Pulmonary Hypertension: Intensification and Personalisation of Combination Rx (PHoenix)

NHS Foundation Trust

Status and phase: Enrolling; Phase 4

Conditions: Pulmonary Arterial Hypertension

Treatments: Device: Confirm Rx; Drug: Riociguat; Drug: Selexipag; Device: CardioMEMS pulmonary artery pressure monitor

Study type: Interventional

Funder types: Other

Identifiers

NCT05825417

STH21653

MR/W026279/1 (Other Grant/Funding Number)

325120 (Other Identifier)

Details and patient eligibility

About

The goal of this clinical trial is to evaluate the capacity of implantable/remote technology for early evaluation of drug therapies in patients with pulmonary arterial hypertension (PAH). The main question it aims to answer is whether structured changes in clinical therapy will be detectable using implanted regulatory approved devices. Participants will will be implanted with approved medical devices and will enter into a study of approved drugs to assess physiology, activity and patient reported quality-of-life (QoL) outcomes. Researchers will compare two therapeutic strategies in each individual patient to see if the study design provides enough evidence to personalise drug treatment plans

Full description

In this study, patients established on guideline recommended therapy will be implanted with devices and remote monitoring established. Patients will then enter into a 2x2 crossover study of approved drugs during which standard clinical investigations will be undertaken at baseline and maximal therapy on each drug. The cross-over design will provide multiple increases and decreases of drugs known to alter haemodynamics and 6MWT. The study is powered to detect improvement in right ventricular stroke volume measured by MRI from baseline to maximal therapy for each drug. It will then be established if changes in remote monitored measures provide an early indication of clinical efficacy when compared to the MRI, haemodynamics, NTproBNP and 6MWT made at 12-weeks. Remote measurement of haemodynamics during the two periods of de-escalation will inform understanding of physiology and inform clinical practice. The comparison of the two therapeutic strategies in individual patients in one study will facilitate novel clinical study designs and provide evidence for data-driven personalised medicine in the area.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Able to provide informed consent
• Age 18-80 years
• PAH which is idiopathic, heritable or associated with drugs, toxins or connective tissue disease
• Stable PAH therapeutic regime comprising any combination of ERA and PDE5i for at least 1 month prior to screening (unless unable to tolerate therapy)
• WHO functional class III
• Resting mPAP ≥20 mmHg, pulmonary capillary wedge pressure ≤15 mmHg, pulmonary vascular resistance ≥2 Wood Units measured by right heart catheterisation at time of diagnosis
• 6MWT >50m at entry
• Estimated glomerular filtration rate (eGFR)>30 ml/min/1.73 m² at entry (Appendix C)
• Inadequate treatment response (clinically determined)

Exclusion criteria

• Unable to provide informed consent
• Pregnancy
• Unprovoked pulmonary embolism (at any time)
• Acute infection at time of screening (rescreening is permitted)
• PAH due to human immunodeficiency virus, portal hypertension, schistosomiasis, congenital heart disease
• Pulmonary hypertension due to left heart, lung, thromboembolic or unclear/multifactorial disease (Group II-V)
• Unable to tolerate aspirin or P2Y12 inhibitor
• Hypersensitivity to selexipag or riociguat
• Clinically-significant renal disease (eGFR≤30 ml/min/1.73m2)
• Anaemia (haemoglobin <10 g/dl)
• Left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following: aortic or mitral valve disease greater than mild aortic insufficiency; mild aortic stenosis; mild mitral stenosis; or moderate mitral regurgitation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Arm A (selexipag/riociguat)

Active Comparator group

Description:

Baseline - established PDE/ERA therapy Week 1 - initiate OPA (PDE/ERA/OPA therapy) Weeks 2-12 - uptitration of OPA to maximal therapy (PDE/ERA/OPA therapy) Weeks 13-14 - reduce OPA (PDE/ERA/OPA therapy) Week 15 - washout OPA (PDE/OPA therapy) Week 16 - washout PDE (ERA therapy) Week 17 - initiate sGCS (ERA/sGCS therapy) Weeks 18-27 - uptitration of sGCS to maximal therapy (ERA/sGCS therapy)

Treatment:

Device: CardioMEMS pulmonary artery pressure monitor

Drug: Selexipag

Drug: Riociguat

Device: Confirm Rx

Arm B (riociguat/selexipag)

Active Comparator group

Description:

Baseline - established PDE/ERA therapy Week 1 - washout PDE (ERA therapy only) Week 2 - initiate sGCS (ERA/sGCS therapy) Weeks 3-12 - uptitration of sGCS to maximal therapy (ERA/sGCS therapy) Week 13 - reduce sGCS (ERA/sGCS therapy) Week 14 - reduce and washout sGCS (ERA therapy) Week 15 - initiate PDE (PDE/ERA therapy) Week 16 - initiate OPA (PDE/ERA/OPA therapy) Weeks 17-27 - uptitration of OPA to maximal therapy (PDE/ERA/OPA therapy)

Treatment:

Device: CardioMEMS pulmonary artery pressure monitor

Drug: Selexipag

Drug: Riociguat

Device: Confirm Rx