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Bronchodilator's Effects on Exertional Dyspnoea in Pulmonary Arterial Hypertension

NCT02782052 · Status: WITHDRAWN · Phase: PHASE3 · Type: INTERVENTIONAL

Last updated 2020-01-29

No results posted yet for this study

Summary

Activity-related dyspnoea appears to be the earliest and the most frequent complaint for which patients with PAH seek medical attention. This symptom progresses relentlessly with time leading invariably to avoidance of activity with consequent skeletal muscle deconditioning and an impoverished quality of life. Unfortunately, effective management of this disabling symptom awaits a better understanding of its underlying physiology. Our team has recently showed that PAH patients may exhibit reduced expiratory flows at low lung volumes at spirometry (namely instantaneous forced expiratory flows measured after 50% and 75% of the FVC has been exhaled \[FEF50% and FEF75%\] lower than predicted), despite a preserved forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) . Several studies have shown that such a finding ("small airway disease") could be common in certain PAH cohorts, have either related it to incidental descriptions of airway wall thickening with lymphocytic infiltration in PAH or proposed several other speculative explanatory mechanisms, either biological or mechanical. Whatever its cause, reduced expiratory flows at low lung volumes imply that the operating tidal volume (VT) range becomes closer than normally to residual volume (RV) mostly through an increase in RV (elevated residual volume/total lung capacity ratio, RV/TLC). The reduced difference between forced and tidal expiratory flows promotes dynamic lung hyperinflation \[i.e., a progressive increase in end-expiratory lung volume (EELV)\] under conditions of increased ventilatory demand. Dynamic lung hyperinflation (DH) is well known to have serious sensory consequences, i.e., increase in dyspnoea intensity, as clearly shown in patients with chronic obstructive pulmonary disease and chronic heart failure. The aim of this study is to evaluate whether administration of inhaled BDs (β2-agonist and/or anticholinergic), as add-ons to vasodilators, would be beneficial to PAH patients by reducing and/or delaying the rate of onset of DH, thus ameliorating the exertional symptoms in patients with stable PAH undergoing high-intensity constant work-rate (CWR) cycle endurance test.

This is a randomised double-blind placebo-controlled crossover study. Design: 5 visits; V1: screening, familiarization, incremental cardiopulmonary exercise testing (CPET); V2: constant work-rate (CWR-CPET); V3, V4 and V5: CWR-CPET after intervention, in a random order: Placebo (P), Ipratropium Bromide (IB), Ipratropium Bromide + Salbutamol (IB+SALB).

Conditions

Interventions

DRUG

Nebulized ipratropium bromide

Administration at V3 or V4 or V5 in a random order: * Placebo (P; sterile 0.9% sodium chloride solution) * Or nebulized ipratropium bromide (IB; 0.5mg/2mL) alone * Or nebulized combination ipratropium bromide with salbutamol (IB+SALB; 0.5mg/2mL + 2.5mg/2.5mL).

DRUG

Nebulized combination ipratropium bromide with salbutamol

Administration at V3 or V4 or V5 in a random order: * Placebo (P; sterile 0.9% sodium chloride solution) * Or nebulized ipratropium bromide (IB; 0.5mg/2mL) alone * Or nebulized combination ipratropium bromide with salbutamol (IB+SALB; 0.5mg/2mL + 2.5mg/2.5mL).

DRUG

Nebulized Placebo

Administration at V3 or V4 or V5 in a random order: * Placebo (P; sterile 0.9% sodium chloride solution) * Or nebulized ipratropium bromide (IB; 0.5mg/2mL) alone * Or nebulized combination ipratropium bromide with salbutamol (IB+SALB; 0.5mg/2mL + 2.5mg/2.5mL).

Sponsors & Collaborators

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Model
CROSSOVER

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2016-07-31
Primary Completion
2018-10-31
Completion
2019-02-28

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02782052 on ClinicalTrials.gov