High-dose vs. Standard-dose Cephalexin for Cellulitis

December 4, 2024 updated by: Ottawa Hospital Research Institute

High-dose Cephalexin for Cellulitis: A Pilot Randomized Controlled Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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:

  1. New fever (temperature ≥ 38.0C) 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)

The secondary effectiveness outcomes are:

  1. Clinical cure (no erythema, pain and fever) at day 7
  2. Clinical response (≥20% reduction in area of erythema compared to baseline) at day 3
  3. Adverse events (e.g. vomiting, diarrhea, rash) at 14-day telephone follow-up
  4. Unplanned i) return ED visits; and ii) hospitalization at 14-day telephone follow-up

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.

Study Type

Interventional

Enrollment (Actual)

69

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1Y 4E9
        • The Ottawa Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

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:

  1. Age <18 years
  2. Patient already taking oral antibiotics
  3. Treating physician decides that intravenous therapy is required
  4. Abscess requiring an incision and drainage or needle aspiration procedure
  5. Known prior cellulitis secondary to methicillin-resistant Staphylococcus aureus
  6. Cellulitis secondary to a human or animal bite wound
  7. Surgical site infection
  8. Malignancy and currently being treated with chemotherapy
  9. Febrile neutropenia (temperature >=38C plus absolute neutrophil count <500 cells/uL)
  10. Solid organ or bone marrow transplant recipient
  11. Renal impairment with creatinine clearance <30 mL/min
  12. Pregnant or breastfeeding
  13. Allergy to cephalosporins or history of anaphylaxis to penicillin
  14. Inability to provide consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High Dose Cephalexin
The intervention is high-dose cephalexin (1000mg PO QID) for seven days
Drug: Cephalexin
1000 mg PO QID for 7 days
Other Names:
  • High-dose cephalexin
Active Comparator: Standard Dose Cephalexin
The comparator is standard-dose cephalexin (500mg PO QID) plus oral placebo for seven days
Drug: Cephalexin + placebo
500 mg PO QID plus oral placebo for 7 days
Other Names:
  • Standard-dose cephalexin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient Recruitment Rate
Time Frame: 6 months
% of patients recruited into the trial
6 months
Oral Antibiotic Treatment Failure
Time Frame: Each patient was assessed for oral antibiotic treatment failure at the day 3 and day 7 follow-ups

% 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)
Each patient was assessed for oral antibiotic treatment failure at the day 3 and day 7 follow-ups

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Unplanned ED Visits or Hospitalization
Time Frame: 14 days
% of patients with unplanned i) return ED visits; and ii) hospitalization, measured via 14-day telephone follow-up
14 days
Ability to Approach Eligible Patients
Time Frame: 6 months
% of eligible patients that were identified as being eligible but missed (staff was unable to approach to recruit in trial)
6 months
Assessment of Blinding
Time Frame: Patient were asked which dose of cephalexin they believe they received during the day 7 follow-up

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.
Patient were asked which dose of cephalexin they believe they received during the day 7 follow-up
Protocol Adherence
Time Frame: 7 days
% of patients that are adherent to allocated treatment for 7 days
7 days
Loss to Follow-up
Time Frame: Determined at final follow-up (day 14) if lost 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
Determined at final follow-up (day 14) if lost to follow-up
Clinical Cure
Time Frame: Assessed for clinical cure at day 7and day 14 follow-up
% of patients with clinical cure (no erythema, pain and fever) at days 7 and 14
Assessed for clinical cure at day 7and day 14 follow-up
Adverse Events
Time Frame: 14 days
% of patients with adverse events (e.g. vomiting, diarrhea, rash) at 14-days measured via telephone follow-up
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ottawa Hospital Research Institute

Collaborators

The Ottawa Hospital Academic Medical Association
Canadian Association of Emergency Physicians

Investigators

  • Principal Investigator: Krishan Yadav, MD, MSc, Ottawa Hospital Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 16, 2021

Primary Completion (Actual)

February 23, 2022

Study Completion (Actual)

February 23, 2022

Study Registration Dates

First Submitted

June 30, 2020

First Submitted That Met QC Criteria

July 9, 2020

First Posted (Actual)

July 15, 2020

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

December 4, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20200175

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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