Naproxen Versus Placebo as Adjunct Treatment of Cellulitis

NCT07665476 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 20260315-01T
• Study Type: interventional
• Target: 884
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cellulitis; Skin Disease, Infectious; Infection; Skin and Soft Tissue Infections (SSTIs)

Keywords

Infectious Diseases; Emergency Medicine; Cellulitis; naproxen; antibiotics; oral antibiotics; cephalexin; anti-inflammatories

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Early Clinical Response Assessed by Change in Lesion Area (cm²)

  Early clinical response is defined as a reduction in lesion size (area of erythema) of at least 20% compared to baseline within 72 hours. Lesion size will be assessed by measuring the area of erythema in square centimeters (cm²). Linear dimensions of the lesion will be obtained using a disposable tape measure.

  within 72 hours

Secondary Outcomes (10)

• Number of Participants with Oral antibiotic treatment failure

  between 3-7 days

• Pain Measured Using the Numeric Rating Scale (0-10)

  Evaluated at day 0, 3, 8 and 30

• Number of Participants with an Antibiotic switch

  Within 7 days

• Number of Participants with Clinical Cure

  Evaluated at day 8 and 30

• Recurrence

  Evaluated at day 90

Study Arms (2)

Naproxen + Cephalexin

EXPERIMENTAL

seven-day medication package of naproxen 500 mg to be taken orally twice daily plus cephalexin antibiotic 500 mg four times daily.

Drug: enteric-coated naproxen; Drug: Cephalexin Tablets

Placebo + Cephalexin

ACTIVE COMPARATOR

seven-day medication package of placebo to be taken orally twice daily plus cephalexin antibiotic 500 mg four times daily.

Drug: Cephalexin Tablets; Drug: Placebo

Interventions

Cephalexin Tablets DRUG

500 mg PO QID for 7 days

Also known as: Cephalexin

Naproxen + Cephalexin; Placebo + Cephalexin

Placebo DRUG

Placebo tablets PO BID x 7 days

Placebo + Cephalexin

enteric-coated naproxen DRUG

500 mg naproxen PO BID for 7 days

Also known as: naproxen EC, naproxen

Naproxen + Cephalexin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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:

• 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;

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• The Ottawa Hospital Academic Medical Association: collaborator
• l'Association Médicale Universitaire Montfort (AMUM): collaborator

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1y 4E9, Canada

Location

MeSH Terms

Conditions

Cellulitis; Skin Diseases, Infectious; Infections; Soft Tissue Infections; Communicable Diseases

Interventions

Naproxen; Cephalexin

Condition Hierarchy (Ancestors)

Suppuration; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Diseases; Disease Attributes

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Krishan Yadav, MD, MSc

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Krishan Yadav, MD, MSc

CONTACT

613-798-5555; kyadav@toh.ca

Gabriel Sandino-Gold, BScHK

CONTACT

613-798-5555; gsandino@ohri.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be randomized (1:1) to naproxen versus placebo arms. The randomization sequence will be computer-generated by a statistician
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The investigators will conduct a parallel-arm double-blind, individually randomized trial

Study Record Dates

• First Submitted: June 18, 2026
• First Posted: June 24, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2031
• Last Updated: July 7, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)