# The Placebo Effect in Chronic Thromboembolic Pulmonary Hypertension Trials: A Systematic Review and Meta-Analysis

## TL;DR

This study reviews clinical trials for chronic thromboembolic pulmonary hypertension and finds that the placebo effect is small and not statistically significant.

## Contribution

The study provides the first systematic review and meta-analysis of placebo effects specifically in CTEPH clinical trials.

## Key findings

- Placebo arms showed no significant change in 6-minute walk test distance.
- Quality of life and other clinical measures in placebo groups showed minimal and non-significant improvements.
- The placebo effect in CTEPH trials is small and not statistically significant.

## Abstract

Introduction: Placebo-controlled studies are crucial in clinical trials, but the placebo effect can vary across conditions. We aimed to assess the placebo effect in chronic thromboembolic pulmonary hypertension (CTEPH) trials. Methods: We conducted a systematic review and included randomized placebo-controlled trials investigating CTEPH interventions. Primary outcomes were the pre–post changes in the 6 min walk test (6MWT) and quality of life in the placebo arms. Secondary outcomes included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, and NT-proBNP levels. Meta-analyses were performed using random-effects models. Results: Seven trials with 270 CTEPH patients in placebo arms were analyzed. The average 6MWT change was not significant (−1.31 m; 95%CI −12.49 to +9.79). Quality of life with EQ-5D was not significantly improved (−0.04; 95%CI −0.10 to +0.02). mPAP, PVR, cardiac index, and NT-proBNP also demonstrated non-significant changes with small magnitudes. Conclusions: The placebo effect in CTEPH trials was not statistically significant and had small magnitude but should not discourage the use of placebo-controlled trials where applicable and ethical.