Dataset Information

Prescribed exercise regimen versus usual care and hypochlorous acid wound solution versus placebo for treating venous leg ulcers: study protocol for a randomised controlled trial (Factorial4VLU).

ABSTRACT:

Introduction

Compression is the mainstay of treatment for venous leg ulcers (VLUs) and there are few effective adjuvant treatments. There is only observational evidence supporting the use of hypochlorous acid (HOCl) as a topical wound solution on VLU and some limited randomised evidence for the effect of a prescribed regimen of exercise.

Methods and analysis

The Factorial4VLU trial is a pragmatic, blinded, factorial randomised controlled trial, with 380 participants receiving either a prescribed exercise regimen compared with usual care and either active HOCl wound solution or placebo wound solution at each dressing change for up to 24 weeks. All participants will receive compression therapy. The primary outcome is the proportion of participants with healed VLU at 12 weeks after randomisation as adjudicated by blinded review of ulcer photographs. Secondary outcomes are proportion healed at 24 weeks, time to healing, estimated change in ulcer area, change in 2-Minute Walk Test, change in health-related quality of life, incidence of infection and incidence of all-cause adverse events. If either of the interventions shows a statistically significant positive difference on healing outcomes, cost-effectiveness will be modelled using a health service perspective.

Ethics and dissemination

The Factorial4VLU trial received ethical approval from the Northern B Health and Disability Ethics Committee. We plan to publish the results within 1?year of trial completion and will include the results on the trial registration page.

Trial registration numbers

Australia and New Zealand Clinical Trials Register (http://www.anzctr.org.au) (ACTRN12620000116921); Universal Trial Number (WHO) (U1111-1236-2997).

SUBMITTER: Jull A

PROVIDER: S-EPMC7896607 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prescribed exercise regimen versus usual care and hypochlorous acid wound solution versus placebo for treating venous leg ulcers: study protocol for a randomised controlled trial (Factorial4VLU).

Jull Andrew A Wadham Angela A Bullen Chris C Parag Varsha V Parsons John G M JGM Laking George G Waters Jill J Klonizakis Markos M O'Brien Jane J

BMJ open 20210218 2

<h4>Introduction</h4>Compression is the mainstay of treatment for venous leg ulcers (VLUs) and there are few effective adjuvant treatments. There is only observational evidence supporting the use of hypochlorous acid (HOCl) as a topical wound solution on VLU and some limited randomised evidence for the effect of a prescribed regimen of exercise.<h4>Methods and analysis</h4>The Factorial4VLU trial is a pragmatic, blinded, factorial randomised controlled trial, with 380 participants receiving eith ...[more]

PMID: 33602710

Similar Datasets

Project description:ImportanceExercise is recommended as an adjuvant treatment for venous leg ulceration (VLU) to improve calf muscle pump function. However, the association of exercise with VLU healing has not been properly aggregated, and the effectiveness of different exercise interventions has not been characterized.ObjectiveTo summarize the association of different exercise interventions with VLU healing when used as an adjuvant to any form of compression.Data sourcesThe Cochrane Controlled Trials Register, MEDLINE, Embase, CINAHL, PsycInfo, and SCOPUS databases were searched through October 9, 2017.Study selectionRandomized clinical trials (RCTs) of any exercise compared with no exercise in participants with VLU were included, where compression was used as standard therapy and a healing outcome was reported. Independent title screening and full text review by 2 authors (A.J., J.S.) with appeal to a third author (J.P.) if disagreement was unresolved. Of the 519 articles screened, a total of 6 (1.2%) studies met the inclusion criteria for systematic review, including 5 for meta-analysis.Data extraction and synthesisIndependent quality assessment for Cochrane risk of bias and data extraction by 2 authors with appeal to third author if disagreement unresolved (PRISMA). Data pooled using fixed effects model.Main outcomes and measuresThe a priori primary outcome was any healing outcome (proportion healed, time to healing, or change in ulcer area). Secondary outcomes (adverse events, costs, and health-related quality of life) were only collected if a primary outcome was reported.ResultsSix RCTs were identified and 5 (190 participants) met inclusion criteria for meta-analysis. The exercise interventions were progressive resistance exercise alone (2 RCTs, 53 participants) or combined with prescribed physical activity (2 RCTs, 102 participants), walking only (1 RCT, 35 participants), or ankle exercises (1 RCT, 40 participants). Overall, exercise was associated with increased VLU healing at 12 weeks although the effect was imprecise (additional 14 cases healed per 100 patients; 95% CI, 1-27 cases per 100; P = .04). The combination of progressive resistance exercise plus prescribed physical activity appeared to be most effective, again with imprecision (additional 27 cases healed per 100 patients; 95% CI, 9-45 cases per 100; P = .004).Conclusions and relevanceThe evidence base may now be sufficiently suggestive for clinicians to consider recommending simple progressive resistance and aerobic activity to suitable patients with VLU while further research is produced.

Project description:ObjectiveTo review the evidence of effectiveness of dressings applied to venous leg ulcers.DesignSystematic review and meta-analysis.Data sourcesHand searches of journals and searches of electronic databases, conference proceedings, and bibliographies up to April 2006; contacts with dressing manufacturers for unpublished studies.Studies reviewedAll randomised controlled trials that evaluated dressings applied to venous leg ulcers were eligible for inclusion. Data from eligible studies were extracted and summarised independently by two reviewers using a data extraction sheet. Methodological quality was assessed independently by two reviewers.ResultsThe search strategy identified 254 studies; 42 of these fulfilled the inclusion criteria. Hydrocolloids were no more effective than simple low adherent dressings used beneath compression (eight trials; relative risk for healing with hydrocolloid 1.02, 95% confidence interval 0.83 to 1.28). For other comparisons, insufficient evidence was available to allow firm conclusions to be drawn. None of the dressing comparisons showed evidence that a particular class of dressing healed more ulcers. Some differences existed between dressings in terms of subjective outcome measures and ulcer healing rates. The results were not affected by the size or quality of trials or the unit of randomisation. Insufficient data were available to allow conclusions to be drawn about the relative cost effectiveness of different dressings.ConclusionsThe type of dressing applied beneath compression was not shown to affect ulcer healing. The results of the meta-analysis showed that applying hydrocolloid dressings beneath compression produced no benefit in terms of ulcer healing compared with applying simple low adherent dressings. No conclusive recommendations can be made as to which type of dressing is most cost effective. Decisions on which dressing to apply should be based on the local costs of dressings and the preferences of the practitioner or patient.

Project description:BACKGROUND:Venous leg ulcers (VLUs) can take many months to heal and 25% fail to heal. The main treatment for venous leg ulcers is compression therapy and few additional therapies exist. Two previous trials indicated that low-dose aspirin may improve healing time, but these trials were insufficiently robust. METHODS:A multi-centred, pilot, phase II, randomised, double blind, parallel-group, placebo-controlled, efficacy trial (RCT) was conducted to determine: if aspirin improves VLU healing time; the safety of aspirin in this population; treatment compliance; and the feasibility of recruitment to a phase III trial. We recruited patients from secondary care who were aged ??18?years, had a chronic VLU and not regularly taking aspirin. Participants were randomly assigned (1:1) to receive 300?mg of daily aspirin or placebo in addition to standard care, which consisted of multi component compression therapy aiming to deliver 40?mmHg at the ankle where possible. The randomisation list was stratified by ulcer size (??5?cm2 or?>?5?cm2). The primary endpoint was time to ulcer healing, which was defined as 'complete epithelial healing in the absence of scab (eschar) with no dressing required'. Safety outcomes were assessed in all participants who received at least one dose of the study drug. RESULTS:Twenty-seven patients were recruited from eight sites (target 100 patients). A short time-frame to recruit and a large number of patients failing to meet the eligibility criteria were the main barriers to recruitment. There was no evidence of a difference in time to healing of the reference ulcer following adjustment for log ulcer area and duration (hazard ratio 0.58, 95% confidence interval 0.18 to 1.85; p?=?0.357). One expected serious adverse event related to aspirin was recorded. A number of options to improve recruitment were explored. CONCLUSIONS:There was no evidence that aspirin was effective in expediting the healing of chronic VLUs. However, the analysis was underpowered due to the low number of participants recruited. The trial design would require substantial amendment in order to progress to a phase III (effectiveness) trial. TRIAL REGISTRATION:Clinicaltrials.gov, NCT02333123. Registered on 5 November 2014.

Project description:BackgroundThe frequency of skin ulceration makes an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. This is an update of a previously published Cochrane Review.ObjectivesTo assess the clinical effectiveness and harms of interventions for treating leg ulcers in people with sickle cell disease.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We searched LILACS (1982 to January 2020), ISI Web of Knowledge (1985 to January 2020), and the Clinical Trials Search Portal of the World Health Organization (January 2020). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 13 January 2020; date of the last search of the Cochrane Wounds Group Trials Register: 17 February 2017.Selection criteriaRandomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment.Data collection and analysisTwo authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. We used GRADE to assess the quality of the evidence.Main resultsSix studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl® cream, arginine-glycine-aspartic acid (RGD) peptide dressing and topical antibiotics). No trials on non-pharmaceutical interventions were included in the review. All trials had an overall unclear or high risk of bias, and drug companies sponsored four of them. We were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the units of randomisation and analysis. Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, only arginine butyrate showed a reduction of ulcer size compared with a control group, mean reduction -5.10 cm² (95% CI -9.65 to -0.55), but we are uncertain whether this reduces ulcer size compared to standard care alone as the certainty of the evidence has been assessed as very low. Three trials reported on complete leg ulcer closure (isoxsuprine, arginine butyrate, RGD peptide matrix; very low quality of evidence). None reported a clinical benefit. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; incidence of amputation or harms.Authors' conclusionsGiven the very low quality of the evidence identified in this updated Cochrane Review we are uncertain whether any of the assessed pharmaceutical interventions reduce ulcer size or result in leg ulcer closure in treated participants compared to controls. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having an unclear or high risk of bias. The harm profile of the all interventions remains inconclusive.

Dataset Information

Prescribed exercise regimen versus usual care and hypochlorous acid wound solution versus placebo for treating venous leg ulcers: study protocol for a randomised controlled trial (Factorial4VLU).

Introduction

Methods and analysis

Ethics and dissemination

Trial registration numbers

Publications

Prescribed exercise regimen versus usual care and hypochlorous acid wound solution versus placebo for treating venous leg ulcers: study protocol for a randomised controlled trial (Factorial4VLU).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure