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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

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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

Location status: Recruiting

Location contact

Alex Rothman

CONTACT

About this study

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.

Who can participate

Healthy volunteers accepted: No

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

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

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

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

    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

Secondary outcomes

  1. Haemodynamics - Total Pulmonary Resistance (TPR)

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

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

  2. Haemodynamics - mean Pulmonary Artery Pressure (mPAP)

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

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

  3. Haemodynamics - Cardiac Output (CO)

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

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

  4. Haemodynamics - Cardiac Index

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

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

  5. Haemodynamics - Stroke Volume (SV)

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

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

  6. Haemodynamics - Heart Rate (HR)

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

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

  7. 6 Minute Walk Test

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

    Change on each therapy to determine clinical efficacy

  8. NTpro-BNP

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

    Change on each therapy to determine clinical efficacy

  9. MRI - Right Ventricular Ejection Fraction (RVEF)

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

    RVEF (%) on each therapy to determine clinical efficacy

  10. MRI - Right Ventricular End Systolic Volume (RVESV)

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

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

  11. MRI - Right Ventricular End Diastolic Volume (RVEDV)

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

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

  12. MRI - Right Ventricular Stroke Volume (RVSV)

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

    RVSV (mL) on each therapy to determine clinical efficacy

  13. MRI - Left Ventricular Volume Fraction (LVEF)

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

    LVEF (%) on each therapy to determine clinical efficacy

  14. MRI - Left Ventricular End Systolic Volume (LVESV)

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

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

  15. MRI - Left Ventricular End Diastolic Volume LVEDV

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

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

  16. MRI - Left Ventricular Stroke Volume (LVSV)

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

    LVSV (mL) on each therapy to determine clinical efficacy

  17. MRI - Left Ventricular Stroke Volume (LVSV) flow

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

    LVSV flow on each therapy to determine clinical efficacy

  18. Patient Reported Outcomes (PRO) - Quality of Life (QoL) (EmPHasis-10)

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

Study contacts

Contact information is provided by the study sponsor or research team.

Shravya Rao

CONTACT

[email protected]

+44 (0) 114 2159550

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
2027
Study completion
2027
First posted
Apr 24, 2023
Registry last updated
Jun 5, 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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