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

NCT ID: NCT01416636

Last Updated: 2022-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2021-04-30

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.

Detailed Description

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by non-resolving organized thromboembolic obstructing the pulmonary vascular bed. These thrombi are resistant to thrombolytic therapy and chronic plasmatic anticoagulation. An increase in pulmonary vascular resistance (PVR), right ventricular overload, and eventually right ventricular failure ensue.

The treatment of choice for CTEPH is pulmonary endarterectomy (PEA), providing a potential cure for the disease. However, about 50 % of patients are not candidates for surgery, mainly because of distal location of thromboemboli. Despite recent advances in the treatment of pulmonary arterial hypertension (PAH), medical treatments have not been recommended for inoperable CTEPH, because of the concept that a predominantly major vessel obstructive arteriopathy would not be suitable for vasodilators. Furthermore, a major drawback of i.v. prostacyclin therapy is the need for a permanent central venous access that increases the risk of infection (0.22-0.68 per patient per year), thrombosis and new major vessel thromboembolism.

Conditions

Non-operable Chronic Thromboembolic Pulmonary Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treprostinil sodium low dose - Arm I

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.

Group Type: ACTIVE_COMPARATOR

Treprostinil sodium

Intervention Type: DRUG

Treprostinil sodium high dose - Arm II

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.

Group Type: EXPERIMENTAL

Treprostinil sodium

Intervention Type: DRUG

Interventions

Treprostinil sodium

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

1. Subject with any form of pulmonary arterial hypertension or any disease known to cause PAH (WHO Group I)

2. Subjects with a total lung capacity (TLC) of < 70% predicted or a forced expiratory volume/forced vital capacity (FEV1/FVC < 50%)

3. Subject who received any prostanoids, within the 30 days before screening or be scheduled to receive prostanoids during the course of the study

4. Subject with a new type of chronic therapy (a different category of vasodilator or diuretic) for PAH added within the last month, except anticoagulants

5. Subject with an increased risk for hemorrhage or stroke or with a major cardiovascular event during the past 6 months.

6. Unstable subjects for any reason (according to the investigators discretion)

7. 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

8. Subject with a known intolerance to any drug relevant for this trial, especially to Treprostinil sodium or prostanoids

9. Subject with a history or suspicion of non compliance

10. Subject who has any musculoskeletal disease or any other disease that would limit ambulation

11. 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

12. Female who is considering pregnancy or who is pregnant and/or lactating

13. Subject who is an investigator or any other team member involved directly or indirectly in the conduct of the clinical study.

14. Subject who is an inmate of a psychiatric ward, prison or is suspected not to be able to give consent of his free will

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SciPharm SàRL

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Irene Lang, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University Vienna

Locations

Krankenhaus der Elisabethinen

Linz, , Austria

Medical University of Vienna AKH - Division Cardiology

Vienna, , Austria

II. interní klinika Všeobecná fakultní nemocnice

Prague, , Czechia

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

Dresden, , Germany

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

Krakow, , Poland

NZOZ Europejskie Centrum Zdrowia Otwock

Otwock, , Poland

Countries

Austria; Czechia; Germany; Poland

References

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.

Reference Type: BACKGROUND

PMID: 8205686 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15194182 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15249497 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12446266 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30477763 (View on PubMed)

Other Identifiers

116-02

Identifier Type: -

Identifier Source: org_study_id