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

2022. május 17. frissítette: SciPharm SàRL

A Double Blind Controlled Clinical Study to Investigate the Efficacy and Tolerability of Subcutaneous Treprostinil Sodium in Patients With Severe Non-operable Chronic Thromboembolic Pulmonary Hypertension (CTREPH)

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.

A tanulmány áttekintése

Állapot

Befejezve

Körülmények

Beavatkozás / kezelés

Részletes leírás

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.

Tanulmány típusa

Beavatkozó

Beiratkozás (Tényleges)

105

Fázis

  • 3. fázis

Kapcsolatok és helyek

Ez a rész a vizsgálatot végzők elérhetőségeit, valamint a vizsgálat lefolytatásának helyére vonatkozó információkat tartalmazza.

Tanulmányi helyek

  • Ausztria
      • Linz, Ausztria, 4020
        • Krankenhaus der Elisabethinen
      • Vienna, Ausztria
        • Medical University of Vienna AKH - Division Cardiology
  • Csehország
      • Prague, Csehország
        • II. interní klinika Všeobecná fakultní nemocnice
  • Lengyelország
      • Krakow, Lengyelország, 31-202
        • Department of Cardiac and Vascular Diseases Centre for Rare Cardiovascular Diseases John Paul II Hospital
      • Otwock, Lengyelország, 05-400
        • NZOZ Europejskie Centrum Zdrowia Otwock
  • Németország
      • Dresden, Németország
        • Medical University Carl Gustav Carus Medizinische Klinik und Poliklinik I Medizinische Fakultät der Technischen Universität Dresden

Részvételi kritériumok

A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.

Jogosultsági kritériumok

Tanulmányozható életkorok

18 év (Felnőtt, Idősebb felnőtt)

Egészséges önkénteseket fogad

Nem

Tanulmányozható nemek

Összes

Leírás

  1. Subject must be competent to understand the information given in the written informed consent and from the investigator and must sign and date the informed consent prior to any study mandated procedure.
  2. Subject must be at least 18 years of age and can be of any ethnical origin
  3. Women of child bearing potential must be surgically sterile or postmenopausal (amenorrhea for at least 12 months) or using an acceptable form of contraception. Reliable contraception is defined as a method which results in a low failure rate, i.e., less than 1% per year when used correctly such as, implants, injectables, oral contraceptive medications, sexual abstinence, or a vasectomised partner.

  4. Subject must have a current diagnosis of CTEPH, as defined by the following criteria:

    • A test result of perfusion scintigraphy and pulmonary angiography and/or multislice CT not older than 6 months, consistent with the diagnosis CTEPH. In case of recurrent PH after PEA, test results from before the surgery are acceptable if a typical specimen was harvested during PEA substantiating the diagnosis of CTEPH.
    • A right heart catheterization, not older than 6 months, consistent with the diagnosis CTEPH but specifically with a mean pulmonary artery pressure (PAPm) of > 25 mmHg, and a PVR of > 300 dyn.s.cm-5
    • At least three months of effective anticoagulation therapy (without improvement / to exclude subacute pulmonary emboli)

  5. Subject must have CTEPH classified as severe, as defined by the following criteria:

    • An un-encouraged 6MWT distance of between 150 and 400 meters
    • Classification in the WHO/New York Heart Association (NYHA) functional class III or IV

  6. The subject must not be suitable to undergo a PEA and is therefore defined as non-operable, due to at least one of the following reasons:

    • Clot is not accessible
    • Discrepancy between severity of PH and morphologic lesion
    • Subject is not a good surgical candidate for other reasons:

    PVR > 1500 dynes.s.cm-5 Age Comorbidity No functional lung parenchyma

    • Unsuccessful PEA in the past with residual/recurrent CTEPH
    • No consent for PEA given by subject
  7. Subject must be willing and able to follow all study procedures

Exclusion:

  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

Tanulási terv

Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.

Hogyan készül a tanulmány?

Tervezési részletek

  • Elsődleges cél: Kezelés
  • Kiosztás: Véletlenszerűsített
  • Beavatkozó modell: Párhuzamos hozzárendelés
  • Maszkolás: Négyszeres

Fegyverek és beavatkozások

Résztvevő csoport / kar
Beavatkozás / kezelés
Aktív összehasonlító: 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.
Drog: Treprostinil sodium
Kísérleti: 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.
Drog: Treprostinil sodium

Mit mér a tanulmány?

Elsődleges eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Change in 6-minute Walk Test Distance After 24 Weeks
Időkeret: Baseline and 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

Másodlagos eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Number of Participants With Clinical Worsening
Időkeret: 12 weeks and 24 weeks

Clinical worsening defined as a decrease of 6-minute walk test distance of more than 20% from baseline due to Chronic Thromboembolic Pulmonary Hypertension, decrease of New York Heart Association functional class, hospitalization with the requirement for additional Pulmonary Hypertension specific treatment and/or death due to worsening Chronic Thromboembolic Pulmonary Hypertension.

Clinical Worsening was assessed after 12 weeks and 24 weeks, participants experiencing clinical worsening at any time-point are reported.
12 weeks and 24 weeks
Effect on Maximal Borg Score During 6-minutes Walk Test
Időkeret: Baseline and 24 weeks

The Borg scale was used for rating of dyspnea during 6-minutes walk test. The scale is defined from 0 to > 10 (upper bound) (0 = NOTHING AT ALL; 0.5 = VERY VERY SLIGHT (just noticeable); 1 = VERY SLIGHT; 2 = SLIGHT; 3 = MODERATE; 4 = SOMEWHAT SEVERE; 5 = SEVERE; 6-9 = VERY SEVERE; 10 = VERY VERY SEVERE (almost maximum); >10 MAXIMUM).

As can be seen with the scale, the higher scale values represent a worse outcome.

As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 48 patients in low dose group.
Baseline and 24 weeks
Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class
Időkeret: Baseline and 24 weeks

Class I - Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope.

Class II - Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope.

Class III - Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain or near syncope

Class IV - Patients with pulmonary hypertension in the inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.
Baseline and 24 weeks
Effect on Quality of Life by the MINNESOTA Questionnaire
Időkeret: Baseline and 24 weeks

This questionnaire is composed of 21 questions relating to limitations in lifestyle associated with Heart Failure. Respondents use a 5-point scale that ranges from 0 (none) to 5 (too much), with a score of 0 representing no limitation and a score of 5 representing maximum limitation. The change in individual score sum was evaluated and is displayed in the results, with a possible range of 0-105. Higher values indicate more limitations in Quality of Life.

As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 50 patients randomized to high dose group and 46 patients in low dose group.
Baseline and 24 weeks
Effect on N-terminal Pro-BNP Levels
Időkeret: Baseline and 24 weeks

baseline values, assessment after 12 and 24 weeks

As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 46 patients randomized to high dose group and 46 patients in low dose group.
Baseline and 24 weeks
Effect on Hemodynamic Parameter (PVR - Pulmonary Vascular Resistance)
Időkeret: Baseline and 24 weeks

baseline values, assessment after 24 weeks

As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group.
Baseline and 24 weeks
Effect on Hemodynamic Parameter (CI - Cardiac Index)
Időkeret: Baseline and 24 weeks

baseline values, assessment after 24 weeks

As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group.
Baseline and 24 weeks
Effect on Hemodynamic Parameter (CO - Cardiac Output)
Időkeret: Baseline and 24 weeks

baseline values, assessment after 24 weeks

As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group.
Baseline and 24 weeks
Effect on Hemodynamic Parameter (mPAP - Mean Pulmonary Arterial Pressure)
Időkeret: Baseline and 24 weeks

baseline values, assessment after 24 weeks

As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 47 patients randomized to high dose group and 47 patients in low dose group.
Baseline and 24 weeks
Effect on Hemodynamic Parameter (mRap - Mean Right Atrial Pressure)
Időkeret: Baseline and 24 weeks

baseline values, assessment after 24 weeks

As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group.
Baseline and 24 weeks
Effect on Signs & Symptoms of the CTEPH
Időkeret: Baseline and 24 weeks
baseline values, assessment after 24 weeks
Baseline and 24 weeks

Együttműködők és nyomozók

Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.

Szponzor

SciPharm SàRL

Nyomozók

  • Kutatásvezető: Irene Lang, MD, Medical University Vienna

Publikációk és hasznos linkek

A vizsgálattal kapcsolatos információk beviteléért felelős személy önkéntesen bocsátja rendelkezésre ezeket a kiadványokat. Ezek bármiről szólhatnak, ami a tanulmányhoz kapcsolódik.

Általános kiadványok

Tanulmányi rekorddátumok

Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.

Tanulmány főbb dátumok

Tanulmány kezdete

2009. március 1.

Elsődleges befejezés (Tényleges)

2016. november 1.

A tanulmány befejezése (Tényleges)

2021. április 1.

Tanulmányi regisztráció dátumai

Először benyújtva

2011. augusztus 12.

Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak

2011. augusztus 12.

Első közzététel (Becslés)

2011. augusztus 15.

Tanulmányi rekordok frissítései

Utolsó frissítés közzétéve (Tényleges)

2022. június 7.

Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak

2022. május 17.

Utolsó ellenőrzés

2022. május 1.

Több információ

A tanulmányhoz kapcsolódó kifejezések

További vonatkozó MeSH feltételek

Egyéb vizsgálati azonosító számok

  • 116-02

Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .

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