New perspectives in long-term outcomes in clinical trials of pulmonary arterial hypertension

Eur Respir Rev. 2013 Dec;22(130):495-502. doi: 10.1183/09059180.00006413.

Abstract

The past two decades have seen significant improvements in the management of patients with pulmonary arterial hypertension (PAH). Although outcome has improved, long-term prognosis remains unsatisfactory. The development of new treatment options is clearly important. Equally important is testing new agents in trials designed to provide robust evidence for sustained clinical benefits enabling clinicians to determine the optimal treatment strategy for individual patients. End-points such as the change in 6-min walk distance (6MWD) have been pivotal in the registration trials of currently available PAH-specific therapies. However, as current clinical trials enrol patients with milder disease, many already on background therapy, there is growing evidence that change from baseline in 6MWD is a weak surrogate of outcome in PAH. In addition, while short-term trials allowed for the rapid approval of PAH therapies in the past, there is increasing recognition that clinical trials for new agents must provide evidence of long-term benefits. Clinical trials need to evolve to provide the long-term, clinically relevant data required to appropriately assess new therapies. Event-driven long-term morbidity and mortality trials are currently underway, and will provide robust data on the frequency and timing of events, and are likely to reflect the future of clinical trial design in PAH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Clinical Trials as Topic / methods*
  • Disease Progression
  • Endpoint Determination
  • Exercise Test*
  • Exercise Tolerance / drug effects
  • Familial Primary Pulmonary Hypertension
  • Hemodynamics / drug effects
  • Humans
  • Hypertension, Pulmonary / diagnosis*
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / mortality
  • Hypertension, Pulmonary / physiopathology
  • Predictive Value of Tests
  • Research Design*
  • Time Factors
  • Treatment Outcome
  • Walking

Substances

  • Antihypertensive Agents