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

肺动脉高压(PAH)是一种由肺小血管重构和收缩引起的破坏性疾病。批准的治疗方法通过靶向三种不同的生物途径来减少收缩。治疗方法会因副作用和/或疾病恶化而改变。然而，由于需要进行侵入性的、以医院为基础的调查，以评估疾病的严重性并证明治疗的好处，因此无法将患者与有效治疗其疾病的药物相匹配。通过MRC对概念的信心资助的可行性研究，我们开发了使用监管批准的微创监测器进行关键测量的能力，以便在患者在家时评估疾病严重程度和治疗效果。数据每天通过监管部门批准的临床使用的在线门户网站传递给护理团队，使早期、远程评估个别患者的治疗益处成为可能。在肺动脉高压(PAH)患者中，这项研究将评估植入性/远程技术早期评估临床疗效的能力，并将患者与对他们有效的药物配对。40名根据指南推荐治疗建立的PAH患者将被植入经批准的医疗设备并建立远程监测。在口服前列环素IP受体激动剂和可溶性鸟苷环化酶刺激剂的随机交叉研究中，将监测生理、活动和生活质量。这项研究将以一种以前无法实现的方式评估治疗强化和降级的生理学。如果成功，该技术方法将促进该领域的新研究设计，提供一个有潜力改变实验医学、治疗开发和为肺动脉高压患者提供个性化药物的平台。

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.