Pulmonary Arterial HypertensionPhase 4PHoenixNCT05825417

Pulmonary Hypertension: Intensification and Personalisation of Combination Rx

A Phase 4 study testing Selexipag, Riociguat and CardioMEMS pulmonary artery pressure monitor in people with Pulmonary Arterial Hypertension, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Pulmonary Arterial Hypertension
What is being tested?: Selexipag, Riociguat and CardioMEMS pulmonary artery pressure monitor
Type of treatment: Pill or oral medicine, Injection or infusion, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 70 participants
Where: 1 siteUnited Kingdom
Study dates: 14 Jun 2023to Jan 2028
Phase: Phase 4
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 23Show fewer

6MWT >50m at entry
Estimated glomerular filtration rate (eGFR)>30 ml/min/1.73 m² at entry (Appendix C)
Inadequate treatment response (clinically determined)
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 doses of background PAH therapy for at least 30 days prior to screening with inadequate treatment response (clinically determined)
WHO FC II or III despite treatment with diuretics
Field Walk Distance thresholds: 6MWT >50m at entry or ISWT >180m or equivalent ESWD
Patients of childbearing potential must:
Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting the study.
Agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of sotatercept
If sexually active, have used and agree to use, highly effective contraception without interruption for at least 28 days prior to starting sotatercept, during the study and for 16 weeks (112 days) after discontinuation
Patients of non-childbearing potential must:
Agree to use a condom, defined as a male latex condom or non-latex condom NOT made from natural (animal) membrane (e.g. polyurethane), during sexual contact with a pregnant person of childbearing potential while participating in the study, during dose interruptions and for at least 16 weeks (112 days) following discontinuation of sotatercept
Refrain from donating blood or sperm for the duration of the study and for 112 days after the last dose of sotatercept
Ability to adhere to study visit schedule and comply with all protocol requirements for sotatercept monitoring

Who cannot join

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)

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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
Part 2:
Unable to provide informed consent
Pregnancy or breast feeding
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
Any of the following clinical laboratory defined values at the screening visit.
Platelet count <50 x 109/L
Haemoglobin above gender-specific upper limit of normal as per local laboratory test
eGFr <30mL/min/m2 (as defined by MDRD equation)
serum ALT or AST >3x upper limit of normal
total bilirubin >1.5x upper limit of normal
Currently enrolled in or have completed any other investigational product study within 30 days for small-molecule drugs or within 5 half-lives for biologics prior to the date of signed informed consent
Known allergic reaction to sotatercept (ACE-011) or luspatercept (ACE-536)
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 locations and contacts

1 site in 1 country.

United Kingdom1 site

Sheffield Teaching Hospitals NHS FT
Sheffield, S10 2JF

Other trials in United Kingdom

About this study

Official title: A Multicentre Randomised Cross-over Trial of Disease Specific Therapy in Patients With Pulmonary Arterial Hypertension (PAH) Implanted With Pulmonary Artery Pressure and Cardiac Rhythm Monitoring Devices (CardioMEMS/ConfirmRx)

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.

Read the detailed description

In this study, patients established on guideline recommended therapy will be implanted with devices and remote monitoring established.

Part 1 (Randomised crossover Phase) : Patients will 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.

Part 2 (Extension Phase- Sotatercept):Following completion of Part 1 (or via direct entry for eligible patients in WHO FC II/III on background PAH therapy), patients enter an open-label , single arm extension phase evaluating treatment escalation with sotatercept (Winrevair).Subcutaneous sotatercept will be initiated at a starting dose of 0.3 mg/kg once every 3 weeks and escalated after 3 weeks to a target maintenance dose of 0.7 mg/kg based on clinical response, weight, and safety parameter verification (haematoglobin and platelet counts). Unlike the multi-drug crossover design in Part 1, Part 2 specifically isolates the longitudinal hemodynamic, functional, and quality-of-life (emPHasis-10, EQ-5D-5L) trajectory following the introduction of a novel activin-signaling inhibitor. This phase will establish the rate and velocity of physiological change under single-agent titration to determine whether continuous daily remote metrics can detect early treatment response compared to standard 24-week clinical endpoint assessments.

Conditions: Pulmonary Arterial Hypertension
Being tested: Selexipag, Riociguat, CardioMEMS pulmonary artery pressure monitor, Confirm Rx, Sotatercept
Keywords: remote monitoring, therapeutic development, personalised medicine
Medical subject headings: Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SelexipagDrug
Also called Uptravi, oral prostacyclin IP receptor agonist (OPA)
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.
RiociguatDrug
Also called Adempas, soluble guanylate cyclase stimulator (sGCS)
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 monitorDevice
Implantation and remote monitoring established with patient initiated daily readings
Confirm RxDevice
Implantation and remote monitoring established with automated daily readings / downloads
SotaterceptDrug
Subcutaneous injection of sotatercept administered once every 3 weeks for 24 weeks. Treatment is initiated at a starting dose of 0.3 mg/kg at Week 0 and escalated at Week 3 to a target maintenance dose of 0.7 mg/kg, contingent on body weight, clinical response, and pre-dose safety parameters (haematoglobin and platelet counts). Maintenance dosing at 0.7 mg/kg continues every 3 weeks through Week 21, alongside continuous daily remote hemodynamic and physiological monitoring via implanted CardioMEMS and cardiac rhythm devices.

Study groups in NCT05825417
Study group	Role	What they receive
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) Receives: 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) Receives: Drug: Selexipag; Drug: Riociguat; Device: CardioMEMS pulmonary artery pressure monitor; Device: Confirm Rx
Arm C : Sotatercept	Active comparator	Baseline - established background therapy; initiate sotatercept 0.3 mg/kg Week 3 - evaluate safety parameters (Hb/platelets) \& uptitrate sotatercept to target dose 0.7 mg/kg . Weeks 6, 9, 12, 15, 18, 21 - maintenance sotatercept 0.7 mg/kg every 3 weeks with safety monitoring Week 24 - final maintenance dose and endpoint assessments Receives: Device: CardioMEMS pulmonary artery pressure monitor; Device: Confirm Rx; Drug: Sotatercept

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Baseline to Week 12 of each crossover period
Daily Hemodynamic Detection of Treatment Response During Sotatercept Escalation
Within-patient changes in continuous, remote-monitored Total Pulmonary Resistance (TPR), mean Pulmonary Artery Pressure (mPAP), Cardiac Output (CO), Stroke Volume (SV), and Heart Rate (HR) detected by the CardioMEMS sensor following treatment escalation with sotatercept, correlated with end-of-treatment RVSV measured by cardiac MRI.
Measured: Baseline (Week 0) through Week 24

Secondary outcomes (25)

Haemodynamics - Total Pulmonary Resistance (TPR)
Change in TPR (Woods Units) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
Haemodynamics - mean Pulmonary Artery Pressure (mPAP)
Change in mPAP (mmHg) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
Haemodynamics - Cardiac Output (CO)
Change in CO (L/min) on each therapy to determine clinical efficacy
Measured: Part 1 : From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
Haemodynamics - Cardiac Index
Change in cardiac index (L/min/m^2) on each therapy to determine clinical efficacy
Measured: Part 1 : From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
Haemodynamics - Stroke Volume (SV)
Change in SV (mL) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
Haemodynamics - Heart Rate (HR)
Change in HR (bpm) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
6 Minute Walk Test
Change on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
NTpro-BNP
Change on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
MRI - Right Ventricular Ejection Fraction (RVEF)
RVEF (%) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Right Ventricular End Systolic Volume (RVESV)
RVESV (mL/m^2) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Right Ventricular End Diastolic Volume (RVEDV)
RVEDV (mL/m^2) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Right Ventricular Stroke Volume (RVSV)
RVSV (mL) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Left Ventricular Volume Fraction (LVEF)
LVEF (%) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Left Ventricular End Systolic Volume (LVESV)
LVESV (mL/m^2) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Left Ventricular End Diastolic Volume LVEDV
LVEDV (mL/m^2) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Left Ventricular Stroke Volume (LVSV)
LVSV (mL) on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Left Ventricular Stroke Volume (LVSV) flow
LVSV flow on each therapy to determine clinical efficacy
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
Patient Reported Outcomes (PRO) - Quality of Life (QoL) (EmPHasis-10)
Change of QoL score on each therapy to determine clinical efficacy. This will be done using EmPHasis-10 questionnaire (10 questions using a 0 (poor) - 5 (good) scale)
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
Patient Reported Outcomes (PRO) - Medication Compliance (PHoenix PRO)
Change of medication compliance score on each therapy to determine clinical efficacy. This will be done using PHoenix PRO questionnaire (10 questions using a 0 (poor) - 5 (good) scale)
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks
Patient Reported Outcomes (PRO) - Medication Side Effects
Change of medication side effects on each therapy to determine clinical efficacy. This will be done using PHoenix Medication side effects questionnaires (4 Yes/No or Better/Worse style questions)
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
Patient Reported Outcomes (PRO) - Depression symptoms (GAD-2/7)
Change of depression symptoms on each therapy to determine clinical efficacy. This will be done using the GAD-2/7 questionnaire (2 screening questions to determine if symptoms present. If present, 7 additional questions to determine level of depression using a 0 (not at all) - 3 (nearly every day) scale)
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
Patient Reported Outcomes (PRO) - Anxiety symptoms (PHQ-2/9)
Change of anxiety symptoms on each therapy to determine clinical efficacy. This will be done using the PHQ-2/9 questionnaire (2 screening questions to determine if symptoms present. If present, 9 additional questions to determine level of anxiety using a 0 (not at all) - 3 (nearly every day) scale)
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
WHO functional class
Change on each therapy to determine clinical efficacy. Functional assessment of PAH will be made according to the WHO classification system: Class I - Patients with PAH without limitation of physical activity. Ordinary physical activity does not cause increased dyspnoea or fatigue, chest pain, or near syncope / Class II - Patients with PAH resulting in slight limitation of physical activity. No discomfort at rest. Normal physical activity causes increased dyspnoea or fatigue, chest pain, or near syncope / Class III - Patients with PAH resulting in marked limitation of physical activity. There is no discomfort at rest. Less than ordinary activity causes increased dyspnoea or fatigue, chest pain, or near syncope / Class IV - Patients with PAH with inability to carry out any physical activity without discomfort. Indications of manifest right heart failure. Dyspnoea and/or fatigue may even be present at rest. Discomfort is increased by the least physical activity.
Measured: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
EuroQoL-5D-5L
The EuroQoL-5D-5L is included for future health economic evaluation of sotatercept. (free for non-commercial use
Measured: Part 2 only : From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
PHoenix UTAUT questionnaire
Evaluation of remote monitoring technology and devices.
Measured: Part 1 only: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Jun 2023Jan 2028

First posted24 Apr 2023
Study start14 Jun 2023
Primary completionJan 2028 (estimated)
Study completionJan 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Part 1 : 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. Part 2 :Following completion of Part 1 (or via direct entry for eligible patients), participants transition into a single-arm, treatment-escalation extension phase. All participants receive subcutaneous sotatercept initiated at a dose of 0.3 mg/kg every 3 weeks and escalated to a target maintenance dose of 0.7 mg/kg based on clinical response, body weight, and safety monitoring . Continuous daily remote hemodynamic and physiological monitoring is maintained throughout the 24-week extension period.
Masking: None (open label)
Enrolment: 70 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05825417
Sponsor's protocol ID: STH21653
Other IDs: MR/W026279/1, MISP 102663, 325120
Acronym: PHoenix
Status last verified: Jun 2026
First submitted: 24 Mar 2023
Last updated: 7 Aug 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: Yes
Individual data sharing: No: Research samples will be transferred to the Sheffield Biorepository with no identifiable personal data. Data will be collected and hosted and processed by University of Oxford (data supplier). Authorised data originators include, but are not limited to PIs and delegated staff; Participants; and Core Imaging Laboratory. The trial manager will lead the data verification process. Remote monitoring data will be managed through the Merlin.net system (Device supplier - Abbott). Pseudonymised data will then be transferred, held, analysed and archived securely at the University of Glasgow (processor). Data will also be transferred to the University of Sheffield and Newcastle University (processor) for study analysis. The University of Sheffield shall own all right, title and interest in and to all of the University of Sheffield Data. For the purposes of the Data Protection Legislation, Sheffield Teaching Hospitals (sponsor) is the Data Controller.

Publications

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.
PubMed 33632769

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicentre Randomised Cross-over Trial of Disease Specific Therapy in Patients With Pulmonary Arterial Hypertension (PAH) Implanted With Pulmonary Artery Pressure and Cardiac Rhythm Monitoring Devices (CardioMEMS/ConfirmRx)
ClinicalTrials.gov ID: NCT05825417
Acronym / sponsor ID: PHoenix / STH21653
Conditions: Pulmonary Arterial Hypertension
Keywords: remote monitoring, therapeutic development, personalised medicine
Phase: Phase 4
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 70 participants (estimated)
Lead sponsor: Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
Collaborators: University of Glasgow, University of Sheffield, University of Newcastle Upon-Tyne, University of Cambridge
Study start: 14 Jun 2023 (actual)
Primary completion: Jan 2028 (estimated)
Study completion: Jan 2028 (estimated)
First posted: 24 Apr 2023 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

In this study, patients established on guideline recommended therapy will be implanted with devices and remote monitoring established.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3
Model description: Part 1 : 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. Part 2 :Following completion of Part 1 (or via direct entry for eligible patients), participants transition into a single-arm, treatment-escalation extension phase. All participants receive subcutaneous sotatercept initiated at a dose of 0.3 mg/kg every 3 weeks and escalated to a target maintenance dose of 0.7 mg/kg based on clinical response, body weight, and safety monitoring . Continuous daily remote hemodynamic and physiological monitoring is maintained throughout the 24-week extension period.

Arm	Type	Receives
Arm A (selexipag/riociguat)	Active comparator	Drug: Selexipag, Drug: Riociguat, Device: CardioMEMS pulmonary artery pressure monitor, Device: Confirm RxBaseline - 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)
Arm B (riociguat/selexipag)	Active comparator	Drug: Selexipag, Drug: Riociguat, Device: CardioMEMS pulmonary artery pressure monitor, Device: Confirm RxBaseline - 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)
Arm C : Sotatercept	Active comparator	Device: CardioMEMS pulmonary artery pressure monitor, Device: Confirm Rx, Drug: SotaterceptBaseline - established background therapy; initiate sotatercept 0.3 mg/kg Week 3 - evaluate safety parameters (Hb/platelets) \& uptitrate sotatercept to target dose 0.7 mg/kg . Weeks 6, 9, 12, 15, 18, 21 - maintenance sotatercept 0.7 mg/kg every 3 weeks with safety monitoring Week 24 - final maintenance dose and endpoint assessments

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (23 listed)

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

Key exclusion criteria (28 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SelexipagAlso: Uptravi, oral prostacyclin IP receptor agonist (OPA)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.	Drug	Arm A (selexipag/riociguat), Arm B (riociguat/selexipag)
RiociguatAlso: Adempas, soluble guanylate cyclase stimulator (sGCS)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.	Drug	Arm A (selexipag/riociguat), Arm B (riociguat/selexipag)
CardioMEMS pulmonary artery pressure monitorImplantation and remote monitoring established with patient initiated daily readings	Device	Arm A (selexipag/riociguat), Arm B (riociguat/selexipag), Arm C : Sotatercept
Confirm RxImplantation and remote monitoring established with automated daily readings / downloads	Device	Arm A (selexipag/riociguat), Arm B (riociguat/selexipag), Arm C : Sotatercept
SotaterceptSubcutaneous injection of sotatercept administered once every 3 weeks for 24 weeks. Treatment is initiated at a starting dose of 0.3 mg/kg at Week 0 and escalated at Week 3 to a target maintenance dose of 0.7 mg/kg, contingent on body weight, clinical response, and pre-dose safety parameters (haematoglobin and platelet counts). Maintenance dosing at 0.7 mg/kg continues every 3 weeks through Week 21, alongside continuous daily remote hemodynamic and physiological monitoring via implanted CardioMEMS and cardiac rhythm devices.	Drug	Arm C : Sotatercept

Primary outcome

Right Ventricular Stroke Volume (RVSV) flow on each therapy measured by MRI RSVS (flow) on each therapy measured by MRI
Time frame: Baseline to Week 12 of each crossover period
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
Daily Hemodynamic Detection of Treatment Response During Sotatercept Escalation
Time frame: Baseline (Week 0) through Week 24
Within-patient changes in continuous, remote-monitored Total Pulmonary Resistance (TPR), mean Pulmonary Artery Pressure (mPAP), Cardiac Output (CO), Stroke Volume (SV), and Heart Rate (HR) detected by the CardioMEMS sensor following treatment escalation with sotatercept, correlated with end-of-treatment RVSV measured by cardiac MRI.

25 secondary outcomes

Haemodynamics - Total Pulmonary Resistance (TPR)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
Haemodynamics - mean Pulmonary Artery Pressure (mPAP)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
Haemodynamics - Cardiac Output (CO)
Time frame: Part 1 : From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
Haemodynamics - Cardiac Index
Time frame: Part 1 : From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
Haemodynamics - Stroke Volume (SV)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
Haemodynamics - Heart Rate (HR)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
6 Minute Walk Test
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
NTpro-BNP
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks.
MRI - Right Ventricular Ejection Fraction (RVEF)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Right Ventricular End Systolic Volume (RVESV)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Right Ventricular End Diastolic Volume (RVEDV)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Right Ventricular Stroke Volume (RVSV)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Left Ventricular Volume Fraction (LVEF)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Left Ventricular End Systolic Volume (LVESV)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Left Ventricular End Diastolic Volume LVEDV
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Left Ventricular Stroke Volume (LVSV)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
MRI - Left Ventricular Stroke Volume (LVSV) flow
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
Patient Reported Outcomes (PRO) - Quality of Life (QoL) (EmPHasis-10)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
Patient Reported Outcomes (PRO) - Medication Compliance (PHoenix PRO)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks
Patient Reported Outcomes (PRO) - Medication Side Effects
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
Patient Reported Outcomes (PRO) - Depression symptoms (GAD-2/7)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
Patient Reported Outcomes (PRO) - Anxiety symptoms (PHQ-2/9)
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
WHO functional class
Time frame: Part 1: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks Part 2: From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
EuroQoL-5D-5L
Time frame: Part 2 only : From baseline and area under the curve to 3 weeks, 6 weeks, 12 weeks, 18 weeks, and 24 weeks
PHoenix UTAUT questionnaire
Time frame: Part 1 only: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
Background: PubMed 33632769Swift 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.
Individual participant dataSharing planned: No. Research samples will be transferred to the Sheffield Biorepository with no identifiable personal data. Data will be collected and hosted and processed by University of Oxford (data supplier). Authorised data originators include, but are not limited to PIs and delegated staff; Participants; and Core Imaging Laboratory. The trial manager will lead the data verification process. Remote monitoring data will be managed through the Merlin.net system (Device supplier - Abbott). Pseudonymised data will then be transferred, held, analysed and archived securely at the University of Glasgow (processor). Data will also be transferred to the University of Sheffield and Newcastle University (processor) for study analysis. The University of Sheffield shall own all right, title and interest in and to all of the University of Sheffield Data. For the purposes of the Data Protection Legislation, Sheffield Teaching Hospitals (sponsor) is the Data Controller.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Alexander Rothman, MD / PhD principal investigator

University of Sheffield

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Right Ventricular Stroke Volume (RVSV) flow on each therapy measured by MRI RSVS (flow) on each therapy measured by MRI (time frame: Baseline to Week 12 of each crossover period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05825417, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2026.