Naproxen Versus Placebo as Adjunct Treatment of Cellulitis: A Randomized Controlled Trial

Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorOttawa Hospital Research Institute

About this trial

Cellulitis is a painful bacterial skin infection commonly seen in Canadian emergency departments. Cellulitis has a negative impact on patients' quality of life and productivity. While this is a bacterial infection, there is evidence inflammation also contributes to the disabling symptoms of pain, redness and swelling. Some studies have suggested that a nonsteroidal anti-inflammatory drug (NSAID) such as naproxen in addition to antibiotics may control inflammation and speed recovery. However, these studies have had too few patients to tell if there is a true benefit.

The investigators are proposing a randomized controlled trial of patients with cellulitis to compare oral naproxen (500 mg twice daily) plus oral antibiotics versus placebo plus oral antibiotics. The investigators will compare the proportion of patients who have an early clinical response (reduction in area of redness ≥20% at 72 hours), cure, treatment failure, adverse events, and hospital admission.

If naproxen proves to be superior to placebo, this simple, low-cost intervention will speed time to recovery with less pain for patients, and may potentially reduce treatment failure and time missed from activities. The results of this trial will help inform future cellulitis treatment guidelines.

Eligibility criteria

Qualifiers

adults (age ≥18 years) diagnosed with cellulitis and determined by the treating physician to be eligible for outpatient treatment with oral cephalexin.

Disqualifiers

These are appropriate exclusions according to eligibility for treatment with naproxen in clinical practice, and we believe that relatively few patients will be excluded. We will exclude participants for any of the following reasons: (a) Age <18 years; (b) Patient already taking oral antibiotics or NSAIDs; (c) Treating physician decides IV antibiotics are required; (d) Skin abscess requiring incision and drainage; (e) Known prior skin or soft tissue infection secondary to methicillin-resistant Staphylococcus aureus (MRSA); (f) Cellulitis secondary to a human or animal bite; (g) Penetrating wound or water exposure resulting in cellulitis; (h) Surgical site infection; (i) Pregnancy or breastfeeding; (j) Prior gastric bypass surgery; (k) Patients on dual antiplatelet therapy; (l) Patients on warfarin, low molecular weight heparin, or direct oral anticoagulant therapy; (m) Severe uncontrolled heart failure, or coronary artery bypass grafting (CABG) surgery within 14 days prior to the index visit, or planned CABG surgery within 21 days following the index visit.; (n) History of gastric/duodenal ulcer or gastrointestinal bleeding in the past 12 months; (o) Known kidney impairment with an estimated glomerular filtration rate <30 mL/min documented on the electronic health record at any time within the past three months; (p) Known hyperkalemia documented on the electronic health record at any time within the past three months; (q) Liver cirrhosis; (r) Inflammatory bowel disease; (s) History of asthma, urticaria or allergic reactions after taking NSAIDs or aspirin; (t) Allergy to cephalosporins or history of anaphylaxis to penicillin; (u) Inability to provide informed consent.

Trial design

Treatments tested in this trial

  • enteric-coated naproxen
  • Cephalexin Tablets
  • Placebo

Treatment groups

884 Participants
are divided into 2 treatment groups

Sponsors and collaborators

Ottawa Hospital Research Institute

Lead sponsor

The Ottawa Hospital Academic Medical Association

Collaborator

l'Association Médicale Universitaire Montfort (AMUM)

Collaborator