Measuring skin necrosis in a randomised controlled feasibility trial of heat preconditioning on wound healing after reconstructive breast surgery: study protocol and statistical analysis plan for the PREHEAT trial

Abstract

BackgroundEssential strategies are needed to help reduce the number of post-operative complications and associated costs for breast cancer patients undergoing reconstructive breast surgery. Evidence suggests that local heat preconditioning could help improve the provision of this procedure by reducing skin necrosis. Before testing the effectiveness of heat preconditioning in a definitive randomised controlled trial (RCT), we must first establish the best way to measure skin necrosis and estimate the event rate using this definition.MethodsPREHEAT is a single-blind randomised controlled feasibility trial comparing local heat preconditioning, using a hot water bottle, against standard care on skin necrosis among breast cancer patients undergoing reconstructive breast surgery. The primary objective of this study is to determine the best way to measure skin necrosis and to estimate the event rate using this definition in each trial arm. Secondary feasibility objectives include estimating recruitment and 30 day follow-up retention rates, levels of compliance with the heating protocol, length of stay in hospital and the rates of surgical versus conservative management of skin necrosis. The information from these objectives will inform the design of a larger definitive effectiveness and cost-effectiveness RCT.DiscussionThis article describes the PREHEAT trial protocol and detailed statistical analysis plan, which includes the pre-specified criteria and process for establishing the best way to measure necrosis. This study will provide the evidence needed to establish the best way to measure skin necrosis, to use as the primary outcome in a future RCT to definitively test the effectiveness of local heat preconditioning. The pre-specified statistical analysis plan, developed prior to unblinded data extraction, sets out the analysis strategy and a comparative framework to support a committee evaluation of skin necrosis measurements. It will increase the transparency of the data analysis for the PREHEAT trial.Trial registrationISRCTN ISRCTN15744669. Registered 25 February 2015Electronic supplementary materialThe online version of this article (10.1186/s40814-017-0223-y) contains supplementary material, which is available to authorized users.

Hyperbaric Oxygen Therapy for Complications in Nipple-Sparing Mastectomy with Breast Reconstruction: A Systematic Review

“…These methods, which aim to enhance blood flow and tissue preconditioning, offer less invasive and infrastructure-dependent solutions. Discussing these alternatives with the patient can assist in determining the most suitable option for the individual circumstances [ 47 , 48 , 49 , 50 ]. There is a clear directive for future studies to determine the most effective timing and regimen for HBOT, evaluate its long-term impacts on patient recovery, and investigate its cost-effectiveness and accessibility.…”

A randomised controlled feasibility trial to evaluate local heat preconditioning on wound healing after reconstructive breast surgery: the preHEAT trial

“…all participants with a recorded outcome were included in the analysis according to the treatment group to which they were randomised regardless of treatment actually received. Please see Cro et al for full details of the statistical analysis plan [8].…”

“…Secondary feasibility objectives included estimating the recruitment rate and 30–40 day follow-up; to assess adherence with the heating protocol; to estimate the treatment effect on length of hospital stay and to estimate the rates of surgical versus conservative management of skin necrosis. Further details of the trial can be found in the protocol [8] .…”

Heat Preconditioning Protects Skin Pressure Injury and Reduces Incidence of Intraoperatively Acquired Pressure Ulcers in Both Humans and Animals

“…10 Recently, several studies showed that HPC reduces necrosis of the surrounding skin tissue after breast reconstruction. 11,12 The molecular mechanism for these effects is thought to be related to heat shock proteins (HSPs), 11 although this hypothesis has not yet been fully investigated. Among the many HSPs, HSP27 appears to participate in the anti-apoptosis response and protects the heart and kidney from ischemia/reperfusion injury.…”