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| Sponsor: | National Institute of Allergy and Infectious Diseases (NIAID) |
|---|---|
| Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00730028 |
Purpose
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, 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Methicillin-Resistant S.Aureus |
Drug: Clindamycin Drug: Placebo Drug: Trimethoprim-sulfamethoxazole (TS) |
Phase II Phase III |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
| Official Title: | Randomized, Double-Blind Trial of Clindamycin, Trimethoprim-Sulfamethoxazole, or Placebo for Uncomplicated Skin and Soft Tissue Infections Caused by Community-Associated Methicillin-Resistant Staphylococcus Aureus |
| Estimated Enrollment: | 1310 |
| Study Start Date: | April 2009 |
| Estimated Study Completion Date: | July 2011 |
| Estimated Primary Completion Date: | July 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Limited Abscess: Experimental
Limited abscess (i.e., less than or equal to 5 cm in diameter (or proportionately smaller in size in children depending on age) will be randomized to receive a) TMP-SMX or b) CLINDA or c) placebo.
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Drug: Clindamycin
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.
Drug: Placebo
Placebo capsules will be identical in appearance to the CLINDA and TMP-SMX. Administered for 10 days.
Drug: Trimethoprim-sulfamethoxazole (TS)
Trimethoprim-sulfamethoxazole (TMP-SMX) will be administered orally at a dose of 160 mg TMP and 800 mg SMX (as 2 single strength overencapsulated 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.
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Cellulitis or Larger Abscess: Experimental
Subjects with cellulitis or abscess greater than 5 cm in diameter (or proportionately smaller size in children depending on age), or with 2 or more sites of skin infection will be randomized to receive a) TMP-SMX or b) CLINDA.
|
Drug: Clindamycin
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.
Drug: Trimethoprim-sulfamethoxazole (TS)
Trimethoprim-sulfamethoxazole (TMP-SMX) will be administered orally at a dose of 160 mg TMP and 800 mg SMX (as 2 single strength overencapsulated 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.
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Clinical practice in the treatment of community-onset skin and soft tissue infections (SSTI) has not kept pace with the emergence of methicillin-resistant Staphylococcus aureus (MRSA) in the community. This clinical trial will evaluate clindamycin (CLINDA) and trimethoprim-sulfamethoxazole (TMP-SMX) and wound care for the outpatient management of uncomplicated skin and soft tissue infection (uSSTI) in 3 metropolitan areas, Chicago, Los Angeles, and San Francisco, cities with high prevalence of community acquired (CA)-MRSA. This is a phase IIb multicenter, stratified, randomized, double-blind trial in which enrolled subjects with abscess or cellulitis will be treated with CLINDA, TMP-SMX, or placebo. Participants will include 1310 non-immunocompromised out-patients age 6 months to 85 years with SSTIs not requiring hospital admission. Subjects will undergo a screening/baseline evaluation, including determination of presence and size of abscess and/or presence of cellulitis. Subjects will then be randomized to receive treatment with either CLINDA, TMP-SMX, or placebo depending on whether they have: a larger drainable abscess, defined as greater than 5 cm in diameter in adults and as greater than 3 cm in diameter for ages 6-11 months, greater than 4 cm for ages 1-8 years, and greater than 5 cm for age 9 years and older; a limited drainable abscess, defined as less than or equal to 5 cm for adults and as less than or equal to 3 cm for ages 6-11 months, less than or equal to 4 cm for ages 1-8 years, and less than or equal to 5 cm for age 9 years and older; or cellulitis or erysipelas only. If the diameter of the abscess greater than 5 cm (smaller for children depending on age) or 2 or more sites of skin infection are present the subject will be randomized (1:1) to 10 days of therapy with TMP-SMX or CLINDA. If the diameter of the abscess less than or equal to 5 cm (smaller for children depending on age) then the subject will be randomized (1:1:1) to TMP-SMX, CLINDA or placebo for 10 days. Subjects with cellulitis or erysipelas only will be randomized (1:1) to TMP-SMX or CLINDA for 10 days. Subjects will be provided study drug, instructed in its use, and scheduled for 4 follow-up visits including: wound check (24-48 hours after enrollment); end of therapy (48 hours after completion of therapy); test of cure (7-10 days after completion of therapy); and a final visit at one month after completion of therapy. The primary objectives of this study are: to compare the cure rate of CLINDA to that of TMP-SMX for the treatment of patients with cellulitis or larger abscess at the Test of Cure (TOC) visit and to compare the cure rate of CLINDA, TMP-SMX, and placebo, each in conjunction with surgical drainage for the treatment of subjects with limited abscess at the TOC visit. The primary efficacy endpoint for the trial is clinical cure, which is the absence of clinical failure. The secondary objectives are: to estimate the cure rates of CLINDA and of TMP-SMX, and their difference, for limited abscess, cellulitis, or larger abscess: at the End of Treatment (EOT) visit, one month follow-up (OMFU) visit, in children and adults at the TOC visit; and for children versus adults at the TOC visit; to compare rates of adverse events and of adverse events that are treatment limiting between CLINDA and TMP-SMX for limited abscess, cellulitis, or larger abscess: at the TOC visit, EOT visit, and for children and adults separately at the TOC visit; and to estimate rates of adverse events and of adverse events that are treatment limiting for CLINDA and for TMP-SMX for limited abscess, cellulitis, or larger abscess for children, for adults, and the difference between children and adults. Secondary efficacy endpoints are: clinical cure at the EOT visit and clinical cure at the OMFU visit. Study duration will be for 3 years with subject participation duration equal to 6 weeks.
Eligibility| Ages Eligible for Study: | 6 Months to 85 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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:
Exclusion Criteria:
Superficial skin infection only, including:
Systolic blood pressure (SBP) less than an age-specific critical value:
Heart rate greater than an age-specific critical value:
Oral temperature (or equivalent rectal, tympanic membrane, axillary) greater than age-specific critical value:
Infection at an anatomical site skin requiring specialized management or specialized antimicrobial therapy, including:
Complicated skin or soft tissue infection, such as:
History of underlying immunocompromising condition or immunodeficiency, for example:
Contacts and Locations| Contact: Henry Chambers | (415) 206-5437 |
| United States, California | |
| San Francisco General Hospital | Recruiting |
| San Francisco, California, United States, 94110 | |
| Harbor-UCLA Medical Center | Recruiting |
| Torrance, California, United States, 90509 | |
| United States, Illinois | |
| University of Chicago | Recruiting |
| Chicago, Illinois, United States, 60637 | |
More Information
| Responsible Party: | HHS/NIAID/DMID ( Robert Johnson ) |
| Study ID Numbers: | 07-0051, UCSF CA-MRSA |
| Study First Received: | August 7, 2008 |
| Last Updated: | February 4, 2010 |
| ClinicalTrials.gov Identifier: | NCT00730028 History of Changes |
| Health Authority: | United States: Federal Government; United States: Food and Drug Administration; United States: Institutional Review Board |
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Methicillin-resistant Staphyloccus aureus (MRSA), cellulitis, abscess |
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Bacterial Infections Anti-Infective Agents Antiprotozoal Agents Clindamycin Trimethoprim Soft Tissue Infections Molecular Mechanisms of Pharmacological Action Clindamycin-2-phosphate Sulfamethoxazole Anti-Infective Agents, Urinary Trimethoprim-Sulfamethoxazole Combination Enzyme Inhibitors |
Folic Acid Antagonists Renal Agents Infection Pharmacologic Actions Antimalarials Anti-Bacterial Agents Staphylococcal Infections Protein Synthesis Inhibitors Antiparasitic Agents Gram-Positive Bacterial Infections Methicillin Therapeutic Uses |