Riociguat in patients with operable CTEPH prior to PEA
Research type
Research Study
Full title
A Phase 2, Randomised, Double-Blind, Placebo-Controlled, Multicentre, Prospective Study to Assess Efficacy of Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy With High Preoperative Pulmonary Vascular Resistance
IRAS ID
236317
Contact name
Joanna Pepke-Zaba
Contact email
Sponsor organisation
International CTEPH Association (ICA)
Eudract number
2017-001121-40
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 4 months, 17 days
Research summary
Chronic thromboembolic pulmonary disease is an important cause of severe pulmonary hypertension (PH) and is associated with significant morbidity and mortality. It is estimated that 3.8% of patients suffering from an acute pulmonary embolus will develop chronic thromboembolic pulmonary hypertension (CTEPH). This is characterised by obstruction of the pulmonary vasculature by residual organised thrombi and concomitant small vessel disease, leading to increased pulmonary vascular resistance (PVR), progressive PH, and right ventricular failure.
In some patients, PH persists after pulmonary endarterectomy (PEA) despite adequate clearance of the chronic thromboembolic material. Patients with untreated CTEPH are likely to develop progressive disease and have a high risk of death due to right heart failure. The first step in the management of CTEPH is the initiation of anticoagulant therapy, which has limited efficacy in this indication. In addition, drugs such as bosentan, prostacyclin, and iloprost have been used with varying efficacy.
Riociguat is the first of a new class of drugs, the soluble guanylate cyclase (sGC) stimulators. Different sGC stimulators have shown beneficial effects in different models of acute and chronic PH.
Riociguat exerts strong effects on pulmonary haemodynamics and exercise capacity in patients with PH, and is approved for the treatment of cardiovascular diseases, especially PH.
This study will investigate if pre-PEA treatment with Riociguat in operable CTEPH can improve preoperative pulmonary haemodynamics and key clinical outcomes after PEA. The current study is a randomised, double-blind, placebo-controlled, multicentre, prospective study of a 3-month treatment period followed by a 6-month safety follow-up period in patients with operable CTEPH with high preoperative PVR.
Study procedures will include vital signs, physical examinations, ECG, urine/blood samples, haemodynamic assessment, surgical evaluation of thromboembolic material during PEA, in addition to assessment of perioperative findings, length of hospital stay and time on mechanical ventilation post-PEA.REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
18/YH/0330
Date of REC Opinion
17 Sep 2018
REC opinion
Favourable Opinion