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

Trials. 2020 Feb 10;21(1):158. doi: 10.1186/s13063-020-4103-z.

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.

Keywords: Psoriasis, Palmoplantar pustulosis, Randomised controlled trial, Anakinra, Adaptive trial,; Statistical analysis plan.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / adverse effects
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Male
  • Medication Adherence
  • Patient Reported Outcome Measures
  • Psoriasis / drug therapy*
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Interleukin 1 Receptor Antagonist Protein