ClinicalTrials.gg
Sign In
CompletedNCT03637400TODOSUpdated Dec 4, 2025

Short and Long Term Outcomes of Doxycycline Versus Trimethoprim-Sulfamethoxazole for Skin and Soft Tissue Infections Treatment

A Phase 2 interventional study of TMP-SMX and DOXY in Methicillin-resistant Staphylococcus Aureus and Skin Infection, sponsored by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center. Completed at 3 sites in United States. Open to participants aged 9 Years to 85 Years. Per ClinicalTrials.gov, last updated 2025-12-04.

Sponsored by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Primary completion was Feb 2024, 2 years 8 months ago, and no results have been posted to the registry.
Phase
Phase 2
Study type
Interventional
Enrollment
269
Allocation
Randomized
Ages
9 Years to 85 Years
Sex
All
01

Study summary

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.

Read the detailed description

This is a phase IIb multicenter, randomized, double-blind trial in which enrolled subjects with abscess or cellulitis will be treated with either DOXY or TMP-SMX.

The overall objective is to provide a clinically relevant treatment strategy for uSSTI in children and adults in areas where CA-MRSA is prevalent. Out-patient subjects, both children and adults with abscess and/or purulent cellulitis will be enrolled into a randomized, double-blind trial in which enrolled subjects will be treated with either DOXY or TMP-SMX.

Background: Staphylococcus aureus is the most commonly identified cause of skin infections. In the last 15 years, there also has been an large increase in Staphylococcus aureus skin infection attributable to CA-MRSA (Methicillin-resistant Staphylococcus aureus) throughout the United States. However, optimal treatment remains unclear and several commonly used antibiotics such as doxycycline are commonly used but understudied. As resistance among CA-MRSA strains to commonly used antibiotics such as clindamycin continues to increase, there is a need to understand the relative safety and efficacy of alternative treatments, such as doxycycline. This clinical trial will evaluate DOXY and TMP-SMX for the outpatient management of uSSTI in two metropolitan areas, Los Angeles and St. Louis, cities with high prevalence of CA-MRSA. This trial will test important unanswered hypotheses relating to the treatment of CA-MRSA uSSTI and it will advance healthcare providers' ability to successfully manage adults and children with uSSTIs in areas where CA-MRSA is prevalent.

Methods: Out-patient subjects, both children and adults with abscess and/or purulent cellulitis will be enrolled into a randomized, double-blind trial in which enrolled subjects will be treated with either DOXY or TMP-SMX. Using a 1:1 randomized controlled trial of 462 subjects, the investigators aim to 1) compare the cure rate of DOXY to that of TMP-SMX for the treatment of patients throughout the study 2) compare rates of adverse events and of adverse events that are treatment limiting between DOXY and TMP-SMX 3) estimate relapse and recurrence of uSSTI among patients treated with DOXY and of TMP-SMX 4) estimate treatment failure among patients with uSSTI colonized with S. aureus at the anterior nares and oropharynx.

02

Conditions studied

  • Methicillin-resistant Staphylococcus Aureus
  • Skin Infection

Browse trials for

03

In context

Cellulitis

160 studies on the registry are indexed under Cellulitis; 14 are open to participants now.

This study's enrollment of 269 is above the median of 157 across 124 interventional studies indexed under Cellulitis.

Browse Cellulitis studies →

Lead sponsor

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center is the lead sponsor of 67 studies on the registry; 1 is open to participants now.

Of its 11 completed or terminated interventional studies of FDA-regulated products, 5 (45%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
9 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Age 9 years to 85 years
  2. Able to complete the process or, if a minor, a parent or guardian who is able to complete the informed consent process; an assent form also will be completed for children age 9 and older
  3. Willing and able to complete the study protocol, study-related activities, and visits

  4. Diagnosis of uSSTI, either purulent cellulitis (defined as an inflammation of skin and associated skin structures) or abscess (defined as a circumscribed collection of pus), evidenced by at least 2 of the following localized signs or symptoms on the skin for at least 24 hours:

    1. Erythema
    2. Swelling or induration
    3. Local warmth
    4. Purulent drainage
    5. Tenderness to palpation or pain
  5. Pus or drainage from wound that can be sent for clinical culture
  6. Able to take oral antibiotic therapy, either in pill or suspension form

  7. For women of , the participant agrees to use for the 7 days on the study medication and 7 days after completion of study medication

    Patients who have received prior antibacterial therapy with anti-staphylococcal activity within the prior 14 days:

  8. Received prior systemic antibacterial therapy with anti-staphylococcal activity for a skin infection and are not on it currently, and have relapse/recurrence of skin infection.
  9. Received prior systemic antibacterial therapy with anti-staphylococcal activity for a skin infection (including those currently on it) without adequate source control of their skin infection and lack of response (i.e., persistence or progression of the lesion) to pre-study antibacterial therapy with on-going evidence of skin infection.
  10. Received prior antibiotics with anti-staphylococcal activity for non-skin infections and who developed a skin infection while on these antibiotics or shortly after completing these antibiotics.

Exclusion criteria

Exclusion Criteria:

  1. Cellulitis without abscess, drainage, or other culturable exudate.
  2. Hospital inpatient
  3. Hospitalization within the prior 14 days
  4. Residence in a long-term skilled nursing facility
  5. Requirement for hospitalization for skin infection or other condition
  6. Previous enrollment in this protocol
  7. Participation in another clinical trial within the previous 30 days

  8. Superficial skin infection only, including

    1. Impetigo
    2. Ecthyma
    3. Folliculitis
    4. Infections that have a high cure rate after surgical incision alone (such as isolated furunculosis) or after topical or local measures
  9. Unstable psychiatric or psychological condition rendering the subject unlikely to be cooperative or to complete study requirements
  10. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with the adherence or subject compliance with study requirements
  11. Systolic blood pressure > 180 mm Hg

  12. Systolic blood pressure (SBP) less than an age-specific critical value:

    1. Age 9 to 17 years: \< 90 mm Hg
    2. Age ≥ 18 years: \< 90 mm Hg
  13. Heart rate less than 45 beats per minute (BPM)

  14. Heart rate greater than an age-specific-critical value:

    1. Age 9 to 17 years: > 120 BPM
    2. Age ≥ 18 years: > 120 BPM
  15. Oral temperature (or equivalent rectal, tympanic membrane, axillary defined in Table 2) less than 35.5° C (95.9° F)

  16. Oral temperature (or equivalent rectal, tympanic membrane, axillary defined in Table 2) greater than age-specific critical value:

    1. Age 9 to 17 years: > 38.5° C (101.3° F)
    2. Age ≥ 18 years: > 38.5° C (101.3° F)
  17. Documented human or witnessed animal bite in the past 30 days at the site of infection
  18. Received prior systemic antibacterial therapy with anti-staphylococcal activity within the prior 14 days who do not meet inclusion criteria 8, 9 and 10.
  19. The following concomitant medications: warfarin, phenytoin, methotrexate, dofetilide, methanamine, amiodarone, leucovorin, pyrimethamine, acitretin, atovaquone, atovaquone/proguanil, isotretinoin, or sulfonylureas and systemically administered antibacterial agents with activity against staphylococci
  20. Diagnosed or suspected disseminated or severe S. aureus or GAS infection, including lymphangitic spread of skin infection, septicemia, bacteremia, pneumonia, endocarditis, osteomyelitis, septic arthritis, gangrene, necrotizing fasciitis, myositis, or other serious or infections

  21. Infection at an anatomical site skin requiring specialized management or specialized antimicrobial therapy, including

    1. Periauricular or orbital infection
    2. Perirectal infection
    3. Suspected deep space infection of the hand or foot
    4. Genital infection
    5. Mastitis
    6. Bursitis
  22. Radiographic evidence or suspicion of gas in the tissue or foreign body infection (note: radiography is not required for screening and can be performed at the discretion of the treating physician)
  23. Gastrointestinal symptoms such as nausea, vomiting, or diarrhea of a severity that would preclude consumption of oral antibiotics
  24. or history of allergic reaction to study drug
  25. History of G6PD deficiency
  26. Pregnant or lactating, or intending to become pregnant within 3 months after screening Women of must have a negative urine or serum pregnancy test result within 1 day prior to initiation of study drug.
  27. Severe or morbid obesity with a (BMI) >45 kg/m2; patients above BMI >45 can be enrolled if their weight is \< 100 kg kg/m2.

  28. Complicated skin or soft tissue infection, such as

    1. Catheter or catheter site infection within 30 days of placement
    2. Surgical site infection
    3. Known or suspected prosthetic device infection
    4. Suspected Gram-negative or anaerobic pathogen
    5. Unusual exposure history (e.g., underwater injury, fish-tank exposure, heavy soil exposure, etc)
  29. History of drug-induced thrombocytopenia and documented megaloblastic anemia due to folate deficiency.
  30. Infection at the site of an area of underlying skin disease such as chronic eczema, psoriasis, atopic dermatitis, or chronic venous stasis

  31. History of severe underlying immunocompromising condition or immunodeficiency, for example

    1. Chronic renal failure, \<30 ml/min
    2. Renal dialysis within the past 180 days
    3. -positive with either \<200 or \<4% CD4 in the past 180 days or HIV-positive and no documented CD4 count in the past 4 months
    4. Cancer or with receipt of systemic chemotherapy in the prior 180 days
    5. Organ or bone marrow transplantation (ever), therapy within the past 180 days, severe liver disease
    6. Other serious underlying disease, as determined by the treating physician or the investigator
Terms in these criteria, in plain language(10)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

CD4 count

The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
269 participants (actual)

Study arms

  • Experimental
    Trimethoprim/sulfamethoxazole (TMP-SMX)

    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.

    Drug: TMP-SMX

  • Experimental
    Doxycycline (DOXY)

    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.

    Drug: DOXY

Interventions

  • DrugTMP-SMX

    TMP-SMX will be administered over a period of 7 days.

    Also known as: Trimethoprim/sulfamethoxazole

  • DrugDOXY

    DOXY will be administered over a period of 7 days.

    Also known as: Doxycycline

06

What researchers measure

Primary outcomes

  1. Clinical cure at Early Clinical Response (ECR) visit

    Clinical cure is the absence of clinical failure which is defined as occurrence of any one of the following events at ECR: * Fever (one or more temperature readings of ≥37.7°C between 48 and 72 hours); * Spread of lesion defined as an increase in size (length, width, or area) of the redness, edema, and/or induration such that the size of the lesion is greater than the size at baseline; * Administration of rescue antibacterial drug therapy or any non-trial antibacterial drug therapy for the treatment of SSTI prior to the ECR evaluation; * Requires an additional unplanned surgical procedure after start of therapy; * Death.

    Time frame: Day 2-3 (48-72 hours)

Secondary outcomes

  1. Clinical cure at the End of Treatment (EOT) visit

    Clinical cure will be defined as complete or nearly complete resolution of baseline signs and symptoms of the primary infection such that no further treatment with antibiotics is needed

    Time frame: Day 7

  2. Clinical cure at the One Month Follow-up (OMFU) visit

    Clinical cure will be defined as complete or nearly complete resolution of baseline signs and symptoms of the primary infection such that no further treatment with antibiotics is needed

    Time frame: Day 37

  3. Adverse events

    An adverse event (AE) is defined as any unfavorable or undesirable effect (sign, symptom, laboratory abnormality, or condition), regardless of causal relationship to study procedures or participation that occurs in a subject while enrolled in this clinical trial. Any medical condition that is present at the time that the subject is screened should be considered as baseline and not reported as an AE. However, if it deteriorates at any time during the study, it should be recorded as an AE. The occurrence of an AE may come to the attention of study personnel during study visits and interviews of a study recipient presenting for medical care, or upon review by a study monitor.

    Time frame: Day 0-365

  4. Adverse events that are treatment limiting

    An adverse event (AE) is defined as any unfavorable or undesirable effect (sign, symptom, laboratory abnormality, or condition), regardless of causal relationship to study procedures or participation that occurs in a subject while enrolled in this clinical trial. Any medical condition that is present at the time that the subject is screened should be considered as baseline and not reported as an AE. However, if it deteriorates at any time during the study, it should be recorded as an AE. The occurrence of an AE may come to the attention of study personnel during study visits and interviews of a study recipient presenting for medical care, or upon review by a study monitor.

    Time frame: Day 0-365

  5. Relapse/recurrent SSTI at One Month Follow-Up (OMFU)

    Relapse will be defined as a return of the original infection after initial improvement prior to or at the OMFU visit. Recurrence will be defined as a return of skin infection at the original site, even if considered to be a separate occurrence, after the OMFU visit or a skin infection at a new site of infection.

    Time frame: Day 37

  6. Relapse/recurrent SSTI at 6 Month Follow-Up (6MFU)

    Relapse will be defined as a return of the original infection after initial improvement prior to or at the 6MFU visit. Recurrence will be defined as a return of skin infection at the original site, even if considered to be a separate occurrence, after the 6MFU visit or a skin infection at a new site of infection.

    Time frame: Day 180

  7. Relapse/recurrent SSTI at 12 Month Follow-Up (12MFU)

    Relapse will be defined as a return of the original infection after initial improvement prior to or at the 12MFU visit. Recurrence will be defined as a return of skin infection at the original site, even if considered to be a separate occurrence, after the 12MFU visit or a skin infection at a new site of infection.

    Time frame: Day 365

07

Study locations

3 sites
  • Olive View-UCLA Medical Center
    Sylmar, California 91342, United States
  • Harbor-UCLA Medical Center
    Torrance, California 90509, United States
  • Washington University
    St Louis, Missouri 63130, United States
08

References and documents

Publications

  • Chambers HF. The changing epidemiology of Staphylococcus aureus? Emerg Infect Dis. 2001 Mar-Apr;7(2):178-82. doi: 10.3201/eid0702.010204. PubMed 11294701 ↗
  • Gorak EJ, Yamada SM, Brown JD. Community-acquired methicillin-resistant Staphylococcus aureus in hospitalized adults and children without known risk factors. Clin Infect Dis. 1999 Oct;29(4):797-800. doi: 10.1086/520437. PubMed 10589891 ↗
  • Herold BC, Immergluck LC, Maranan MC, Lauderdale DS, Gaskin RE, Boyle-Vavra S, Leitch CD, Daum RS. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA. 1998 Feb 25;279(8):593-8. doi: 10.1001/jama.279.8.593. PubMed 9486753 ↗
  • Centers for Disease Control and Prevention (CDC). Methicillin-resistant Staphylococcus aureus skin or soft tissue infections in a state prison--Mississippi, 2000. MMWR Morb Mortal Wkly Rep. 2001 Oct 26;50(42):919-22. PubMed 11699844 ↗
  • Centers for Disease Control and Prevention (CDC). Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections--Los Angeles County, California, 2002-2003. MMWR Morb Mortal Wkly Rep. 2003 Feb 7;52(5):88. PubMed 12588006 ↗
  • Centers for Disease Control and Prevention (CDC). Methicillin-resistant Staphylococcus aureus infections in correctional facilities---Georgia, California, and Texas, 2001-2003. MMWR Morb Mortal Wkly Rep. 2003 Oct 17;52(41):992-6. PubMed 14561958 ↗
  • Centers for Disease Control and Prevention (CDC). Methicillin-resistant staphylococcus aureus infections among competitive sports participants--Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000-2003. MMWR Morb Mortal Wkly Rep. 2003 Aug 22;52(33):793-5. PubMed 12931079 ↗
  • Centers for Disease Control and Prevention (CDC). Methicillin-resistant Staphylococcus aureus skin infections among tattoo recipients--Ohio, Kentucky, and Vermont, 2004-2005. MMWR Morb Mortal Wkly Rep. 2006 Jun 23;55(24):677-9. PubMed 16791134 ↗
  • Adcock PM, Pastor P, Medley F, Patterson JE, Murphy TV. Methicillin-resistant Staphylococcus aureus in two child care centers. J Infect Dis. 1998 Aug;178(2):577-80. doi: 10.1086/517478. PubMed 9697748 ↗
  • Ellis MW, Hospenthal DR, Dooley DP, Gray PJ, Murray CK. Natural history of community-acquired methicillin-resistant Staphylococcus aureus colonization and infection in soldiers. Clin Infect Dis. 2004 Oct 1;39(7):971-9. doi: 10.1086/423965. Epub 2004 Sep 2. PubMed 15472848 ↗

Individual participant data

Plan to share: Undecided

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 4, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03637400
Lead sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Washington University School of Medicine, University of California, Los Angeles
Responsible party
loren g miller (Principal Investigator, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center) — Principal investigator
First posted
Aug 20, 2018
Start date
Nov 26, 2018
Primary completion
Feb 12, 2024
Completion
Jun 30, 2025
Last update
Dec 4, 2025

Study contacts

Loren G Miller, MD, MPH
principal investigator · The Lundquist Institute For Biomedical Innovation at Harbor-UCLA Medical Center
Fritz Stephanie, MD, MSCI, FAAP, FIDSA, FPIDS
principal investigator · Washington Univeristy

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Doxycycline

Other studies in this condition

Cellulitis →

Other studies from this sponsor

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Start the discussion