A randomised placebo controlled trial of anakinra for treating pustular psoriasis: statistical analysis plan for stage two of the APRICOT trial
File(s)
Published version
Author(s)
Type
Journal Article
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.
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.
Date Acceptance
2020-01-21
Citation
Trials, 21
ISSN
1745-6215
Publisher
BioMed Central
Journal / Book Title
Trials
Volume
21
Copyright Statement
© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
License URL
Sponsor
National Institute for Health Research
Grant Number
EME Ref: 13/50/17
Subjects
Psoriasis, Palmoplantar pustulosis, Randomised controlled trial, Anakinra, Adaptive trial,
Statistical analysis plan
General & Internal Medicine
1102 Cardiorespiratory Medicine and Haematology
1103 Clinical Sciences
Cardiovascular System & Hematology
Publication Status
Published
Article Number
ARTN 158
Date Publish Online
2020-02-10