A Phase 3 interventional study of enteric-coated naproxen and Cephalexin Tablets in Cellulitis, Skin Disease, Infectious and Infection, sponsored by Ottawa Hospital Research Institute. Not yet recruiting at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-20.
Sponsored by Ottawa Hospital Research Institute · Phase 3, Interventional, and Treatment
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.
Cellulitis is a common bacterial skin infection and a frequent cause of emergency department visits in Canada. Standard management involves antibiotic therapy; however, patients often experience significant pain, erythema, and swelling that can impair quality of life and productivity. There is increasing evidence that inflammation contributes to these symptoms, suggesting that adjunct anti-inflammatory therapy may improve recovery.
Non-steroidal anti-inflammatory drugs (NSAIDs), such as naproxen, may reduce inflammation and improve symptom resolution when used alongside antibiotics. Prior randomized trials and meta-analyses have suggested a potential benefit in early clinical response; however, these studies were limited by small sample sizes and methodological constraints. As a result, there remains uncertainty regarding the effectiveness and safety of NSAIDs as adjunct therapy for cellulitis.
This study is a multicentre, double-blind, randomized controlled trial designed to evaluate the impact of adjunct naproxen on clinical outcomes in adult patients with cellulitis receiving standard antibiotic therapy. Participants will be randomly assigned in a 1:1 ratio to receive either naproxen or placebo in addition to oral antibiotics for 7 days. The trial will be conducted at multiple tertiary care emergency departments in Canada.
Participants will be followed longitudinally with assessments at prespecified time points to evaluate clinical response, patient-reported outcomes, healthcare utilization, and safety. Data will be collected through a combination of in-person, virtual, and telephone follow-up assessments.
The study is powered to detect a clinically meaningful difference in early response between treatment groups. Analyses will be conducted using an intention-to-treat approach, with regression-based methods used to compare outcomes between groups.
Findings from this study are expected to provide high-quality evidence regarding the role of NSAIDs as adjunct therapy for cellulitis and may inform future clinical practice guidelines and decision-making in emergency and outpatient care settings.
160 studies on the registry are indexed under Cellulitis; 14 are open to participants now.
This study's planned enrollment of 884 is above the median of 157 across 124 interventional studies indexed under Cellulitis.
Browse Cellulitis studies →Ottawa Hospital Research Institute is the lead sponsor of 547 studies on the registry; 99 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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:
Exclusion criteria (i) through (s) are known to NSAIDs.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
500 mg naproxen PO BID for 7 days
Also known as: naproxen EC, naproxen
500 mg PO QID for 7 days
Also known as: Cephalexin
Placebo tablets PO BID x 7 days
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.
Time frame: within 72 hours
Number of Participants with Oral antibiotic treatment failure
Defined as a change in antibiotic (change in class of oral antibiotic or step up to IV therapy) between 3-7 days due to worsening infection. Criteria for worsening infection: (1) New fever (temperature ≥38.0ºC) or persistent fever at follow-up; (2) Increasing area of erythema (in cm2) ≥20% from baseline; or (3) Increasing pain ≥2 points from baseline (using the Numeric Rating Scale).
Time frame: between 3-7 days
Pain Measured Using the Numeric Rating Scale (0-10)
Pain will be assessed using the Numeric Rating Scale (NRS), an 11-point scale ranging from 0 to 10. On the Numeric Rating Scale, 0 represents no pain and 10 represents the worst possible pain. Higher scores indicate worse pain.
Time frame: Evaluated at day 0, 3, 8 and 30
Number of Participants with an Antibiotic switch
Defined as an unplanned antibiotic change (change in class of oral antibiotic or step up to IV therapy) within 7 days that did not meet worsening infection criteria and treatment failure
Time frame: Within 7 days
Number of Participants with Clinical Cure
Defined as absence of erythema, pain and fever
Time frame: Evaluated at day 8 and 30
Recurrence
Number of patients that had a recurrence of infection at day 90, defined as development of a new skin and soft tissue infection (cellulitis or skin abscess) at the same or different anatomic site
Time frame: Evaluated at day 90
Health-Related Quality of Life Measured Using the EuroQol 5-Dimension 5-Level (EQ-5D-5L)
Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) instrument. The EQ-5D-5L descriptive system includes five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with five levels of severity ( 1- no problems, 2 - slight problems, 3 - moderate problems, 4 - severe problems and 5 - extreme problems). A lower score indicates a better outcome. The instrument also includes a visual analogue scale (EQ-VAS) ranging from 0 (worst imaginable health) to 100 (best imaginable health), with higher scores indicating better self-rated health.
Time frame: 90 days
Number of participants with unplanned visits to a healthcare provider for cellulitis
Visits to ED, family doctor or walk in clinic
Time frame: 90 days
Number of Participants with an Unplanned hospitalization for cellulitis
within 30 and 90 days.
Time frame: 90 days
Use of (i) acetaminophen; (ii) opioids; and (iii) corticosteroids
Reporting if there is use of acetaminophen, opioids or corticosteroids during the study period.
Time frame: Evaluated at day 3, 8 and 30.
Number of Participants with medication adherence
with full adherence defined as patients who report taking all study medication over 7 days
Time frame: 7 days
Plan to share: No — IPD requests can be submitted to the Investigator and will be reviewed on a case by case basis.
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Naproxen
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