Lead Investigator: Howard Smith, Sheffield Teaching Hospitals
Title of Proposal Research: An individual patient data meta-analysis of clinical endpoints in pulmonary hypertension with interstitial lung disease (PH-ILD)
Vivli Data Request: 8058
Funding Source: None
Potential Conflicts of Interest: Dr. Laura Price receives educational support from Janssen, MSD and Ferrer. Dr. Robin Condliffe reports “Honoraria for Speakers Fees and Advisory Boards from Janssen and MSD.
Summary of the Proposed Research:
Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD). Interstitial lung disease is an umbrella term used for a large group of diseases that cause scarring (fibrosis) of the lungs, frequently associated with poor prognosis. Pulmonary Hypertension can be defined as a mean Pulmonary Artery Pressure (mPAP) of over 20 millimetres of mercury (mmHg – the unit measure of blood pressure). The pulmonary artery is the major blood vessel supplying deoxygenated blood to the lungs from the right side of the heart. The increased pressure in the PA are a result of vascular remodelling (alterations in the structure of vessels) in the pulmonary artery and lead to remodelling of the right side of the heart. This results in breathlessness, reduced exercise tolerance, collection of fluid within the lungs and an increased risk of death.
PH in association with interstitial lung disease (PH-ILD) is often treated with pulmonary vasodilators although few data exist to support this practice. Vasodilators are medications which cause a decrease in pressure in blood vessels. If a blood vessel with abnormally high pressure such as the pulmonary artery in PH is treated with a vasodilator, symptoms can improve and the life span of the patient may be increased.
Incidence is defined as the number of new diagnoses per a specified unit of time. A 2021 study looked at the incidence of ILD in Europe and the UK and found the median incidence of ILD per year was 7.22 per 100 000 population for men and 4.34 per 100 000 population for women, as much as 16% of patients at presentation have a diagnosis of pulmonary hypertension.
In order to design effective clinical trials to test pharmacological interventions in those with PH-ILD, it is essential that randomised controlled trials (RCT) are looking for real effects between an intervention and outcome with feasible recruitment strategies. Determining the specific benefits of vasodilator intervention upon individuals with PH-ILD in published trials will offer an endpoint for appropriate choice of endpoints in RCT design.
How the research will be conducted?
Studies will be screened independently by two authors. Individual participant data will be requested and analysed for overall effect of the study intervention and later included in a meta-analysis.
What design and methods you have you chosen and why?
We will take a two-stage approach to individual participant data meta-analysis that allows us to derive effect sizes from independent studies and model consistently across all datasets.
The effects will then be included in a meta-analysis, maintaining the independence of each individual study.
INSTAGE: A 24-week, Double-blind, Randomized, Parallel-group Study Evaluating the Efficacy and Safety of Oral Nintedanib Co-administered With Oral Sildenafil, Compared to Treatment With Nintedanib Alone, in Patients With Idiopathic Pulmonary Fibrosis (IPF) and Advanced Lung Function Impairment
Data Contributor: Boehringer Ingelheim
Study ID: NCT02802345
Sponsor ID: 1199.36
A Double-blind, Randomized, Placebo-controlled, Multicenter, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Macitentan in Patients With Idiopathic Pulmonary Fibrosis
Data Contributor: Johnson & Johnson
Study ID: NCT00903331
Sponsor ID: AC-055B201
Effects of Bosentan on Morbidity and Mortality in Patients With Idiopathic Pulmonary Fibrosis – a Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Event-driven, Group Sequential, Phase III Study.
Data Contributor: Johnson & Johnson
Study ID: NCT00391443
Sponsor ID: AC-052-321