Pulmonary Hypertension: Intensification and Personalisation of Combination Rx

NCT05825417 | Recruiting Phase 4 DMC FDA Drug FDA Device

• 3 other identifiers: STH21653MR/W026279/1325120
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pulmonary Arterial Hypertension

Keywords

remote monitoring; therapeutic development; personalised medicine

Outcome Measures

Primary Outcomes (1)

• Right Ventricular Stroke Volume (RVSV) flow on each therapy measured by MRI RSVS (flow) on each therapy measured by MRI

  This provides a robust, objective assessment of clinical efficacy which, if met, will mean that a change in therapy has provided a clinically meaningful change in physiology

  Baseline to Week 12

Secondary Outcomes (23)

• Haemodynamics - Total Pulmonary Resistance (TPR)

  From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks

• Haemodynamics - mean Pulmonary Artery Pressure (mPAP)

  From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks

• Haemodynamics - Cardiac Output (CO)

  From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks

• Haemodynamics - Cardiac Index

  From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks

• Haemodynamics - Stroke Volume (SV)

  From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks

Study Arms (2)

Arm A (selexipag/riociguat)

ACTIVE COMPARATOR

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)

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

Arm B (riociguat/selexipag)

ACTIVE COMPARATOR

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)

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

Interventions

Selexipag DRUG

If Arm A - Up-titration to maximum tolerated dose followed by de-escalation If Arm B - Up-titration to maximum tolerated dose followed by observation, modification or transition at discretion of responsible care team where necessary.

Also known as: Uptravi, oral prostacyclin IP receptor agonist (OPA)

Arm A (selexipag/riociguat); Arm B (riociguat/selexipag)

Riociguat DRUG

If Arm A - Up-titration to maximum tolerated dose followed by de-escalation If Arm B - Up-titration to maximum tolerated dose followed by observation, modification or transition at discretion of responsible care team where necessary.

Also known as: Adempas, soluble guanylate cyclase stimulator (sGCS)

Arm A (selexipag/riociguat); Arm B (riociguat/selexipag)

CardioMEMS pulmonary artery pressure monitor DEVICE

Implantation and remote monitoring established with patient initiated daily readings

Arm A (selexipag/riociguat); Arm B (riociguat/selexipag)

Confirm Rx DEVICE

Implantation and remote monitoring established with automated daily readings / downloads

Arm A (selexipag/riociguat); Arm B (riociguat/selexipag)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• MWT \>50m at entry
• Estimated glomerular filtration rate (eGFR)\>30 ml/min/1.73 m² at entry (Appendix C)
• Inadequate treatment response (clinically determined)

You may not qualify if:

• 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

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• University of Glasgow: collaborator
• University of Sheffield: collaborator
• University of Newcastle Upon-Tyne: collaborator
• University of Cambridge: collaborator

Study Sites (1)

Sheffield Teaching Hospitals NHS FT

Sheffield, S10 2JF, United Kingdom

RECRUITING

Related Publications (1)

• Swift AJ, Wilson F, Cogliano M, Kendall L, Alandejani F, Alabed S, Hughes P, Shahin Y, Saunders L, Oram C, Capener D, Rothman A, Garg P, Johns C, Austin M, Macdonald A, Pickworth J, Hickey P, Condliffe R, Cahn A, Lawrie A, Wild JM, Kiely DG. Repeatability and sensitivity to change of non-invasive end points in PAH: the RESPIRE study. Thorax. 2021 Oct;76(10):1032-1035. doi: 10.1136/thoraxjnl-2020-216078. Epub 2021 Feb 25.

  PMID: 33632769 BACKGROUND

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

selexipag; riociguat

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Alexander Rothman, MD / PhD

  University of Sheffield

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Dick, PhD

CONTACT

+44 (0) 114 2159550; jennifer.dick@sheffield.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2x2 crossover study in which the effects of adding an oral drug targeting the prostacyclin pathway and the switching of PDE5i to sGCS will be examined following 12-weeks on treatment.

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 24, 2023
• Study Start: June 14, 2023
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: December 3, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)