A Phase 4 interventional study of Cephalexin and Cephalexin + placebo in Cellulitis, sponsored by Ottawa Hospital Research Institute. Completed at 1 site in Canada. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-01-17.
Sponsored by Ottawa Hospital Research Institute · Phase 4, Interventional, and Treatment
Cellulitis is a painful bacterial infection of the skin and underlying tissue that needs antibiotic treatment. There are approximately 193,000 visits to Canadian emergency departments (EDs) each year for cellulitis. Emergency doctors who treat patients with cellulitis must decide on the correct antibiotic agent, dose, duration and frequency. Cellulitis is most commonly treated with the oral antibiotic cephalexin. However, there has been little research to guide doctors with respect to cellulitis treatment, which has led to an overuse of intravenous antibiotics. In addition, the current treatment failure rate of 20% is unacceptably high. When compared to standard-dose oral cephalexin, high-dose oral cephalexin may reduce treatment failure, which would help decrease the need for intravenous antibiotics and subsequent hospitalization. A well-designed clinical trial is necessary to determine if high-dose oral cephalexin reduces treatment failure for cellulitis patients. This pilot trial will determine the feasibility and design of such a clinical trial.
Background: Cellulitis is a common clinical condition that represents up to 3% of all emergency department (ED) visits. The current treatment failure rate is approximately 20%. This high treatment failure rate may be due to suboptimal dosing of cephalexin. The Investigators hypothesize that high-dose cephalexin may lead to lower rates of treatment failure and subsequently improved patient outcomes (less hospitalizations and avoidance of intravenous antibiotics)
Rationale: Before embarking on a large, multicenter trial, it is essential to conduct a smaller pilot to test and refine study procedures and to demonstrate feasibility.
Methods:
Design: The investigators will conduct a parallel arm double-blind randomized controlled pilot trial at the Civic and General campus ED of The Ottawa Hospital (TOH). The study will operate seven days a week from 0800 to 2000 over a 6-month timeframe. TOH Pharmacy will follow a randomization sequence and prepare study medication packages. Study medication packages will be dispensed to the patient by a registered nurse (RN).
Patients: Adult (age >=18 years) ED patient with non-purulent cellulitis determined by the treating emergency physician to be eligible for outpatient care with oral antibiotics.
Intervention: High-dose cephalexin (1000 mg PO QID) for seven days.
Comparator: Standard-dose cephalexin (500 mg PO QID) plus placebo for seven days.
Primary Feasibility Outcome: Patient recruitment rate (percentage of approached eligible patients who are successfully recruited). The goal is to recruit at least 29% of eligible patients.
Primary Effectiveness Outcome: 1. Oral antibiotic treatment failure, defined as a change in antibiotic (change in class of oral antibiotic or step up to intravenous therapy) within 7 days due to worsening infection, which is defined as:
The secondary effectiveness outcomes are:
Importance: This pilot trial will be the first to compare high-dose cephalexin to standard-dose cephalexin for ED patients with cellulitis. The results of this pilot randomized trial will help inform the design and implementation of a larger, multicenter randomized controlled trial to answer this important clinical question.
160 studies on the registry are indexed under Cellulitis; 14 are open to participants now.
This study's enrollment of 69 is below 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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Adults (age >=18 years) with non-purulent cellulitis determined by the treating emergency physician to be eligible for outpatient care with oral antibiotics.
Exclusion Criteria:
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.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The intervention is high-dose cephalexin (1000mg PO QID) for seven days
Drug: Cephalexin
The comparator is standard-dose cephalexin (500mg PO QID) plus oral placebo for seven days
Drug: Cephalexin + placebo
1000 mg PO QID for 7 days
Also known as: High-dose cephalexin
Drug page: Cephalexin
500 mg PO QID plus oral placebo for 7 days
Also known as: Standard-dose cephalexin
Patient Recruitment Rate
% of patients recruited into the trial
Time frame: 6 months
Oral Antibiotic Treatment Failure
% of patients with oral antibiotic treatment failure Oral antibiotic treatment failure, defined as a change in antibiotic (change in class of oral antibiotic or step up to intravenous therapy) within 7 days due to worsening infection, which is defined as: 1. New fever (temperature ≥ 38.0°C) or persistent fever at Day 3 follow up; or 2. Increasing area of erythema ≥20% from baseline; or 3. Increasing pain ≥2 points from baseline (numeric rating scale)
Time frame: Each patient was assessed for oral antibiotic treatment failure at the day 3 and day 7 follow-ups
Ability to Approach Eligible Patients
% of eligible patients that were identified as being eligible but missed (staff was unable to approach to recruit in trial)
Time frame: 6 months
Assessment of Blinding
The percentage of patients that correctly guessed their treatment allocation. To assess how well blinded the patients were to the medication they received, each was asked during the day 7 follow-up, after having finished their medication, to indicate which treatment they believe they received (500mg of 1000mg of cephalexin). Once unblinded to the allocation (after enrollment and follow-up complete), it was possible to determine which patients correctly guess the dose of medication they received.
Time frame: Patient were asked which dose of cephalexin they believe they received during the day 7 follow-up
Protocol Adherence
% of patients that are adherent to allocated treatment for 7 days
Time frame: 7 days
Loss to Follow-up
% of patients lost to follow-up at 14 days Patients were lost to follow-up if they did not attend any follow-up visit at days 3, 7 and 14
Time frame: Determined at final follow-up (day 14) if lost to follow-up
Clinical Cure
% of patients with clinical cure (no erythema, pain and fever) at days 7 and 14
Time frame: Assessed for clinical cure at day 7and day 14 follow-up
Adverse Events
% of patients with adverse events (e.g. vomiting, diarrhea, rash) at 14-days measured via telephone follow-up
Time frame: 14 days
Unplanned ED Visits or Hospitalization
% of patients with unplanned i) return ED visits; and ii) hospitalization, measured via 14-day telephone follow-up
Time frame: 14 days
Three randomized patients were excluded due to an alternat diagnosis, thus 66 moved forward for analysis (33 in each arm)
| Milestone | High Dose Cephalexin | Standard Dose Cephalexin |
|---|---|---|
| Started | 33 | 33 |
| Completed | 31 | 31 |
| Not completed | 2 | 2 |
| Withdrew: Lost to follow-up | 2 | 2 |
% of patients recruited into the trial
| percentage of eligible patients | Patients Identified as Eligible for the Trial |
|---|---|
| Patient Recruitment Rate | 51.5 |
% of patients with oral antibiotic treatment failure Oral antibiotic treatment failure, defined as a change in antibiotic (change in class of oral antibiotic or step up to intravenous therapy) within 7 days due to worsening infection, which is defined as: 1. New fever (temperature ≥ 38.0°C) or persistent fever at Day 3 follow up; or 2. Increasing area of erythema ≥20% from baseline; or 3. Increasing pain ≥2 points from baseline (numeric rating scale)
| percentage of enrolled in each arm | High Dose Cephalexin | Standard Dose Cephalexin |
|---|---|---|
| Oral Antibiotic Treatment Failure | 3.2 (0.6 to 16.2) | 12.9 (5.1 to 28.9) |
% of eligible patients that were identified as being eligible but missed (staff was unable to approach to recruit in trial)
| percentage of eligible patients | Patients Identified as Eligible for the Trial |
|---|---|
| Ability to Approach Eligible Patients | 14.2 |
The percentage of patients that correctly guessed their treatment allocation. To assess how well blinded the patients were to the medication they received, each was asked during the day 7 follow-up, after having finished their medication, to indicate which treatment they believe they received (500mg of 1000mg of cephalexin). Once unblinded to the allocation (after enrollment and follow-up complete), it was possible to determine which patients correctly guess the dose of medication they received.
| percentage of enrolled per arm | High-dose Group | Standard-dose Group |
|---|---|---|
| Assessment of Blinding | 33.3 | 60.1 |
% of patients that are adherent to allocated treatment for 7 days
| percentage of enrolled and analyzed | High-dose Group | Standard-dose Group |
|---|---|---|
| Protocol Adherence | 75.8 | 75.8 |
% of patients lost to follow-up at 14 days Patients were lost to follow-up if they did not attend any follow-up visit at days 3, 7 and 14
| percentage of enrolled per arm | High-dose Group | Standard-dose Group |
|---|---|---|
| Loss to Follow-up | 6.1 | 6.1 |
% of patients with clinical cure (no erythema, pain and fever) at days 7 and 14
| percentage of enrolled in each arm | High Dose Cephalexin | Standard Dose Cephalexin |
|---|---|---|
| Clinical cure at day 14 | 45.2 (29.2 to 62.2) | 38.7 (23.7 to 56.2) |
| Clinical cure at day 7 | 16.1 (7.1 to 32.6) | 6.5 (1.8 to 20.7) |
% of patients with adverse events (e.g. vomiting, diarrhea, rash) at 14-days measured via telephone follow-up
| percentage of enrolled in each arm | High Dose Cephalexin | Standard Dose Cephalexin |
|---|---|---|
| Nausea or vomiting | 9.7 (3.4 to 24.9) | 3.2 (0.6 to 16.2) |
| Diarrhea | 16.1 (7.1 to 32.6) | 6.5 (1.8 to 20.7) |
| Abdominal pain | 3.2 (0.6 to 16.2) | 0 (0 to 11) |
| Rash | 3.2 (0.6 to 16.2) | 6.5 (1.8 to 20.7) |
| Other | 6.5 (1.8 to 20.7) | 9.7 (3.4 to 24.9) |
| No adverse events to report | 61.3 (43.8 to 76.3) | 74.2 (56.8 to 86.3) |
% of patients with unplanned i) return ED visits; and ii) hospitalization, measured via 14-day telephone follow-up
| percentage of enrolled in each arm | High Dose Cephalexin | Standard Dose Cephalexin |
|---|---|---|
| Unplanned visit to family doctor within 14 days | 6.5 (1.8 to 20.7) | 6.5 (1.8 to 20.7) |
| Unplanned return to ED within 14 days | 22.6 (11.4 to 39.8) | 16.1 (7.1 to 32.6) |
| Unplanned hospitalization within 14 days | 0 (0 to 11) | 0 (0 to 11) |
Collected over Patients were assessed for adverse events during the day 7 and day 14 study follow-ups. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| High Dose Cephalexin | 0/31 (0%) | 0/31 (0%) | 12/31 (38.7%) |
| Standard Dose Cephalexin | 0/31 (0%) | 0/31 (0%) | 8/31 (25.8%) |
| Event | High Dose Cephalexin | Standard Dose Cephalexin |
|---|---|---|
| DiarrheaGastrointestinal disorders | 5/31 | 2/31 |
| Nausea or vomitingGastrointestinal disorders | 3/31 | 1/31 |
| OtherProduct Issues | 2/31 | 3/31 |
| RashSkin and subcutaneous tissue disorders | 1/31 | 2/31 |
| Abdominal painGastrointestinal disorders | 1/31 | 0/31 |
| Age, Categorical(Participants) | High Dose Cephalexin | Standard Dose Cephalexin | Total |
|---|---|---|---|
| <=18 years | 1 | 1 | 2 |
| Between 18 and 65 years | 19 | 22 | 41 |
| >=65 years | 13 | 10 | 23 |
| Age, Continuous(years) | High Dose Cephalexin | Standard Dose Cephalexin | Total |
|---|---|---|---|
| Median | 56 (34 to 71) | 57 (40 to 69) | 56 (37 to 70) |
| Sex: Female, Male(Participants) | High Dose Cephalexin | Standard Dose Cephalexin | Total |
|---|---|---|---|
| Female | 13 | 13 | 26 |
| Male | 20 | 20 | 40 |
| Race and Ethnicity Not Collected(Participants) | High Dose Cephalexin | Standard Dose Cephalexin | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(participants) | High Dose Cephalexin | Standard Dose Cephalexin | Total |
|---|---|---|---|
| Canada | 33 | 33 | 66 |
| BMI(kg/m2) | High Dose Cephalexin | Standard Dose Cephalexin | Total |
|---|---|---|---|
| Median | 30.4 (24.4 to 36.8) | 27.9 (23.4 to 31.6) | 29.1 (24.1 to 34.6) |
| Height(metres) | High Dose Cephalexin | Standard Dose Cephalexin | Total |
|---|---|---|---|
| Median | 1.72 (1.63 to 1.8) | 1.67 (1.59 to 1.79) | 1.7 (1.62 to 1.8) |
| Weight(kg) | High Dose Cephalexin | Standard Dose Cephalexin | Total |
|---|---|---|---|
| Median | 90 (76.5 to 106.5) | 80 (64 to 96.5) | 84.5 (74 to 100) |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Aug 2021 to primary completion in Feb 2022, 6 months.
Results were first posted in Jan 2025, 2 years 10 months after primary completion.
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Studies of the drug tested here: Cephalexin
Ottawa Hospital Research Institute →