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Pulmonary Hypertension: Intensification and Personalisation of Combination Rx

NCT ID: NCT05825417

Last Updated: 2024-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-14

Study Completion Date

2026-01-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Pulmonary Arterial Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (selexipag/riociguat)

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)

Group Type ACTIVE_COMPARATOR

Selexipag

Intervention Type 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.

Riociguat

Intervention Type 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.

CardioMEMS pulmonary artery pressure monitor

Intervention Type DEVICE

Implantation and remote monitoring established with patient initiated daily readings

Confirm Rx

Intervention Type DEVICE

Implantation and remote monitoring established with automated daily readings / downloads

Arm B (riociguat/selexipag)

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)

Group Type ACTIVE_COMPARATOR

Selexipag

Intervention Type 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.

Riociguat

Intervention Type 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.

CardioMEMS pulmonary artery pressure monitor

Intervention Type DEVICE

Implantation and remote monitoring established with patient initiated daily readings

Confirm Rx

Intervention Type DEVICE

Implantation and remote monitoring established with automated daily readings / downloads

Interventions

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Selexipag

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.

Intervention Type DRUG

Riociguat

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.

Intervention Type DRUG

CardioMEMS pulmonary artery pressure monitor

Implantation and remote monitoring established with patient initiated daily readings

Intervention Type DEVICE

Confirm Rx

Implantation and remote monitoring established with automated daily readings / downloads

Intervention Type DEVICE

Other Intervention Names

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Uptravi oral prostacyclin IP receptor agonist (OPA) Adempas soluble guanylate cyclase stimulator (sGCS)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Glasgow

OTHER

Sponsor Role collaborator

University of Sheffield

OTHER

Sponsor Role collaborator

University of Newcastle Upon-Tyne

OTHER

Sponsor Role collaborator

University of Cambridge

OTHER

Sponsor Role collaborator

Sheffield Teaching Hospitals NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alexander Rothman, MD / PhD

Role: PRINCIPAL_INVESTIGATOR

University of Sheffield

Locations

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Sheffield Teaching Hospitals NHS FT

Sheffield, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Jennifer Dick, PhD

Role: CONTACT

[email protected]
+44 (0) 114 2159550

Facility Contacts

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Alex Rothman

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 33632769 (View on PubMed)

Other Identifiers

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MR/W026279/1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

325120

Identifier Type: OTHER

Identifier Source: secondary_id

STH21653

Identifier Type: -

Identifier Source: org_study_id