High-Dose Cephalexin for Cellulitis

(HI-DOCC Trial)

Enrolling by invitation at 12 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a high dose of the antibiotic cephalexin compared to the standard dose for treating cellulitis, a common skin infection. The researchers aim to determine if a higher dose can speed up recovery and reduce hospital stays. Patients diagnosed with non-purulent cellulitis (a type of skin infection without pus) who can take antibiotics at home may qualify for this trial. As a Phase 4 trial, this research involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

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 is the safety track record for these treatments?

Research has shown that cephalexin, the treatment tested in this trial, is a commonly used antibiotic for skin infections like cellulitis. Many patients tolerate this drug well. Studies have found cephalexin effective in treating cellulitis, but there is a 20% chance that the oral treatment might not work, requiring a different medication.

The trial is testing a higher dose of cephalexin. Current research lacks specific safety information on this higher dose. However, since cephalexin is already widely used and this study is in a later phase, the treatment is likely generally well-tolerated. This suggests that major safety issues have not been common in earlier studies. It is always important to be aware of possible side effects and to discuss these with a healthcare provider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about high-dose cephalexin for cellulitis because it offers a potential improvement over the standard treatment. Most cellulitis treatments use a standard dose of antibiotics like cephalexin to combat bacterial infections. However, this high-dose approach delivers twice the usual amount, aiming to tackle infections more aggressively and possibly reduce the duration of symptoms. This could lead to faster recovery times and better outcomes for patients, making it a promising option worth investigating.

What evidence suggests that high-dose cephalexin might be an effective treatment for cellulitis?

This trial will compare high-dose cephalexin with standard-dose cephalexin for treating cellulitis. Research has shown that a higher dose of cephalexin can effectively treat cellulitis. Studies have found that this increased dosage can lead to better outcomes, such as a noticeable decrease in symptoms like redness, pain, and fever by the seventh day of treatment. Previous research suggests that regular doses of cephalexin might not work as well due to growing antibiotic resistance, making the higher dose a potentially better choice. The high-dose approach aims to lower the chance of treatment failure, helping more patients fully recover. This treatment has proven effective for cellulitis, helping many patients avoid more serious health issues. ^{1 2 3 4 6}

Who Is on the Research Team?

Krishan Yadav, MD

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9807092/

High-dose cephalexin for cellulitis: a pilot randomized ... The preliminary effectiveness outcomes are shown in Table 3. For the primary effectiveness outcome, oral antibiotic treatment failure ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04471246

High-dose vs. Standard-dose Cephalexin for Cellulitis The secondary effectiveness outcomes are: Clinical cure (no erythema, pain and fever) at day 7; Clinical response (≥20% reduction in area of erythema ...

3. impactfactor.org impactfactor.org/PDF/IJPCR/16/IJPCR,Vol16,Issue1,Article136.pdf

Effect of Cephalexin at High Dose in Patients with Cellulitis Cephalexin is routine antibiotic therapy; however, growing resistance necessitates greater dosages for improved effectiveness, requiring further.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36592299/

High-dose cephalexin for cellulitis: a pilot randomized ... The preliminary primary effectiveness outcome was oral antibiotic treatment failure. Results: Of 134 eligible participants approached for ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1341321X25002302

Evaluation of Cefazolin <3 g vs. 3 g Treatment Doses ... High-dose cefazolin was associated with a higher rate of clinical success in obese patients treated for cellulitis. The DOOR calculations showed ...

6. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2627970

Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole ... Addition of trimethoprim-sulfamethoxazole to cephalexin did not result in a statistically significant improvement in clinical cure for uncomplicated cellulitis.