The DEXACELL Trial – a protocol for a pragmatic, multicentre, double-blind, placebo-controlled, randomised, parallel group, phase 3 superiority trial to assess the effectiveness and cost-effectiveness of DEXAmethasone as an adjunctive therapy for the management of CELLulitis in adults presenting to urgent secondary care in the UK

Introduction:

Cellulitis is a common bacterial skin infection causing significant pain, swelling, and impact on daily activities, frequently leading to emergency department presentations and hospital admissions. While antibiotics are the mainstay of treatment, they do not directly address inflammation, often resulting in persisting or worsening symptoms in the initial days. Corticosteroids, with their potent anti-inflammatory effects, have shown benefit in other acute infections but are not currently standard care for patients with cellulitis. This trial aims to determine if adjunctive oral dexamethasone can reduce pain and improve outcomes in adults with cellulitis presenting to UK urgent secondary care settings.

Methods and analysis:

This is a pragmatic, multicentre, double-blind, placebo-controlled, randomised, parallel group, phase 3 superiority trial, with an internal pilot and parallel health economic evaluation. Adult patients (≥16 years) with a clinical diagnosis of cellulitis (at any body site except the orbit) presenting to urgent secondary care will be screened for eligibility. 450 participants will be randomised (1:1) to receive either two 8 mg doses of oral dexamethasone or matched placebo, administered approximately 24 hours apart, in addition to standard antibiotic therapy. The primary outcome is total pain experienced over the first 3 days post-randomisation, calculated using the standardised area under the curve (AUC) from pain scores (Numerical Rating Scale 0-10) across up to seven timepoints. Secondary outcomes include health-related quality of life (EQ-5D-5L), patient global impression of improvement, analgesia and antibiotic usage, hospital (re)admissions, complications, unscheduled healthcare use, cellulitis recurrence, and cost-effectiveness at 90 days. The primary estimand will apply a treatment policy approach to intercurrent events.

Ethics and dissemination

The trial has received ethical approval from South Central – Oxford B Research Ethics Committee (reference; 24/SC/0289) and will be conducted in compliance with GCP and applicable regulations. Informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed publications and conference presentations, and to patient groups and relevant clinical guideline committees.

Trial registration

ISRCTN76873478. Current protocol version 5.0, 7th January 2025.

Strengths and limitations of this study

• This trial employs a robust double-blind, placebo-controlled design to minimise bias in assessing a subjective primary outcome (patient-reported pain).

• The pragmatic nature of the trial, recruiting from diverse urgent secondary care settings, with additional incentives to recruit from minoritised groups, aims to enhance the generalisability of findings to real-world clinical practice.

• Comprehensive follow-up to 90 days allows for assessment of both short-term symptom relief and longer-term impacts on healthcare utilisation and recurrence.

• The inclusion of a parallel health economic evaluation will provide crucial information on the cost-effectiveness of adjunctive dexamethasone.

• Potential variability in’usual care’ antibiotic regimens across sites, while reflecting real-world practice, is a possible limitation, which is accounted for in the pragmatic design.