Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2020

Open Access 01-12-2020 | Anakinra | Update

A randomised placebo controlled trial of anakinra for treating pustular psoriasis: statistical analysis plan for stage two of the APRICOT trial

Authors: Suzie Cro, Prakash Patel, Jonathan Barker, David A. Burden, Christopher E. M. Griffiths, Helen J. Lachmann, Nick J. Reynolds, Richard B. Warren, Francesca Capon, Catherine Smith, Victoria Cornelius

Published in: Trials | Issue 1/2020

Login to get access

Abstract

Background

Current treatment options for Palmoplantar Pustulosis (PPP), a debilitating chronic skin disease which affects the hands and feet, are limited. The Anakinra for Pustular psoriasis: Response in a Controlled Trial (APRICOT) aims to determine the efficacy of anakinra in the treatment of PPP. This article describes the statistical analysis plan for the final analysis of this two-staged trial, which was determined prior to unblinding and database lock. This is an update to the published protocol and stage one analysis plan.

Methods

APRICOT is a randomised, double-blind, placebo-controlled trial of anakinra versus placebo, with two stages and an adaptive element. Stage one compared treatment arms to ensure proof-of-concept and determined the primary outcome for stage two of the trial. The primary outcome was selected to be the change in Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Secondary outcomes include other investigator-assessed efficacy measures of disease severity, participant-reported measures of efficacy and safety measures. This manuscript describes in detail the outcomes, sample size, general analysis principles, the pre-specified statistical analysis plan for each of the outcomes, the handling of missing outcome data and the planned sensitivity and supplementary analyses for the second stage of the APRICOT trial.

Discussion

This statistical analysis plan was developed in compliance with international trial guidelines and is published to increase transparency of the trial analysis. The results of the trial analysis will indicate whether anakinra has a role in the treatment of PPP.

Trial registration

ISCRTN, ISCRTN13127147. Registered on 1 August 2016. EudraCT Number 2015-003600-23. Registered on 1 April 2016.
Appendix
Available only for authorised users
Literature
1.
Marsland AM, Chalmers RJ, Hollis S, Leonardi-Bee J, Griffiths CE. Interventions for chronic palmoplantar pustulosis. Cochrane Database Syst Rev. 2006;25(1):Cd001433.
2.
Li M, Han J, Lu Z, Li H, Zhu K, Cheng R, et al. Prevalent and rare mutations in IL-36RN gene in Chinese patients with generalized pustular psoriasis and psoriasis vulgaris. J Invest Dermatol. 2013;133(11):2637–9.CrossRef
3.
Onoufriadis A, Simpson MA, Pink AE, Di Meglio P, Smith CH, Pullabhatla V, et al. Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet. 2011;89(3):432–7.CrossRef
4.
Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY, Fraitag S, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365(7):620–8.CrossRef
5.
Cornelius V, Wilson R, Cro S, Barker J, Burden D, Griffiths CEM, et al. A small population, randomised, placebo-controlled trial to determine the efficacy of anakinra in the treatment of pustular psoriasis: study protocol for the APRICOT trial. Trials. 2018;19(1):465.CrossRef
6.
Cro S, Smith C, Wilson R, Cornelius V. Treatment of pustular psoriasis with anakinra: a statistical analysis plan for stage 1 of an adaptive two-staged randomised placebo-controlled trial. Trials. 2018;19(1):534.CrossRef
7.
Lassus A, Geiger JM. Acitretin and etretinate in the treatment of palmoplantar pustulosis: a double-blind comparative trial. Br J Dermatol. 1988;119(6):755–9.CrossRef
8.
Kahan BC, Morris TP. Reporting and analysis of trials using stratified randomisation in leading medical journals: review and reanalysis. BMJ. 2012;345:e5840.CrossRef
9.
Kahan BC, Morris TP. Analysis of multicentre trials with continuous outcomes: When and how should we account for centre effects? Stat Med. 2013;32(7):1136–49.CrossRef
10.
Senn SJ. Covariate imbalance and random allocation in clinical trials. Stat Med. 1989;8(4):467–75.CrossRef
11.
Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet. 2001;357(9263):1191–4.CrossRef
12.
European Medicines Agency. Guideline on adjustment for baseline covariates in clinical trials. London: 2015. EMA/CHMP/295050/2013.
13.
Pickering RM, Weatherall M. The analysis of continuous outcomes in multi-centre trials with small centre sizes. Stat Med. 2007;26(30):5445–56.CrossRef
14.
Carpenter J, Kenward MG. Missing data in randomised controlled trials - a practical guide. Birmingham: National Institute for Health Research; 2007.
15.
White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance for practice. Stat Med. 2011;30(4):377–99.CrossRef
16.
Hardt J, Herke M, Leonhart R. Auxiliary variables in multiple imputation in regression with missing X: a warning against including too many in small sample research. BMC Med Res Methodol. 2012;12(1):184.CrossRef
17.
Rabe-hesketh S, Skrondal A. Multilevel and longitudinal modeling using stata. Third ed. College Station: Stata Press; 2012.
18.
Zink RC, Wolfinger RD, Mann G. Summarizing the incidence of adverse events using volcano plots and time intervals. Clin Trials. 2013;10(3):398–406.CrossRef
19.
White IR, Thompson SG. Adjusting for partially missing baseline measurements in randomized trials. Stat Med. 2005;24(7):993–1007.CrossRef
20.
Sullivan TR, White IR, Salter AB, Ryan P, Lee KJ. Should multiple imputation be the method of choice for handling missing data in randomized trials? Stat Methods Med Res. 2018;27(9):2610–26.CrossRef
21.
Gamble C, Krishan A, Stocken D, lewis s, Juszczak e, Doré c, et al. Guidelines for the content of statistical analysis plans in clinical trials. JAMA. 2017;318(23):2337–43.CrossRef
Metadata
Title
A randomised placebo controlled trial of anakinra for treating pustular psoriasis: statistical analysis plan for stage two of the APRICOT trial
Authors
Suzie Cro
Prakash Patel
Jonathan Barker
David A. Burden
Christopher E. M. Griffiths
Helen J. Lachmann
Nick J. Reynolds
Richard B. Warren
Francesca Capon
Catherine Smith
Victoria Cornelius
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Trials / Issue 1/2020
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-020-4103-z

Other articles of this Issue 1/2020

Trials 1/2020 Go to the issue

Research

Access to routinely collected health data for clinical trials – review of successful data requests to UK registries

Letter

Efficacy and safety of aerosolized intra-tracheal dornase alfa administration in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS): a structured summary of a study protocol for a randomised controlled trial

Study protocol

Brief motivational therapy versus enhanced usual care for alcohol use disorders in primary care in Chile: study protocol for an exploratory randomized trial

Study protocol

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Study protocol

Effect of acupuncture and its influence on cerebral activity in patients with persistent asthma: study protocol for a randomized controlled clinical trial

Study protocol

Stepped-wedge cluster randomised trial of a smoking cessation counselling training programme for midwives treating women with functional health illiteracy and low socioeconomic status (PROMISE): a study protocol