title: Determining the Effectiveness of Fibrin Sealants in Reducing Complications in Patients Undergoing Lateral Neck Dissection (DEFeND): a randomised external pilot trial
Creators: name: Bajwa, Mandeep
Publisher: name: University of Liverpool Repository
Year: 2021

description: Background Complications after major surgery are a significant cause of morbidity and mortality. Neck Dissection (ND) is one of the most commonly performed major operations in Head and Neck Surgery (HNS). Significant surgical complications occur in approximately 10 – 40% of all patients. A systematic review and meta-analysis of randomised controlled trials (RCT) suggests that Fibrin Sealants (FS) may have potential clinical advantages in HNS through the reduction of complications, volume of wound drainage and retention time of the drains. So far, all RCTs have been single centre explanatory studies that lack external validity and are of variable quality. The paucity of high-quality pragmatic trials means that a surgical trial to determine the effectiveness of FS in reducing the rate and severity of complications in patients undergoing lateral neck dissection is warranted. The DEFeND randomised external pilot trial (REPT) will address critical questions on how well key components of the proposed study design work together as well as the feasibility of a definitive trial. Currently a Core Outcome Set (COS) for HNS does not exist and there is a paucity of patient centred outcome measures specific to HNS. A scoping review of surgical COS is proposed to guide the direction of future HNS outcomes research. Methods The trial design that is being piloted is that of a two arm, parallel group, superiority trial with block randomisation in a 1:1 allocation ratio. The interventional arm will constitute the application of FS (ARTISS, Baxter Healthcare Ltd) to the surgical wound following completion of ND in addition to standard of care (SoC). The control arm will constitute SoC alone. Patients will be recruited from two sites, Aintree University Hospital (AUH) and Queen Victoria Hospital (QVH). Eligible patients will include patients who require a lateral neck dissection with a minimum of three cervical nodal levels. Patients who require bilateral neck procedures or undergoing immediate reconstruction with free or regional flaps will be excluded. The outcomes being assessed are recruitment rate; screened to randomisation rate; fidelity of blinding process using blinding indices; number of missing or incomplete data entries; number of protocol deviations; number of losses to follow-up. A scoping review of surgical COS registered with the COMET database will be undertaken. Only COS in which patients or their carers are stakeholders will be included. The suitability of outcome measures proposed for the definitive DEFeND trial will also be discussed. Results Overall, the trial recruited ahead of time and target. Out of 101 eligible patients 48 (47.5%) were randomised successfully at a rate of 5.3 patients per month. Five patients were withdrawn from the trial before surgery due to a change in treatment plan that meant they were no longer eligible. Blinding of patients, Research Nurses and outcome assessors was effective as determined by blinding indices. Missing outcome data was low and there were no differences between treatment arm and site. Two significant protocol deviations were reported relating to the allocation reveal at a specific time point during surgery. Both occurred early in the trial and were not repeated after corrective and preventative actions. Two (4%) patients were lost to follow-up. The scoping review yielded 207 outcomes from 19 surgically relevant COS published between 2014 – 2020. Outcomes were classified (humanistic (71), complications (57), measurements (39), resource use (22), mortality (18)). Humanistic and complication outcomes were the most frequently utilised in surgical COS. Conclusion The DEFeND REPT has demonstrated that many components of the trial design work well together and a definitive pragmatic trial is feasible. Refinements in trial design and conduct are discussed and have the potential to improve the performance of the trial even further. The process has also revealed an important deficiency in patient centred outcomes that needs to be addressed before a definitive trial can be commenced. The validity and reliability of the Clavien-Dindo classification of surgical complications is discussed. Developing a COS for HNS trials is an important first step in identifying and developing patient centred outcomes. Consideration should be given to using patient reported outcome measures (PROM) for subjective core outcomes. This study has shown that PROMs are both acceptable and feasible in HNS trials.