Top

Published in:

Open Access 01-12-2022 | Idiopathic Pulmonary Fibrosis | Study protocol

PAciFy Cough—a multicentre, double-blind, placebo-controlled, crossover trial of morphine sulphate for the treatment of pulmonary Fibrosis Cough

Authors: Zhe Wu, Winston Banya, Nazia Chaudhuri, Ira Jakupovic, Toby M. Maher, Brijesh Patel, Lisa G. Spencer, Muhunthan Thillai, Alex West, John Westoby, Marlies Wijsenbeek, Jaclyn Smith, Philip L. Molyneaux

Published in: Trials | Issue 1/2022

Abstract

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that leads to lung scarring. Cough is reported by 85% of patients with IPF and can be a distressing symptom with a significant impact on patients’ quality of life. There are no proven effective therapies for IPF-related cough. Whilst morphine is frequently used as a palliative agent for breathlessness in IPF, its effects on cough have never been tested. PAciFy Cough is a multicenter, double-blind, placebo-controlled, crossover trial of morphine sulphate for the treatment of cough in IPF.

Methods

We will recruit 44 subjects with IPF prospectively from three interstitial lung disease units in the UK, namely the Royal Brompton Hospital, Manchester University NHS Foundation Trust (MFT) and Aintree University Hospital NHS Foundation Trust. Patients will be randomised (1:1) to either placebo twice daily or morphine sulphate 5 mg twice daily for 14 days. They will then crossover after a 7-day washout period. The primary endpoint is the percent change in daytime cough frequency (coughs per hour) from baseline as assessed by objective cough monitoring at day 14 of treatment.

Discussion

This multicentre, randomised trial will assess the effect of opioids on cough counts and cough associated quality of life in IPF subjects. If proven to be an effective intervention, it represents a readily available treatment for patients.

Trial registration

The study was approved by the UK Medicines and Healthcare Regulatory Agency (Ref: CTA 21268/0224/001-0001 – EUDRACT 2019-003571-19 – Protocol Number RBH2019/001) on 08 April 2020, in compliance with the European Clinical Trials Directive and the Medicines for Human Use (Clinical Trials) Regulations 2004 and its subsequent amendments. The study was provided with ethical approval by the London Brent Research Ethics Committee (Ref: 20/LO/0368) on 21 May 2020 and is registered with clinicaltrials.gov (NCT04429516) on 12 June 2020, available at https://clinicaltrials.gov/ct2/show/NCT04429516

Available only for authorised users

Maher TM, Wells AU, Laurent GJ. Idiopathic pulmonary fibrosis: Multiple causes and multiple mechanisms? Eur Respir J. 2007;30(5):835–9. https://doi.org/10.1183/09031936.00069307.CrossRefPubMed

British Lung Foundation. Lung disease in the UK - big picture statistics [Internet]. [cited 2019 Aug 4]. Available from: https://statistics.blf.org.uk/lung-disease-uk-big-picture

Navaratnam V, Fleming KM, West J, CJP S, Jenkins RG, Fogarty A, et al. The rising incidence of idiopathic pulmonary fibrosis in the UK. Thorax. 2011;66(6):462–7.CrossRef

Rajala K, Lehto JT, Sutinen E, Kautiainen H, Myllärniemi M, Saarto T. mMRC dyspnoea scale indicates impaired quality of life and increased pain in patients with idiopathic pulmonary fibrosis. ERJ Open Res. 2017;3(4):00084–2017.CrossRef

Ryerson CJ, Abbritti M, Ley B, Elicker BM, Jones KD, Collard HR. Cough predicts prognosis in idiopathic pulmonary fibrosis. Respirology. 2011;16(6):969–75. https://doi.org/10.1111/j.1440-1843.2011.01996.x.CrossRefPubMed

Turner-Warwick M, Burrows B, Johnson A. Cryptogenic fibrosing alveolitis: clinical features and their influence on survival. Thorax. 1980;35(3):171–80. https://doi.org/10.1136/thx.35.3.171.CrossRefPubMedPubMedCentral

Gries KS, Esser D, Wiklund I. Content validity of CASA-Q cough domains and UCSD-SOBQ for use in patients with idiopathic pulmonary fibrosis. Glob J Health Sci. 2013;5(6):131–41. https://doi.org/10.5539/gjhs.v5n6p131.CrossRefPubMedPubMedCentral

Yount SE, Beaumont JL, Chen SY, Kaiser K, Wortman K, Van Brunt DL, et al. Health-related quality of life in patients with idiopathic pulmonary fibrosis. Lung. 2016;194(2):227–34. https://doi.org/10.1007/s00408-016-9850-y.CrossRefPubMed

Hope-Gill BDM, Hilldrup S, Davies C, Newton RP, Harrison NK. A study of the cough reflex in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003;168(8):995–1002.CrossRef

10.

Scholand MB, Wolff R, Crossno PF, Sundar K, Winegar M, Whipple S, et al. Severity of cough in idiopathic pulmonary fibrosis is associated with MUC5 B genotype. Cough. 2014;10(1):3. https://doi.org/10.1186/1745-9974-10-3.CrossRefPubMedPubMedCentral

11.

Horton MR, Danoff SK, Lechtzin N. Thalidomide inhibits the intractable cough of idiopathic pulmonary fibrosis. Thorax. 2008;63(8):749. https://doi.org/10.1136/thx.2008.098699.CrossRefPubMed

12.

Van Manen MJG, Birring SS, Vancheri C, Cottin V, Renzoni EA, Russell AM, et al. Cough in idiopathic pulmonary fibrosis. Eur Respir Rev [Internet]. 2016;25(141):278–86. Available from:. https://doi.org/10.1183/16000617.0090-2015.CrossRefPubMed

13.

Birring SS, Wijsenbeek MS, Agrawal S, van den Berg JWK, Stone H, Maher TM, et al. A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial. Lancet Respir Med. 2017;5(10):806–15. https://doi.org/10.1016/S2213-2600(17)30310-7.CrossRefPubMed

14.

Morice AH, Menon MS, Mulrennan SA, Everett CF, Wright C, Jackson J, et al. Opiate therapy in chronic cough. Am J Respir Crit Care Med. 2007;175(4):312–5. https://doi.org/10.1164/rccm.200607-892OC.CrossRefPubMed

15.

Kohberg C, Andersen CU, Bendstrup E. Opioids: an unexplored option for treatment of dyspnea in IPF. Eur Clin Respir J [Internet]. 2016;3(1). Available from: https://doi.org/10.3402/ecrj.v3.30629

16.

Bajwah S, Davies JM, Tanash H, Currow DC, Oluyase AO, Ekström M. Safety of benzodiazepines and opioids in interstitial lung disease: a national prospective study. Eur Respir J [Internet]. 2018;52(6). Available from: https://doi.org/10.1183/13993003.01278-2018

17.

Smith JA, Holt K, Dockry R, Sen S, Sheppard K, Turner P, et al. Performance of a digital signal processing algorithm for the accurate quantification of cough frequency. Eur Respir J [Internet]. 2021;2004271. Available from: https://doi.org/10.1183/13993003.04271-2020

18.

Nolan CM, Birring SS, Maddocks M, Maher TM, Patel S, Barker RE, et al. King’s Brief Interstitial Lung Disease questionnaire: responsiveness and minimum clinically important difference. Eur Respir J. 2019;54(3):1900281. https://doi.org/10.1183/13993003.00281-2019.CrossRefPubMed

Title: PAciFy Cough—a multicentre, double-blind, placebo-controlled, crossover trial of morphine sulphate for the treatment of pulmonary Fibrosis Cough
Authors: Zhe Wu
Winston Banya
Nazia Chaudhuri
Ira Jakupovic
Toby M. Maher
Brijesh Patel
Lisa G. Spencer
Muhunthan Thillai
Alex West
John Westoby
Marlies Wijsenbeek
Jaclyn Smith
Philip L. Molyneaux
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Idiopathic Pulmonary Fibrosis
Cough
Cough
Morphine
Cough
Published in: Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-022-06068-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

PAciFy Cough—a multicentre, double-blind, placebo-controlled, crossover trial of morphine sulphate for the treatment of pulmonary Fibrosis Cough

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2022

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial

Effectiveness of a training intervention to improve the management of vertigo in primary care: a multicentre cluster-randomised trial, VERTAP

Cardiac magnetic resonance imaging versus computed tomography to guide transcatheter aortic valve replacement: study protocol for a randomized trial (TAVR-CMR)

Resources for Enhancing Alzheimer’s Caregiver Health in Vietnam (REACH VN): study protocol for a cluster randomized controlled trial to test the efficacy of a family dementia caregiver intervention in Vietnam

Effectiveness of promotion and support for physical activity maintenance post total hip arthroplasty—study protocol for a pragmatic, assessor-blinded, randomized controlled trial (the PANORAMA trial)

Study protocol for the Multimodal Approach to Preventing Suicide in Schools (MAPSS) project: a regionally based randomised trial of an integrated response to suicide risk among secondary school students