Clinical trial NCT04471246: High-dose vs. Standard-dose Cephalexin for Cellulitis
Official title: High-dose Cephalexin for Cellulitis: A Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cellulitis
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: The Ottawa Hospital Academic Medical Association
name: Canadian Association of Emergency Physicians
First posted: 2020-07-15
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The Investigators will conduct a parallel arm double-blind randomized controlled pilot trial.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Patient Recruitment Rate
timeFrame: 6 months
measure: Oral Antibiotic Treatment Failure
timeFrame: Each patient was assessed for oral antibiotic treatment failure at the day 3 and day 7 follow-ups
Secondary outcomes:
measure: Ability to Approach Eligible Patients
timeFrame: 6 months
measure: Assessment of Blinding
timeFrame: Patient were asked which dose of cephalexin they believe they received during the day 7 follow-up
measure: Protocol Adherence
timeFrame: 7 days
measure: Loss to Follow-up
timeFrame: Determined at final follow-up (day 14) if lost to follow-up
measure: Clinical Cure
timeFrame: Assessed for clinical cure at day 7and day 14 follow-up
measure: Adverse Events
timeFrame: 14 days
measure: Unplanned ED Visits or Hospitalization
timeFrame: 14 days
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Krishan Yadav, MD, MSc
role: PRINCIPAL_INVESTIGATOR
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