Doxycycline vs TMP-SMX for Skin Infections

(TODOS Trial)

Recruiting at 2 trial locations

Overseen By Donna Phan Tran, MPH

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Must not be taking: Warfarin, Phenytoin, Methotrexate, others

Disqualifiers: Hospitalization, Psychiatric condition, Hypertension, 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

Compensation: Varies

Number of Visits: 1

Duration: 1 week

462 Participants Needed

Trial Summary

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 taking certain medications like warfarin, phenytoin, or methotrexate, among others. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug Doxycycline for skin infections?

A study found that doxycycline was effective for treating skin and soft tissue infections, with a clinical failure rate of 9% in the trimethoprim-sulfamethoxazole group, but no significant difference in failure rates between the two drugs. Doxycycline is also widely used for other bacterial infections, which supports its effectiveness. ^{1 2 3 4 5}

Is Doxycycline or TMP-SMX generally safe for treating skin infections?

Doxycycline is known for its excellent safety profile and is widely used for various infections. However, Trimethoprim-Sulfamethoxazole (TMP-SMX) can have adverse effects, especially in people with kidney or heart issues, and may cause serious side effects like hyperkalemia (high potassium levels in the blood). ^{1 2 3 4 6}

How does the drug Doxycycline differ from other treatments for skin infections?

Doxycycline is unique for its intracellular mechanism of action, excellent safety profile, and low cost, making it a widely used antibiotic for various infections, including skin infections. Unlike TMP-SMX, which has a higher clinical failure rate in some cases, doxycycline is effective against methicillin-resistant Staphylococcus aureus (MRSA) and is often used when other options are limited. ^{1 3 4 7 8}

What is the purpose of this trial?

The purpose of this study is to compare how well two different antibiotics, doxycycline (DOXY) and trimethoprim/sulfamethoxazole (TMP/SMX), work at curing uncomplicated skin and soft tissue infection (uSSTI) such as 1.Boils (pus in the skin, also known as abscesses and furuncles) or 2. Infections that appear only on the skin surface (called cellulitis and erysipelas) that have pus.

Research Team

Loren G Miller

Principal Investigator

The Lundquist Institute For Biomedical Innovation at Harbor-UCLA Medical Center

Fritz Stephanie, MD, MSCI, FAAP, FIDSA, FPIDS

Principal Investigator

Washington Univeristy

Eligibility Criteria

This trial is for people aged 9 to 85 with uncomplicated skin and soft tissue infections like boils or cellulitis. Participants must be able to take oral antibiotics, follow the study plan, and not have been hospitalized recently. Women who can get pregnant should use birth control during and after the study. Those with severe health issues or on certain medications cannot join.

Inclusion Criteria

For women of childbearing potential, the participant agrees to use birth control for the 7 days on the study medication and 7 days after completion of study medication

I had staph antibiotics recently due to a skin infection that either came back or didn't fully heal.

I am between 9 and 85 years old.

Exclusion Criteria

Heart rate less than 45 beats per minute (BPM)

I have not been hospitalized in the last 2 weeks.

Oral temperature (or equivalent rectal, tympanic membrane, axillary defined in Table 2) less than 35.5° C (95.9° F)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are treated with either doxycycline or trimethoprim-sulfamethoxazole for uncomplicated skin and soft tissue infections

1 week

Daily administration

Follow-up

Participants are monitored for clinical cure and adverse events

12 months

Visits at 1 month, 6 months, and 12 months

Treatment Details

Interventions

• Doxycycline
• Trimethoprim-Sulfamethoxazole

Trial Overview The trial compares two antibiotics: doxycycline (DOXY) and trimethoprim-sulfamethoxazole (TMP/SMX), to see which one better treats simple skin infections that show signs like redness, swelling, warmth, pus drainage, or pain.

Participant Groups

Group I: Trimethoprim/sulfamethoxazole (TMP-SMX) Experimental Treatment 1 Intervention

TMP-SMX will be dosed as follows: for adults, 160/800 mg administered as two single strength (SS) over-encapsulated tablets (equivalent to one double strength (DS) tablet) twice daily. As dosages of these medications may be lower in children with lower body weight (\<40 kg), we will use weight based liquid medications for children \< 40 kg (TMP/SMX dosed based on 8-10 mg/kg of TMP daily, divided into two daily doses) for those children who are under 40 kg in weight. As dosages of these medications are higher in persons with high body weight (\>100 kg), we will use TMP/SMX 160/800 mg administered as four single strength (SS) over-encapsulated tablets (equivalent to two double strength (DS) tablet) twice daily.

Group II: Doxycycline (DOXY) Experimental Treatment 1 Intervention

DOXY will be dosed as follows: for adults, two 50 mg tabs (100 mg total) given twice daily. As dosages of these medications may be lower in children with lower body weight (\<40 kg), we will use weight based liquid medications for children \< 40 kg (DOXY 2.2 mg/kg twice daily) for those children who are under 40 kg in weight. The doxycycline dose will remain the same for persons with high body weight (\>100 kg) and four additional placebo tabs will be given to subjects \> 100 kg randomized to doxycycline.

Doxycycline is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in European Union as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in Canada as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in Japan as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Who Is Running the Clinical Trial?

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Lead Sponsor

Trials

105

Recruited

46,600+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Findings from Research

Doxycycline is a widely used antibiotic with a strong safety profile and low cost, effective against community-acquired pneumonia, atypical pneumonia, and sexually transmitted diseases, making it increasingly important as new applications are discovered.

Minocycline, similar to doxycycline, offers excellent tissue penetration for treating difficult infections like MRSA, while TMP-SMX is effective for urinary and respiratory infections and is gaining importance in treating infections related to AIDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New uses for older antibiotics. The 'rediscovery' of four beneficial and cost-effective antimicrobials. Cunha, BA.[2019]

In a study of 6162 outpatients, those receiving high-dose trimethoprim-sulfamethoxazole (TMP-SMX) had a significantly higher incidence of hyperkalemia (3.06% vs 1.05%) and acute renal injury (1.99% vs 0.70%) compared to those on low-dose TMP-SMX.

Key risk factors for hyperkalemia and acute renal injury included older age, use of NSAIDs or ACE inhibitors, and elevated baseline serum creatinine, highlighting the need for careful monitoring of potassium and kidney function in patients prescribed high-dose TMP-SMX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications. Gentry, CA., Nguyen, AT.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

New uses for older antibiotics. The 'rediscovery' of four beneficial and cost-effective antimicrobials. [2019]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

A comparison of adverse drug reactions between high- and standard-dose trimethoprim-sulfamethoxazole in the ambulatory setting. [2022]

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

The Risks of Using Trimethoprim/Sulfamethoxazole in Patients with Renal and Cardiac Compromise. [2022]

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

Prospective randomized trial of empiric therapy with trimethoprim-sulfamethoxazole or doxycycline for outpatient skin and soft tissue infections in an area of high prevalence of methicillin-resistant Staphylococcus aureus. [2018]

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

Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. [2019]

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

An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications. [2015]

7. Poland pubmed.ncbi.nlm.nih.gov

The use of trimethoprim and sulfamethoxazole (TMP-SMX) in dermatology. [2016]

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

Use of oral tetracyclines in the treatment of adult outpatients with skin and skin structure infections: Focus on doxycycline, minocycline, and omadacycline. [2022]