High-Dose Cephalexin for Cellulitis

(HI-DOCC Trial)

Recruiting at 10 trial locations

Overseen By Gabriel Sandino-Gold

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Oral antibiotics, Chemotherapy

Disqualifiers: MRSA, Transplant, Renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 1 week

446 Participants Needed

Trial Summary

What is the purpose of this trial?

Cellulitis is a common condition diagnosed and managed in the ED that carries significant burden on healthcare systems globally. Cellulitis is the 8th most common reason patients present to an ED in Canada. Among middle-aged patients (45-64 years) it is the 5th most common reason to visit an ED. This disease is responsible for significant healthcare system burden due to high hospitalization rates and subsequent costs. The Investigators conducted a health records review at two large urban EDs in Ottawa, and found that 29.6% of patients with cellulitis are admitted to hospital. In a separate study, The investigators found that the mean cost of care to hospitalize cellulitis patients for IV antibiotics was $10,145 CDN.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking oral antibiotics.

What data supports the effectiveness of the drug cephalexin for treating cellulitis?

Research shows that cephalexin is effective in treating skin and soft tissue infections, including cellulitis, with a high success rate in studies comparing different formulations. However, one study indicated that cephalexin had a higher failure rate compared to other antibiotics for uncomplicated cellulitis, suggesting it may be less effective in some cases. ^{1 2 3 4 5}

Is high-dose cephalexin safe for treating cellulitis?

Cephalexin is generally safe for treating skin infections like cellulitis, with common side effects including mild skin reactions and stomach issues. In studies, only a small percentage of patients stopped treatment due to side effects. ^{1 2 6 7 8}

How does the drug cephalexin differ from other treatments for cellulitis?

High-dose cephalexin is unique for treating cellulitis as it can be administered orally, making it convenient for outpatient care, especially in children. It is effective against common bacteria causing skin infections, like Staphylococcus aureus and Streptococcus pyogenes, and offers a safe and effective option with flexible dosing schedules. ^{2 3 9 10 11}

Research Team

Krishan Yadav, MD

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

This trial is for adults over 18 with non-purulent cellulitis who can take oral antibiotics at home. It's not for those under 18, on current antibiotics, needing IV treatment or surgery, with a history of MRSA-related cellulitis, cephalosporin allergy, unable to consent, undergoing chemotherapy for cancer, having symptoms in both legs, from penetrating wounds or water exposure related infections or severe kidney issues.

Inclusion Criteria

I am 18 or older with cellulitis and can be treated with oral antibiotics at home.

Exclusion Criteria

My kidney function is significantly reduced.

I have an infection at a recent surgery site.

My doctor has prescribed IV antibiotics for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either high-dose or standard-dose cephalexin for seven days

1 week

1 visit (in-person) for initial assessment

Follow-up

Participants are monitored for treatment effectiveness and adverse events

4 weeks

3 visits (in-person) at days 3, 8, and 30

Treatment Details

Interventions

• Cephalexin

Trial Overview The HI-DOCC study tests whether high doses of Cephalexin are effective in treating cellulitis without hospital admission. The goal is to see if this approach can reduce the healthcare burden by managing more cases as outpatients.

Participant Groups

Group I: High Dose Cephalexin Experimental Treatment 1 Intervention

The intervention is high-dose cephalexin (1000mg PO QID) for seven days

Group II: Standard Dose Cephalexin Active Control 1 Intervention

The comparator is standard-dose cephalexin (500mg PO QID) plus oral placebo for seven days

Cephalexin is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Approved in European Union as Cefalexin for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Approved in Canada as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Approved in Switzerland as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

The Ottawa Hospital Academic Medical Association

Collaborator

Trials

24

Recruited

3,000+

Network of Canadian Emergency Researchers (NCER)

Collaborator

Trials

1

Recruited

450+

Findings from Research

In two randomized studies involving 343 patients, cephalexin hydrochloride was found to be as effective as cephalexin monohydrate for treating skin and soft tissue infections, with high response rates of 95.7% and 96.5% respectively.

Both formulations demonstrated a similar safety profile, with only 4.95% of patients experiencing adverse events, indicating that cephalexin hydrochloride is a safe and effective option for these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections. Kumar, A., Murray, DL., Hanna, CB., et al.[2021]

Cephalosporins are generally safe with fewer side effects compared to penicillins, and recent studies suggest that cross-reactivity in patients with penicillin allergies may not be a significant concern.

While modern cephalosporins have low nephrotoxicity, some can cause bleeding risks and gastrointestinal issues, particularly ceftriaxone and cefoperazone, which can lead to high biliary concentrations and potential Clostridium difficile infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of cephalosporins. Norrby, SR.[2018]

Cephalosporins are generally well tolerated antibiotics, with allergic reactions occurring in 0.9 to 3.2% of patients, and serious adverse effects are rare, affecting less than 1% of patients.

While cephalosporins are considered safe, subtle differences in their chemical structure can lead to specific adverse effects, necessitating ongoing monitoring for potential reactions, especially with the introduction of new agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of newer cephalosporins. An update. Thompson, JW., Jacobs, RF.[2018]

In a review of adverse reactions to various antibacterial drugs involving over 5,000 patients, cefotaxime had the highest side effect rate at 9.8%, while cefazolin had the lowest at 3.8%, indicating varying safety profiles among these antibiotics.

No significant intergroup differences in serious adverse effects were found, and no deaths were attributed to any of the drugs, suggesting that while side effects occur, they are generally manageable and not life-threatening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update of safety of cefotaxime. Childs, SJ., Kosola, JW.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cefadroxil in the management of facial cellulitis of odontogenic origin. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Outpatient management of moderate cellulitis in children using high-dose oral cephalexin. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Increased therapeutic failure for cephalexin versus comparator antibiotics in the treatment of uncomplicated outpatient cellulitis. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Ceftriaxone treatment of skin and soft tissue infections in a once daily regimen. [2013]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Side effects of cephalosporins. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Adverse effects of newer cephalosporins. An update. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Update of safety of cefotaxime. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Haemophilus influenzae cellulitis in an adult. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical and laboratory evaluation of cefamandole in infants and children. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Review of the new second-generation cephalosporins: cefonicid, ceforanide, and cefuroxime. [2019]