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

NCT03637400 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 30284
• Study Type: interventional
• Target: 269
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Methicillin-resistant Staphylococcus Aureus; Skin Infection

Outcome Measures

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.

  Day 2-3 (48-72 hours)

Secondary Outcomes (7)

• Clinical cure at the End of Treatment (EOT) visit

  Day 7

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

  Day 37

• Adverse events

  Day 0-365

• Adverse events that are treatment limiting

  Day 0-365

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

  Day 37

Study Arms (2)

Trimethoprim/sulfamethoxazole (TMP-SMX)

EXPERIMENTAL

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

Doxycycline (DOXY)

EXPERIMENTAL

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

TMP-SMX DRUG

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

Also known as: Trimethoprim/sulfamethoxazole

Trimethoprim/sulfamethoxazole (TMP-SMX)

DOXY DRUG

DOXY will be administered over a period of 7 days.

Also known as: Doxycycline

Doxycycline (DOXY)

Eligibility Criteria

• Age: 9 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 9 years to 85 years
• Able to complete the informed consent 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
• Willing and able to complete the study protocol, study-related activities, and visits
• 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:
• Erythema
• Swelling or induration
• Local warmth
• Purulent drainage
• Tenderness to palpation or pain
• Pus or drainage from wound that can be sent for clinical culture
• Able to take oral antibiotic therapy, either in pill or suspension form
• 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
• Patients who have received prior antibacterial therapy with anti-staphylococcal activity within the prior 14 days:
• 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.
• 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.

You may not qualify if:

• Cellulitis without abscess, drainage, or other culturable exudate.
• Hospital inpatient
• Hospitalization within the prior 14 days
• Residence in a long-term skilled nursing facility
• Requirement for hospitalization for skin infection or other condition
• Previous enrollment in this protocol
• Participation in another clinical trial within the previous 30 days
• Superficial skin infection only, including
• Impetigo
• Ecthyma
• Folliculitis
• Infections that have a high cure rate after surgical incision alone (such as isolated furunculosis) or after topical or local measures
• Unstable psychiatric or psychological condition rendering the subject unlikely to be cooperative or to complete study requirements
• 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
• Systolic blood pressure \> 180 mm Hg

Sponsors & Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Washington University School of Medicine: collaborator
• University of California, Los Angeles: collaborator

Study Sites (3)

Olive View-UCLA Medical Center

Sylmar, California, 91342, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90509, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Related Publications (10)

• Chambers HF. The changing epidemiology of Staphylococcus aureus? Emerg Infect Dis. 2001 Mar-Apr;7(2):178-82. doi: 10.3201/eid0702.010204.

  PMID: 11294701 BACKGROUND

• 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.

  PMID: 10589891 BACKGROUND

• 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.

  PMID: 9486753 BACKGROUND

• 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.

  PMID: 11699844 BACKGROUND

• 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.

  PMID: 12588006 BACKGROUND

• 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.

  PMID: 14561958 BACKGROUND

• 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.

  PMID: 12931079 BACKGROUND

• 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.

  PMID: 16791134 BACKGROUND

• 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.

  PMID: 9697748 BACKGROUND

• 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.

  PMID: 15472848 BACKGROUND

MeSH Terms

Conditions

Cellulitis

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; Doxycycline

Condition Hierarchy (Ancestors)

Skin Diseases, Infectious; Infections; Suppuration; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Loren G Miller, MD, MPH

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

  PRINCIPAL INVESTIGATOR

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

  Washington Univeristy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double blind trial in which both subjects and study personnel will be masked to the specific treatment arm to which the subject has been assigned and to the results of cultures obtained from the site of infection. The pharmacist will only be unblinded to the liquid formulation, in order to prepare the formulation based upon the subject's weight.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: August 20, 2018
• Study Start: November 26, 2018
• Primary Completion: February 12, 2024
• Study Completion: June 30, 2025
• Last Updated: December 4, 2025

Record last verified: 2025-11

Locations

US (3)