MICA: Pulmonary Hypertension: intensification and personalisation of combination Rx (PHoenix)

Pulmonary arterial hypertension (PAH) is a devastating disease driven by remodelling and constriction of the small blood vessels of the lungs. Approved therapies reduce constriction by targeting three distinct biological pathways. Therapies are changed due to side effects and/or disease worsening. However, due to the invasive, hospital-based investigations required to assess disease severity and demonstrate benefit of treatment, there is no way to match patients to drugs effective for their disease. Through an MRC Confidence-in-Concepts funded feasibility study we have developed the capacity to use regulatory approved, minimally-invasive monitors to make key measurements that allow assessment of disease severity and treatment effect while patients are at home. Data is relayed daily to care teams through regulatory approved, clinically used online portals, making early, remote evaluation of treatment benefit in an individual patient possible.

In patients with pulmonary arterial hypertension (PAH) this study will: evaluate the capacity of implantable/remote technology for early evaluation of clinical efficacy and matching patients to drugs that work for them.

Forty patients with PAH established on guideline recommended therapy will be implanted with approved medical devices and remote monitoring established. Physiology, activity and quality-of-life will be monitored during a randomised cross-over study of oral prostacyclin IP receptor agonist and soluble guanylate cyclase stimulator.

The study will assess the physiology of therapeutic intensification and de-escalation in a manner previously unachievable. If successful, the technological approach will facilitate novel study designs in the area, providing a platform that has the potential to transform experimental medicine, therapeutic development and personalised medicine for patients with pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a devastating disease driven by remodelling and constriction of the small blood vessels of the lungs. Approved therapies reduce constriction by targeting three distinct biological pathways. Therapies are changed due to side effects and/or disease worsening. However, due to the invasive/hospital-based investigations required to assess disease severity and demonstrate benefit of treatment, there is no way to match patients to drugs effective for their disease. Through an MRC Confidence-in-Concept funded feasibility study we have developed the capacity to use regulatory-approved, minimally-invasive monitors to make key measurements that allow assessment of disease severity and treatment effect while patients are at home. Data are relayed daily to care teams through regulatory-approved, clinically-used online portals making early, remote evaluation of treatment benefit and disease severity possible.

This study aims to establish a means for early evaluation of clinical efficacy and personalised medicine in patients with PAH.

Forty patients with PAH established on phosphodiesterase-5 inhibitor and endothelin receptor antagonist will be implanted with regulatory-approved medical devices and remote monitoring established. Physiology, activity and quality-of-life will be monitored during a randomised cross-over study of oral prostacyclin IP receptor agonist and soluble guanylate cyclase stimulator and ability to detect change compared to established and emerging clinical endpoints including: MRI measures of right ventricular function, haemodynamics, NTpro-BNP and six-minute walk distance.

If successful, the study will assess pathophysiology in a manner not previously possible. This will provide a platform that has the potential to transform experimental medicine, therapeutic development and personalised medicine for patients with pulmonary hypertension.