Naproxen Versus Placebo as Adjunct Treatment of Cellulitis

Starting soon · Phase 3 · Has a placebo group

Conditions studied: Cellulitis, Skin Disease, Infectious, Infection, Skin and Soft Tissue Infections (SSTIs)

In brief

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.

Key facts

Study ID

NCT07665476

Run by

Ottawa Hospital Research Institute

People needed

884

Starts

2026-09-01

Expected to finish

2031-12-01

Last updated by the study team

2026-07-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

• These are appropriate exclusions according to eligibility for treatment with naproxen in clinical practice, and the investigators believe that relatively few patients will be excluded.
• The investigators will exclude participants for any of the following reasons:
• Age <18 years;
• Patient already taking oral antibiotics or NSAIDs;
• Treating physician decides IV antibiotics are required;
• Skin abscess requiring incision and drainage;
• Known prior skin or soft tissue infection secondary to methicillin-resistant Staphylococcus aureus (MRSA);
• Cellulitis secondary to a human or animal bite;
• Penetrating wound or water exposure resulting in cellulitis;
• Surgical site infection;
• Pregnancy or breastfeeding;
• Prior gastric bypass surgery;
• Patients on dual antiplatelet therapy;
• Patients on warfarin, low molecular weight heparin, or direct oral anticoagulant therapy;
• 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.;
• History of gastric/duodenal ulcer or gastrointestinal bleeding in the past 12 months;
• 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;
• Known hyperkalemia documented on the electronic health record at any time within the past three months;
• Liver cirrhosis;
• Inflammatory bowel disease;
• History of asthma, urticaria or allergic reactions after taking NSAIDs or aspirin;
• Allergy to cephalosporins or history of anaphylaxis to penicillin; (u) Inability to provide informed consent.
• Exclusion criteria (i) through (s) are known contraindications to NSAIDs.

Where it is running

• The Ottawa Hospital — Ottawa, Ontario, Canada

Full record on ClinicalTrials.gov

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