Doxycycline vs TMP-SMX for Skin Infections

(TODOS Trial)

No longer recruiting at 3 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two antibiotics, doxycycline and trimethoprim/sulfamethoxazole, in treating uncomplicated skin infections such as boils or pus-filled infections. The goal is to determine which antibiotic more effectively cures these infections. Individuals with pus-filled skin infections accompanied by redness, swelling, or pain lasting at least 24 hours may qualify for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that doxycycline is usually well-tolerated for treating bacterial infections. The FDA has approved it for skin and soft tissue infections, like those in this trial. Some side effects may include nausea and increased sensitivity to sunlight, but serious reactions are rare.

Studies indicate that trimethoprim-sulfamethoxazole (TMP-SMX) can cause skin reactions more often than some other antibiotics. These reactions can include rashes and, in rare cases, more severe issues like Stevens-Johnson syndrome, a serious skin disorder. Despite these risks, TMP-SMX is widely used and often effective for treating skin infections.

Both antibiotics have been used for many years and have known safety profiles, but potential side effects should be considered. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for skin infections, which often include antibiotics like clindamycin or cephalexin, Doxycycline and Trimethoprim-Sulfamethoxazole (TMP-SMX) offer unique benefits. Doxycycline is known for its anti-inflammatory properties, which can be particularly helpful in reducing swelling and redness associated with infections. TMP-SMX targets a broad spectrum of bacteria, making it a versatile option for various types of skin infections. Researchers are excited about these treatments because they offer potential alternatives with different mechanisms of action, which could be more effective or have fewer side effects than current options.

What evidence suggests that this trial's treatments could be effective for uncomplicated skin and soft tissue infections?

This trial will compare the effectiveness of Doxycycline and Trimethoprim-Sulfamethoxazole (TMP-SMX) in treating skin infections. A previous study found Doxycycline effective for skin and soft tissue infections (SSTIs), and the FDA has approved it for this use. Research has also shown that Doxycycline aids in wound healing, benefiting skin infections. Conversely, several studies on TMP-SMX have demonstrated its effectiveness for SSTIs, with 8 out of 10 trials confirming its efficacy. TMP-SMX also outperformed a placebo in improving skin infection outcomes. Both antibiotics have strong evidence supporting their use for skin infections, making them good options for treating these conditions. ^{4 6 7 8 9}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10756378/

Doxycycline Prophylaxis for Skin and Soft Tissue Infections ...

Our data indicate that doxycycline prophylaxis in this population was associated with a significantly decreased rate of hospitalization for SSTI, decreased rate ...

2.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK555888/

Doxycycline Hyclate - StatPearls - NCBI Bookshelf - NIH

According to the Infectious Diseases Society of America (IDSA), doxycycline is FDA-approved for the treatment of skin and soft tissue infections ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2949962323000013

Effect of combination antibiotic therapy on clinical failure ...

The predominant reason for clinical failure was worsening of infection followed by change in antibiotic and hospitalization.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03637400

Study Details | NCT03637400 | Short and Long Term ...

The purpose of this study is to compare how well two different antibiotics, doxycycline (DOXY) and trimethoprim/sulfamethoxazole (TMP/SMX), work at curing ...

5.

journals.cambridgemedia.com.au

journals.cambridgemedia.com.au/wpr/volume-32-number-3/influence-doxycycline-wound-healing-systematic-review-meta-analysis-and-grade-assessment-animal-experimental-trials

Influence of doxycycline on wound healing: a systematic ...

Doxycycline shows notable advantages in wound healing compared to placebos or other agents, but replicability in clinical settings is necessary.

6.

mayoclinic.org

mayoclinic.org/drugs-supplements/doxycycline-oral-route/description/drg-20068229

Doxycycline (oral route) - Side effects & dosage

Doxycycline is used to treat bacterial infections in many different parts of the body. It is also used to treat pimples and abscesses (usually on the face) ...

7.

drugs.com

drugs.com/doxycycline.html

Doxycycline: Uses, Dosage, Side Effects, Warnings

Doxycycline, a tetracycline antibiotic, is used to treat many different bacterial infections and skin conditions such as acne and rosacea.

8.

vionausa.com

vionausa.com/wp-content/uploads/2022/03/SDS-Doxycycline-Capsules.pdf

Safety Data Sheet DOXYCYCLINE HYCLATE CAPSULES ...

Doxycycline Hyclate is an antibacterial drug which is used to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ... If ...

9.

labeling.pfizer.com

labeling.pfizer.com/ShowLabeling.aspx?id=15256

VIBRAMYCIN®

PRECLINICAL SAFETY DATA. Long-term studies in animals to evaluate carcinogenic potential of doxycycline have not been conducted. However, there has been ...