Uncomplicated Skin and Soft Tissue Infections Caused by Community-Associated Methicillin-Resistant Staphylococcus Aureus

NCT00730028 | Completed Phase 2 Results

• 2 other identifiers: 07-0051UCSF CA-MRSA
• Study Type: interventional
• Target: 1,310
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this clinical trial is to evaluate 2 different antibiotics, drugs that fight bacteria, \[clindamycin (CLINDA) and trimethoprim-sulfamethoxazole (TMP-SMX)\] and wound care for the outpatient management of uncomplicated skin and soft tissue infections (uSSTIs) in children and adults. The study will occur in areas where community associated methicillin-resistant Staphylococcus (S.) aureus are common. S. aureus is a type of bacteria. A total of 1310 volunteers, greater than or equal to 6 months of age and adults 85 years or younger, non-immunocompromised, with uSSTIs (in particular abscess and/or cellulitis) will be enrolled in this study. Subjects will be treated with one of the following: CLINDA, TMP-SMX, or placebo (contains no medication). Volunteers will be grouped based on the presence of cellulitis or abscess, whether the abscess can be surgically drained, and its size. The subject participation duration for this study is about 6 weeks.

Conditions

Staphylococcal Infection

Keywords

Methicillin-resistant Staphylococcus aureus (MRSA), cellulitis, abscess, children, elderly

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Achieving Clinical Cure, Defined as Absence of Clinical Failure, in the Evaluable Population.

  Clinical failure is defined as the occurence of any of the following: 1. Lack of resolution at the Test of Cure (TOC) visit in any or all of the following: erythema, tenderness, purulent drainage, swelling, and local warmth. Erythema or tenderness that was considered due the surgical therapy itself (incision and drainage), was not considered to be indicative of clinical failure. 2. Occurrence of a SSTI at another site other than the site(s) under study. 3. Intolerance of study medication or a treatment-limiting adverse reaction necessitating discontinuation of study drug within the first 48 hours. 4. Administration of other antimicrobial therapy for treatment of a SSTI at any time through the TOC visit. 5. Unplanned surgical procedure for the infection under study at any time through the TOC visit. 6. Hospitalization for treatment of active or invasive infection at any time through the TOC visit.

  Test of cure (TOC) (7-10 days after completion of therapy)

• Percentage of Participants Achieving Clinical Cure, Defined as Absence of Clinical Failure, in the Intent-to-Treat (ITT) Population.

  Clinical failure is defined as the occurence of any of the following: 1. Lack of resolution at the Test of Cure (TOC) visit in any or all of the following: erythema, tenderness, purulent drainage, swelling, and local warmth. Erythema or tenderness that was considered due the surgical therapy itself (incision and drainage), was not considered to be indicative of clinical failure. 2. Occurrence of a SSTI at another site other than the site(s) under study. 3. Intolerance of study medication or a treatment-limiting adverse reaction necessitating discontinuation of study drug within the first 48 hours. 4. Administration of other antimicrobial therapy for treatment of a SSTI at any time through the TOC visit. 5. Unplanned surgical procedure for the infection under study at any time through the TOC visit. 6. Hospitalization for treatment of active or invasive infection at any time through the TOC visit.

  Test of cure (TOC) (7-10 days after completion of therapy)

Secondary Outcomes (6)

• Number of Participants Reporting Adverse Events.

  End of Treatment (EOT) (48 hours after completion of therapy); Test of Cure (TOC) (7-10 days after completion of therapy); One Month Follow-up Visit (OMFU)

• Number of Participants Reporting Adverse Events That Are Treatment Limiting.

  End of Treatment (EOT) (48 hours after completion of therapy); Test of Cure (TOC) (7-10 days after completion of therapy); One Month Follow-up Visit (OMFU)

• Percentage of Participants Achieving Clinical Cure at the End of Treatment (EOT) Visit for the Evaluable Population.

  EOT visit within 48 hours of completion of therapy

• Percentage of Participants Achieving Clinical Cure at the End of Treatment (EOT) Visit for the Intent-to-Treat (ITT) Population.

  EOT visit within 48 hours of completion of therapy

• Percentage of Participants Achieving Clinical Cure at the One Month Follow-up (OMFU) Visit for the Evaluable Population.

  OMFU visit

Study Arms (2)

Limited Abscess

EXPERIMENTAL

Limited abscess with or without cellulitis less than or equal to 5 cm in diameter will be randomized to receive a 10-day course a) TMP-SMX 160/800 mg twice daily for adults; 8-10 mg/kg of TMP, 40-50 mg/kg of SMX twice daily for children; or b) CLINDA 300 mg three times daily for adults; 25-30 mg/kg/day divided three times daily for children; or c) placebo two capsules three times daily.

Drug: Trimethoprim-sulfamethoxazole; Other: Placebo; Drug: Clindamycin

Cellulitis or Larger Abscess

EXPERIMENTAL

Subjects with cellulitis only or abscess \> 5 cm in diameter, or with 2 or more sites of skin infection will be randomized to receive a 10-day course a) TMP-SMX 160/800 mg twice daily for adults; 8-10 mg/kg of TMP, 40-50 mg/kg of SMX twice daily for children; or b) CLINDA300 mg three times daily for adults; 25-30 mg/kg/day divided three times daily for children.

Drug: Trimethoprim-sulfamethoxazole; Drug: Clindamycin

Interventions

Trimethoprim-sulfamethoxazole DRUG

Trimethoprim-sulfamethoxazole (TMP-SMX) will be administered orally at a dose of 160 mg TMP and 800 mg SMX (as 2 single strength over encapsulated tablets) twice daily (adult or child \> 40 kg dose) or 8-10 mg TMP, 40-50 mg SMX per kg daily, divided into 2 daily doses (child \< 40 kg dose). Study drug will be administered for 10 days.

Cellulitis or Larger Abscess; Limited Abscess

Placebo OTHER

Placebo capsules will be identical in appearance to the CLINDA and TMP-SMX. Administered 3 times daily for 10 days.

Limited Abscess

Clindamycin DRUG

CLINDA (adult dose of 300 mg three times daily; pediatric dose of 25-30 mg/kg/day divided three times daily up to a maximum dose of 900 mg/day). Study drug will be administered for 10 days.

Cellulitis or Larger Abscess; Limited Abscess

Eligibility Criteria

• Age: 6 Months - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 6 months 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 7 and older.
• Willing and able to complete the study protocol, study-related activities, and visits.
• Diagnosis of uncomplicated skin and soft tissue infection (uSSTI), either 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
• Able to take oral antibiotic therapy, either in pill or suspension form.

You may not qualify if:

• Hospital in-patient.
• 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.
• Systolic blood pressure (SBP) less than an age-specific critical value:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (6)

San Francisco General Hospital - Infectious Diseases

San Francisco, California, 94110-3518, United States

Location

Harbor UCLA Medical Center - Medicine - Infectious Diseases

Torrance, California, 90502-2006, United States

Location

Morehouse School of Medicine - Morehouse Medical Associates - Atlanta

Atlanta, Georgia, 30303-2544, United States

Location

The University of Chicago - Comer Children's Hospital - Infectious Diseases

Chicago, Illinois, 60637-1425, United States

Location

Washington University School of Medicine in St. Louis - Infectious Diseases

St Louis, Missouri, 63110-1010, United States

Location

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, 37232-2573, United States

Location

Related Publications (2)

• Miller LG, Daum RS, Creech CB, Young D, Downing MD, Eells SJ, Pettibone S, Hoagland RJ, Chambers HF; DMID 07-0051 Team. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015 Mar 19;372(12):1093-103. doi: 10.1056/NEJMoa1403789.

  PMID: 25785967 RESULT

• Daum RS, Miller LG, Immergluck L, Fritz S, Creech CB, Young D, Kumar N, Downing M, Pettibone S, Hoagland R, Eells SJ, Boyle MG, Parker TC, Chambers HF; DMID 07-0051 Team. A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. N Engl J Med. 2017 Jun 29;376(26):2545-2555. doi: 10.1056/NEJMoa1607033.

  PMID: 28657870 DERIVED

MeSH Terms

Conditions

Staphylococcal Infections; Cellulitis; Abscess

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; Clindamycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Infectious; 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; Lincomycin; Lincosamides; Pyrrolidines; Glycosides; Carbohydrates

Results Point of Contact

• Title: Henry F. Chambers, MD
• Organization: San Francisco General Hospital, UCSF

hchambers@medsfgh.ucsf.edu

(415) 206 - 5437

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2008
• First Posted: August 8, 2008
• Study Start: April 1, 2009
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: March 17, 2016
• Results First Posted: March 17, 2016

Record last verified: 2015-04

Locations

US (6)