一项随机安慰剂对照试验，评估阿那白滞素治疗脓疱型银屑病：APRICOT 试验第二阶段的统计分析计划。

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

机构信息

Imperial Clinical Trials Unit, Imperial College London, W12 7RH, London, UK.

St. John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

出版信息

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

DOI:10.1186/s13063-020-4103-z

PMID:32041649

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7011285/

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.

摘要

背景

掌跖脓疱病（PPP）是一种使人虚弱的慢性皮肤病，影响手和脚，目前的治疗选择有限。Anakinra 治疗脓疱性银屑病：对照试验中的反应（APRICOT）旨在确定 anakinra 治疗 PPP 的疗效。本文描述了这项两阶段试验最终分析的统计分析计划，该计划是在揭盲和数据库锁定之前确定的。这是对已发表方案和第一阶段分析计划的更新。

方法

APRICOT 是一项 anakinra 与安慰剂的随机、双盲、对照试验，具有两阶段和适应性元素。第一阶段比较治疗臂以确保概念验证，并确定试验第二阶段的主要结果。主要结果选择为 8 周时掌跖脓疱病银屑病面积和严重程度指数（PPPASI）的变化。次要结果包括其他研究者评估的疾病严重程度的疗效测量、参与者报告的疗效测量和安全性测量。本文详细描述了结果、样本量、一般分析原则、每个结果的预设统计分析计划、缺失结果数据的处理以及 APRICOT 试验第二阶段的计划敏感性和补充分析。