Study to investigate the effect of riociguat on right heart size and function in pulmonary hypertensio

Phase 1

• Conditions: MedDRA version: 20.0Level: HLTClassification code 10037401Term: Pulmonary hypertensionsSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]; Symptomatic pulmonary arterial hypertension with a mean pulmonary artery pressure >20 mmHg and pulmonary vascular resistance =2 Wood Units, pulmonary arterial wedge pressure =15 mmHg (Group I / Nice Clinical Classification of Pulmonary Hypertension (PH)) or CTEPH (Group IV) with hemodynamics as stated above defined as inoperable measured at least 3 months after start of full anticoagulation or with persisting or recurrent PH after pulmonary endarterectomy at least 6 months after surgery

• Registration Number: EUCTR2020-005462-34-DE
• Lead Sponsor: Thoraxklinik Heidelberg gGmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-25
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1.=18 years of age at time of inclusion.
2.Male and female patients with symptomatic PAH with a mean pulmonary artery pressure (mPAP) >20 mmHg and pulmonary vascular resistance (PVR) =2 Wood Units (WU), pulmonary arterial wedge pressure (PAWP) =15 mmHg (Group I / Nice Clinical Classification of Pulmonary Hypertension) or CTEPH (Group IV / Nice Clinical Classification of Pulmonary Hypertension) defined as inoperable measured at least 3 months after start of full anticoagulation and mPAP >20 mmHg and PVR =2 WU, PAWP =15 mmHg; or with persisting or recurrent PH after pulmonary endarterectomy (mean pulmonary artery pressure >20 mmHg and PVR =2 WU, PAWP =15 mmHg measured at least 6 months after surgery (acc. to Simonneau et al. 2018).
3.Treatment naïve patients (with respect to PAH specific medication) and patients pre-treated with an endothelin receptor antagonist or a prostacyclin analogue, pre-treated for 2 months before screening at most (according to upfront combination treatment).*
4.*Pre-treated patients need to be stable on endothelin receptor antagonists or prostacyclin treatment for at least two weeks prior to Visit 1. Stable” is defined as no change in the type of endothelin receptor antagonists or prostacyclin analogue and the respective daily dose.
5.A patient may also be enrolled, if a persisting phosphodiesterase type 5 (PDE-5) inhibitor treatment (pre-treated for 2 months before screening at most) with or without combination treatment with an endothelin receptor antagonist or prostacyclin analogue is to be switched to riociguat by clinical indication.
6.Unspecific treatments which may also be used for the treatment of PH such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. However, treatment with anticoagulants (if indicated) must have been started at least 1 month before visit 1.
7.RHC results must not be older than 6 months at screening (will be considered as baseline values) and must have been measured in the participating centre under standardized conditions (refer to the study specific Swan Ganz catheterization manual). If the respective measurements have not been performed in context with the patient’s regular diagnostic workup, they have to be performed as a part of the study during the pre-study phase (after the patient signed the informed consent).
8.Women without childbearing potential defined as postmenopausal women aged 50 years or older, women with bilateral tubal ligation, women with bilateral ovariectomy, and women with hysterectomy can be included in the study. Women with childbearing potential can only be included in the study if a serological pregnancy test is negative and a combination of condoms with a safe and highly effective contraception method (hormonal contraception with implants or combined oral contraceptives, certain IUDs) is used.
9.Patients who are able to understand and follow instructions and who are able to participate in the study for the entire period.
10.Patients must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1.Pregnant women, or breast-feeding women, or women with childbearing potential not using a combination of condoms and a safe and highly effective contraception method (hormonal contraception with implants or combined oral contraceptives, certain IUDs).
2.Patients with PH specific treatment >2 months before screening.
3.Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator.
4.Patients with underlying medical disorders with an anticipated life expectancy below 2 years (e.g. active cancer disease with localized and/or metastasized tumour mass).
5.Patients with a history of severe allergies or multiple drug allergies.
6.Patients with hypersensitivity to the investigational drug or any of the excipients.
7.Patients unable to perform a valid 6MWD test (e.g. orthopaedic disease, peripheral artery occlusive disease, which affects the patient´s ability to walk).
8.The following specific medications for concomitant treatment of PH or medications which may exert a pharmacodynamic interaction with the study drug are not allowed:
a)Parenteral prostacyclin analogues
b)Specific (e.g. sildenafil or tadalafil) or unspecific phosphodiesterase inhibitors (e.g. dipyridamole, theophylline)
c)NO donors (e.g. Nitrates)
9.Pulmonary diseases exclusions
a)Moderate to severe bronchial asthma or COPD (Forced Expiratory Volume <60% predicted).
b)Severe restrictive lung disease (Total Lung Capacity < 70% predicted).
c)Severe congenital abnormalities of the lungs, thorax, and diaphragm.
d)Clinical or radiological evidence of Pulmonary-Veno-Occlusive Disease (PVOD) or Pulmonary Capillary Haemangiomatosis (PCH) or PH and idiopathic interstitial pneumonia (PH-IIP)
10.Cardiovascular exclusions:
a)Uncontrolled arterial hypertension (systolic blood pressure >180 mmHg and /or diastolic blood pressure >110 mmHg).
b)Systolic blood pressure <95 mmHg.
c)Left heart failure with an ejection fraction less than 40%.
d)Pulmonary venous hypertension with pulmonary arterial wedge pressure >15 mmHg.
e)Hypertrophic obstructive cardiomyopathy.
f)Severe proven or suspected coronary artery disease according to investigators opinion (patients with Canadian Cardiovascular Society Angina Classification class 2-4, and/or requiring nitrates, and/or myocardial infarction within the last 3 months before Visit 1).
g)Clinical evidence of symptomatic atherosclerotic disease (e.g. peripheral artery disease with reduced walking distance, history of stroke with persistent neurological deficit etc).
11.Exclusions related to disorders in organ function:
a)Clinically relevant hepatic dysfunction indicated by:
i.bilirubin >2 times upper limit normal
ii.and / or hepatic transaminases >3 times upper limit normal
iii.and / or signs of severe hepatic insufficiency (e.g. impaired albumin synthesis with an albumin < 32 g/l, hepatic encephalopathy > grade 1a: West Haven Criteria of Altered Mental Status In Hepatic Encephalopathy)
b)Renal insufficiency (glomerular filtration rate <30 ml/min e.g. calculated based on the Cockcroft formula).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified