Antitussive effect of carcainium chloride in patients with chronic cough and idiopathic interstitial pneumonias: A pilot study.

Abstract

BACKGROUND:

Cough is a common presenting symptom in patients with idiopathic interstitial pneumonia (IIP); it is often disabling, and lacks effective treatment. Studies in animals suggest that carcainium chloride, a quaternary derivative of the local anesthetic lidocaine, is able to inhibit experimentally induced cough by a mechanism of action distinct from that of lidocaine.

OBJECTIVE:

To determine the effectiveness of aerosolised carcainium chloride (VRP700) in controlling cough in patients with IIP.

METHODS:

Eight female patients (mean age 71 years) with IIP were investigated in a double blind, randomised, placebo controlled crossover, adaptive contingency study design (EudraCT Number 2010-021350-19). The study consisted of a screening visit to assess the eligibility of patients, and two separated (48-72 h) study days. On the two study days, patients were randomised to receive either nebulized VRP700 (1.0 mg/kg) on the first study visit followed by nebulised placebo (sodium chloride 0.9%) on the second visit, or placebo on the first visit followed by VRP700 on the second visit. The primary endpoint was cough frequency over a 4-h assessment period; secondary endpoints were subjective cough-related level of discomfort as assessed by a visual analogue scale (VAS) and the subjective response to treatment as assessed by a quality of life question. Safety (ECG, spirometry, urine and blood tests) and adverse events occurring during the trial were also investigated.

RESULTS:

In all patients both VRP700 and placebo decreased cough frequency; however, mean decreases in cough frequency after treatment with VRP700 were significantly (P < 0.001) higher than with placebo. Similarly, mean reductions in VAS score were significantly (P < 0.001) higher after treatment with VRP 700 compared with placebo. All but one patient indicated that they felt better after receiving VRP700. No adverse events were reported during the study, nor were any changes in ECG variables, spirometry, urine and blood tests noted.

CONCLUSION:

The results of this exploratory study indicate that nebulised VRP700 improved cough and quality of life in hospitalised IIP patients with no significant side effects. A larger trial is warranted to assess these promising results.

• Authors: Federico Lavorini, Domenico Spina, Michael J Walker, Lui Franciosi, Clive P Page, Giovanni A Fontana
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 40 Pg. 91-4 (10 2016) ISSN: 1522-9629 [Electronic] England
• PMID: 27538683 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Aerosols
• Anesthetics, Local
• Antitussive Agents
• Lidocaine
• carcainium chloride

Topics

• Administration, Inhalation
• Aerosols
• Aged
• Anesthetics, Local (administration & dosage, adverse effects, therapeutic use)
• Antitussive Agents (administration & dosage, adverse effects, therapeutic use)
• Chronic Disease
• Cough (drug therapy, etiology)
• Cross-Over Studies
• Double-Blind Method
• Female
• Humans
• Idiopathic Interstitial Pneumonias (drug therapy, physiopathology)
• Lidocaine (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Male
• Middle Aged
• Pilot Projects
• Quality of Life