | Completed Phase 3 Results

• 1 other identifier: 116-02
• Study Type: interventional
• Target: 105
• Locations: 4 countries
• Sites: 6

Brief Summary

The primary purpose of this study is to determine the effect on six-minute walking test (6MWT) distance after 24 weeks treatment with subcutaneous (SC) Treprostinil Sodium in patients with Severe (inoperable) Chronic Thromboembolic Pulmonary Hypertension.

Conditions

Non-operable Chronic Thromboembolic Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in 6-minute Walk Test Distance After 24 Weeks

  To determine the effect of subcutaneous Treprostinil sodium on 6-minute walk test distance after 24 weeks in patients with severe non-operable chronic thromboembolic pulmonary hypertension severe (inoperable) Chronic Thromboembolic Pulmonary Hypertension Time frame of the 6-minute walk test: The 6-minute walk test was conducted at the following visits: * baseline (day 1) * Visit 6 (day 168) In case of missing values, Last-Observation-Carried-Forward imputation method was used. In such cases values documented at Visit 4 (day84) were used.

  Baseline and 24 weeks

Secondary Outcomes (11)

• Number of Participants With Clinical Worsening

  12 weeks and 24 weeks

• Effect on Maximal Borg Score During 6-minutes Walk Test

  Baseline and 24 weeks

• Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class

  Baseline and 24 weeks

• Effect on Quality of Life by the MINNESOTA Questionnaire

  Baseline and 24 weeks

• Effect on N-terminal Pro-BNP Levels

  Baseline and 24 weeks

Study Arms (2)

Treprostinil sodium low dose - Arm I

ACTIVE COMPARATOR

Arm I (low dose): Subject was treated with a low dose of Treprostinil sodium. Dose was escalated to an approximate target dose of 3 ng/kg/min after the first 12 weeks and was kept stable for another 12 weeks. Due to the predefined infusion rate setting schedule an interim dose of up to 6 ng/kg/min could be reached for few days at the end of the phases 1,2 and 3. This depended on the patient's exact weight and is caused by the limited infusion rate setting possibility of the infusion pump.

Drug: Treprostinil sodium

Treprostinil sodium high dose - Arm II

EXPERIMENTAL

Subject was treated with a low dose of Treprostinil sodium. Dose was escalated to an approximate target dose of 3 ng/kg/min after the first 12 weeks and kept stable for another 12 weeks. Due to the predefined infusion rate setting schedule an interim dose of up to 6 ng/kg/min could be reached for few days at the end of the phases 1,2 and 3. This depended on the patient's exact weight and is caused by the limited infusion rate setting possibility of the infusion pump.

Drug: Treprostinil sodium

Interventions

Treprostinil sodium DRUG

Treprostinil sodium high dose - Arm II; Treprostinil sodium low dose - Arm I

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Subject with any form of pulmonary arterial hypertension or any disease known to cause PAH (WHO Group I)
• Subjects with a total lung capacity (TLC) of \< 70% predicted or a forced expiratory volume/forced vital capacity (FEV1/FVC \< 50%)
• Subject who received any prostanoids, within the 30 days before screening or be scheduled to receive prostanoids during the course of the study
• Subject with a new type of chronic therapy (a different category of vasodilator or diuretic) for PAH added within the last month, except anticoagulants
• Subject with an increased risk for hemorrhage or stroke or with a major cardiovascular event during the past 6 months.
• Unstable subjects for any reason (according to the investigators discretion)
• Subject who received any investigational medication within 30 days prior to the screening visit of this study or be scheduled to receive another investigational drug during the course of this study
• Subject with a known intolerance to any drug relevant for this trial, especially to Treprostinil sodium or prostanoids
• Subject with a history or suspicion of non compliance
• Subject who has any musculoskeletal disease or any other disease that would limit ambulation
• Subject with other cardiovascular, liver, renal, hematologic, gastrointestinal immunologic, endocrine, metabolic, or central nervous system disease that, in the opinion of the investigator, may adversely affect the safety of the subject and /or efficacy of the study drug or limit the lifespan of the subject
• Female who is considering pregnancy or who is pregnant and/or lactating
• Subject who is an investigator or any other team member involved directly or indirectly in the conduct of the clinical study.
• Subject who is an inmate of a psychiatric ward, prison or is suspected not to be able to give consent of his free will

Sponsors & Collaborators

• SciPharm SàRL: lead

Study Sites (6)

Krankenhaus der Elisabethinen

Linz, 4020, Austria

Location

Medical University of Vienna AKH - Division Cardiology

Vienna, Austria

Location

II. interní klinika Všeobecná fakultní nemocnice

Prague, Czechia

Location

Medical University Carl Gustav Carus Medizinische Klinik und Poliklinik I Medizinische Fakultät der Technischen Universität Dresden

Dresden, Germany

Location

Department of Cardiac and Vascular Diseases Centre for Rare Cardiovascular Diseases John Paul II Hospital

Krakow, 31-202, Poland

Location

NZOZ Europejskie Centrum Zdrowia Otwock

Otwock, 05-400, Poland

Location

Related Publications (5)

• Lang IM, Marsh JJ, Olman MA, Moser KM, Loskutoff DJ, Schleef RR. Expression of type 1 plasminogen activator inhibitor in chronic pulmonary thromboemboli. Circulation. 1994 Jun;89(6):2715-21. doi: 10.1161/01.cir.89.6.2715.

  PMID: 8205686 BACKGROUND

• Klepetko W, Mayer E, Sandoval J, Trulock EP, Vachiery JL, Dartevelle P, Pepke-Zaba J, Jamieson SW, Lang I, Corris P. Interventional and surgical modalities of treatment for pulmonary arterial hypertension. J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):73S-80S. doi: 10.1016/j.jacc.2004.02.039.

  PMID: 15194182 BACKGROUND

• McLaughlin VV, Presberg KW, Doyle RL, Abman SH, McCrory DC, Fortin T, Ahearn G; American College of Chest Physicians. Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004 Jul;126(1 Suppl):78S-92S. doi: 10.1378/chest.126.1_suppl.78S.

  PMID: 15249497 BACKGROUND

• Kuhn KP, Byrne DW, Arbogast PG, Doyle TP, Loyd JE, Robbins IM. Outcome in 91 consecutive patients with pulmonary arterial hypertension receiving epoprostenol. Am J Respir Crit Care Med. 2003 Feb 15;167(4):580-6. doi: 10.1164/rccm.200204-333OC. Epub 2002 Nov 21.

  PMID: 12446266 BACKGROUND

• Sadushi-Kolici R, Jansa P, Kopec G, Torbicki A, Skoro-Sajer N, Campean IA, Halank M, Simkova I, Karlocai K, Steringer-Mascherbauer R, Samarzija M, Salobir B, Klepetko W, Lindner J, Lang IM. Subcutaneous treprostinil for the treatment of severe non-operable chronic thromboembolic pulmonary hypertension (CTREPH): a double-blind, phase 3, randomised controlled trial. Lancet Respir Med. 2019 Mar;7(3):239-248. doi: 10.1016/S2213-2600(18)30367-9. Epub 2018 Nov 23.

  PMID: 30477763 DERIVED

MeSH Terms

Interventions

treprostinil

Results Point of Contact

• Title: Bianca Tan
• Organization: SciPharm SàRL

b.tan@scipharm.eu

Study Officials

• Irene Lang, MD

  Medical University Vienna

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2011
• First Posted: August 15, 2011
• Study Start: March 1, 2009
• Primary Completion: November 1, 2016
• Study Completion: April 1, 2021
• Last Updated: June 7, 2022
• Results First Posted: June 10, 2019

Record last verified: 2022-05

Locations

CZ (1); DE (1); PL (2); AU (2)