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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,310
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.
Placebo capsules will be identical in appearance to the CLINDA and TMP-SMX. Administered 3 times daily for 10 days.
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.
San Francisco General Hospital - Infectious Diseases
San Francisco, California, United States
Harbor UCLA Medical Center - Medicine - Infectious Diseases
Torrance, California, United States
Morehouse School of Medicine - Morehouse Medical Associates - Atlanta
Atlanta, Georgia, United States
The University of Chicago - Comer Children's Hospital - Infectious Diseases
Chicago, Illinois, United States
Washington University School of Medicine in St. Louis - Infectious Diseases
St Louis, Missouri, United States
Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center
Nashville, Tennessee, United States
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.
Time frame: 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.
Time frame: Test of cure (TOC) (7-10 days after completion of therapy)
Number of Participants Reporting Adverse Events.
Subjects were issued a Memory Aid to record symptoms for 10 days post product administration. At study visits, the staff reviewed the memory aid and elicited as much information as possible about any reported symptoms. Occurrence of adverse events was solicited in the memory aid and during study visits. Reported symptoms, both solicited and unsolicited, were recorded as Adverse Events.
Time frame: 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.
Participants were issued a Memory Aid to record symptoms for 10 days post product administration. At study visits, the staff reviewed the memory aid and elicited as much information as possible about any reported symptoms. Occurrence of adverse events was solicited in the memory aid and during study visits. Reported symptoms, both solicited and unsolicited, were recorded as Adverse Events. For these results, adverse events that resulted in discontinuation of study treatment for the participant were considered treatment limiting.
Time frame: 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.
Measures of clinical cure and clinical failure are the same as those defined for the primary efficacy outcome measure.
Time frame: 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.
Measures of clinical cure and clinical failure are the same as those defined for the primary efficacy outcome measure.
Time frame: 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.
Measures of clinical cure and clinical failure are the same as those defined for the primary efficacy outcome measure, with one addition. At the OMFU, relapse (the return of the original infection after initial improvement) or recurrence (return of skin infection at original site after cure of original infection) of SSTI was scored as clinical failure.
Time frame: OMFU visit
Percentage of Participants Achieving Clinical Cure at the One Month Follow-up (OMFU) Visit for the Intent-to-Treat (ITT) Population.
Measures of clinical cure and clinical failure are the same as those defined for the primary efficacy outcome measure, with one addition. At the OMFU, relapse (the return of the original infection after initial improvement) or recurrence (return of skin infection at original site after cure of original infection) of SSTI was scored as clinical failure.
Time frame: OMFU visit
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