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Active, not recruiting

NCT Number: NCT05825417

Pulmonary Hypertension: Intensification and Personalisation of Combination Rx

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.

Active, not recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Pulmonary Arterial Hypertension Hypertension, Pulmonary Lung Diseases Respiratory Tract Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Sheffield Teaching Hospitals NHS FT

Sheffield, S10 2JF, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Part 1:

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

Part 2:

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 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

Exclusion criteria

  • 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

Treatment and study plan

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.

Other names: Uptravi, oral prostacyclin IP receptor agonist (OPA)

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.

Other names: Adempas, soluble guanylate cyclase stimulator (sGCS)

CardioMEMS pulmonary artery pressure monitor

Device

Implantation and remote monitoring established with patient initiated daily readings

Confirm Rx

Device

Implantation and remote monitoring established with automated daily readings / downloads

Sotatercept

Drug

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.

Primary outcomes

  1. 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

  2. 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.

Secondary outcomes

  1. 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.

    Change in TPR (Woods Units) on each therapy to determine clinical efficacy

  2. 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.

    Change in mPAP (mmHg) on each therapy to determine clinical efficacy

  3. 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.

    Change in CO (L/min) on each therapy to determine clinical efficacy

  4. 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

    Change in cardiac index (L/min/m^2) on each therapy to determine clinical efficacy

  5. 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.

    Change in SV (mL) on each therapy to determine clinical efficacy

  6. 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.

    Change in HR (bpm) on each therapy to determine clinical efficacy

  7. 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.

    Change on each therapy to determine clinical efficacy

  8. 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.

    Change on each therapy to determine clinical efficacy

  9. 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

    RVEF (%) on each therapy to determine clinical efficacy

  10. 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

    RVESV (mL/m^2) on each therapy to determine clinical efficacy

  11. 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

    RVEDV (mL/m^2) on each therapy to determine clinical efficacy

  12. 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

    RVSV (mL) on each therapy to determine clinical efficacy

  13. 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

    LVEF (%) on each therapy to determine clinical efficacy

  14. 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

    LVESV (mL/m^2) on each therapy to determine clinical efficacy

  15. 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

    LVEDV (mL/m^2) on each therapy to determine clinical efficacy

  16. 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

    LVSV (mL) on each therapy to determine clinical efficacy

  17. 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

    LVSV flow on each therapy to determine clinical efficacy

  18. 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

    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)

  19. 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

    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)

  20. 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

    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)

  21. 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

    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)

  22. 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

    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)

  23. 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

    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.

  24. 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

    The EuroQoL-5D-5L is included for future health economic evaluation of sotatercept. (free for non-commercial use

  25. PHoenix UTAUT questionnaire

    Time frame: Part 1 only: From baseline and area under the curve to 4 weeks, 8 weeks and 12 weeks

    Evaluation of remote monitoring technology and devices.

Sponsors and collaborators

Lead sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Other

Collaborators

  • University of Cambridge
  • University of Glasgow
  • University of Newcastle Upon-Tyne
  • University of Sheffield

Registry information

Official study 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)

Acronym: PHoenix

Important dates

Study start
2023
Primary completion
2028
Study completion
2028
First posted
Apr 24, 2023
Registry last updated
Aug 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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