CellulitisPhase 3NVPNCT07665476
Naproxen Versus Placebo as Adjunct Treatment of Cellulitis
A Phase 3 study testing enteric-coated naproxen and Cephalexin Tablets in people with Cellulitis and Skin Disease, Infectious, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cellulitis, Skin Disease, Infectious, Infection
- What is being tested?
- enteric-coated naproxen and Cephalexin Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 884 participants
- Where
- 1 siteCanada
- Study dates
- 1 Nov 2026to 1 Dec 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adults (age ≥18 years)
- diagnosed with cellulitis and
- determined by the treating physician to be eligible for outpatient treatment with oral cephalexin
Who cannot join
- 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;
Show all 23Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site
The Ottawa Hospital
Ottawa, Ontario, K1y 4E9
Krishan Yadav, 613-798-5555, kyadav@toh.ca
Gabriel Sandino-Gold, gsandino@ohri.ca
About this study
Official title: Naproxen Versus Placebo as Adjunct Treatment of Cellulitis: A Randomized Controlled 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.
Read the detailed description
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.
- Being tested
- enteric-coated naproxen, Cephalexin Tablets, Placebo
- Keywords
- Infectious Diseases, Emergency Medicine, Cellulitis, naproxen, antibiotics, oral antibiotics, cephalexin, anti-inflammatories
- Medical subject headings
- Cellulitis, Skin Diseases, Infectious, Infections, Soft Tissue Infections, Communicable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enteric-coated naproxenDrug
Also called naproxen EC, naproxen
500 mg naproxen PO BID for 7 days
Cephalexin TabletsDrug
Also called Cephalexin
500 mg PO QID for 7 days
PlaceboDrug
Placebo tablets PO BID x 7 days
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Cephalexin Tablets; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: within 72 hours
Secondary outcomes (10)
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).
Measured: 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.
Measured: 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
Measured: Within 7 days
Number of Participants with Clinical Cure
Defined as absence of erythema, pain and fever
Measured: 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
Measured: 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.
Measured: 90 days
Number of participants with unplanned visits to a healthcare provider for cellulitis
Visits to ED, family doctor or walk in clinic
Measured: 90 days
Number of Participants with an Unplanned hospitalization for cellulitis
within 30 and 90 days.
Measured: 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.
Measured: 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
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2026
- Study start1 Nov 2026 (estimated)
- Primary completion1 Dec 2030 (estimated)
- Study completion1 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CellulitisStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The investigators will conduct a parallel-arm double-blind, individually randomized trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 884 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- The Ottawa Hospital Academic Medical Association, l'Association Médicale Universitaire Montfort (AMUM)
- Responsible party
- Sponsor
- Investigators
- Krishan Yadav, MD, MSc, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07665476
- Sponsor's protocol ID
- 20260315-01T
- Acronym
- NVP
- Status last verified
- Oct 2026
- First submitted
- 18 Jun 2026
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD requests can be submitted to the Investigator and will be reviewed on a case by case basis.
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Naproxen Versus Placebo as Adjunct Treatment of Cellulitis: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07665476
- Acronym / sponsor ID
- NVP / 20260315-01T
- Keywords
- Infectious Diseases, Emergency Medicine, Cellulitis, naproxen, antibiotics, oral antibiotics, cephalexin, anti-inflammatories
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 884 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- The Ottawa Hospital Academic Medical Association, l'Association Médicale Universitaire Montfort (AMUM)
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 1 Dec 2030 (estimated)
- Study completion
- 1 Dec 2031 (estimated)
- First posted
- 24 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The investigators will conduct a parallel-arm double-blind, individually randomized trial
| Arm | Type | Receives |
|---|---|---|
| Naproxen + Cephalexin | Experimental | Drug: enteric-coated naproxen, Drug: Cephalexin Tabletsseven-day medication package of naproxen 500 mg to be taken orally twice daily plus cephalexin antibiotic 500 mg four times daily. |
| Placebo + Cephalexin | Active comparator | Drug: Cephalexin Tablets, Drug: Placeboseven-day medication package of placebo to be taken orally twice daily plus cephalexin antibiotic 500 mg four times daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- adults (age ≥18 years)
- diagnosed with cellulitis and
- determined by the treating physician to be eligible for outpatient treatment with oral cephalexin
Key exclusion criteria (23 listed)
- 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.
- Age <18 years;
- Patient already taking oral antibiotics or NSAIDs;
- Treating physician decides IV antibiotics are required;
- Skin abscess requiring incision and drainage;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| enteric-coated naproxenAlso: naproxen EC, naproxen500 mg naproxen PO BID for 7 days | Drug | Naproxen + Cephalexin |
| Cephalexin TabletsAlso: Cephalexin500 mg PO QID for 7 days | Drug | Naproxen + Cephalexin, Placebo + Cephalexin |
| PlaceboPlacebo tablets PO BID x 7 days | Drug | Placebo + Cephalexin |
Primary outcome
Number of Participants with Early Clinical Response Assessed by Change in Lesion Area (cm²)
Time frame: within 72 hours
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.
10 secondary outcomes
Number of Participants with Oral antibiotic treatment failure
Time frame: between 3-7 days
Pain Measured Using the Numeric Rating Scale (0-10)
Time frame: Evaluated at day 0, 3, 8 and 30
Number of Participants with an Antibiotic switch
Time frame: Within 7 days
Number of Participants with Clinical Cure
Time frame: Evaluated at day 8 and 30
Recurrence
Time frame: Evaluated at day 90
Health-Related Quality of Life Measured Using the EuroQol 5-Dimension 5-Level (EQ-5D-5L)
Time frame: 90 days
Number of participants with unplanned visits to a healthcare provider for cellulitis
Time frame: 90 days
Number of Participants with an Unplanned hospitalization for cellulitis
Time frame: 90 days
Use of (i) acetaminophen; (ii) opioids; and (iii) corticosteroids
Time frame: Evaluated at day 3, 8 and 30.
Number of Participants with medication adherence
Time frame: 7 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Individual participant dataSharing planned: No. IPD requests can be submitted to the Investigator and will be reviewed on a case by case basis.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Krishan Yadav, MD, MSc principal investigator
Ottawa Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing enteric-coated naproxen and Cephalexin Tablets in people with Cellulitis and Skin Disease, Infectious, run by Ottawa Hospital Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Krishan Yadav, MD, MSc (613-798-5555 ext. 19489, kyadav@toh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Early Clinical Response Assessed by Change in Lesion Area (cm²) (time frame: within 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.