Clinical trial NCT00729937
Conditions: Staphylococcal Infection
Keywords: Methicillin, Staphylococcus aureus, MRSA
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2009-04-01; Completion date: 2013-06-01
Enrollment: 2265 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the optimal outpatient treatment strategy of uncomplicated skin and soft tissue infection (SSTI) in areas of the United States where the prevalence of Community-Acquired Methicillin-Resistant Staphylococcus (S.) aureus (CA-MRSA) is high. Infection with the S. aureus bacteria that is resistant to antibiotics is a cause of SSTIs. Three oral antibiotics will be tested for off patent treatment. Patients will receive Trimethoprim/Sulfamethoxazole (TMP/SMX), placebo (substance containing no medication), clindamycin, or cephalexin or some combination of these. The study population will include 2,235 volunteers, children 13 years of age and over and adults presenting to 5 large urban Emergency Departments. Therapy for acute uncomplicated SSTIs, including abscess, infected wound, and cellulitis will start on the day of enrollment. Participants may be involved in study related procedures for about 9 weeks.

Detailed description:
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged as a cause of skin and soft-tissue infection (SSTI). In the current era of increasing CA-MRSA infections, the outpatient management of SSTIs has not been well studied. This will be a clinical trial to evaluate oral off-patent antibiotics for outpatient treatment of patients with any of the 3 main types of acute uncomplicated SSTI, i.e., abscesses, infected wounds, and cellulitis. Upon enrollment, subjects will be stratified by type of infection, and then randomized to various treatments. Subjects with an acute uncomplicated cutaneous abscess receiving incision and drainage (I\&D) will be treated with Trimethoprim/Sulfamethoxazole (TMP/SMX) or placebo to determine whether the addition of an antibiotic with activity against CA-MRSA is more clinically efficacious than I\&D alone. Subjects with an acute wound infection will be treated with TMP/SMX or clindamycin to determine if clindamycin, an antibiotic with activity against CA-MRSA, methicillin-susceptible Staphylococcus aureus (MSSA), and streptococci is more clinically efficacious than TMP/SMX, an antibiotic with activity against CA-MRSA and MSSA. Subjects with acute cellulitis will be treated with cephalexin/TMP/SMX or cephalexin/placebo to determine if cephalexin/TMP/SMX is more clinically efficacious than cephalexin alone. The primary objectives for each type of SSTI studied are to compare the cure rates in the per protocol (PP) population. Secondary objectives provide additional means of assessment for the clinical efficacy of the employed interventions and resolution of the infection and include describing microbiological cure, change in the dimension of erythema, composite cure, surgical procedures, invasive and recurrent infections, infections in household contacts, and time to normal activity and until analgesics are no longer used at various times in the PP/ modified intent-to-treat (mITT) populations. This is a multi-center, randomized, double-blind clinical trial in which subjects will be stratified by the type of infection and then randomized to various 7-day oral antibiotic treatments, including placebo-controlled and comparative designs. The study population will include children 13 years of age and over and adults, who weigh greater than or equal to 40 kg presenting to 5 large urban emergency departments. Therapy will start on the day of enrollment. Subjects will be evaluated upon enrollment, at 2-3 days after enrollment (OTV), at 1-3 days after the end-of-therapy (EOT), at 7-14 days after the end-of-therapy (TOC), and at 6-8 weeks after the end-of-therapy (EFV).

Arms: arm 1: Subjects with an acute uncomplicated cutaneous abscess will be randomized to receive either Trimethoprim/Sulfamethoxazole (TMP/SMX) (4 single strength pills, 80 mg/400 mg each, twice per day) or 4 placebo pills (twice per day). arm 2: Subjects with an acute uncomplicated wound infection will be randomized to receive Trimethoprim/Sulfamethoxazole (TMP/SMX) (4 single strength pills, 80 mg/400 mg each, twice per day, with alternating 1 identical placebo pill, twice per day) or clindamycin (300 mg, four times per day, with 3 placebo pills on alternating doses). arm 3: Subjects with acute uncomplicated cellulitis will be randomized to receive cephalexin (500 mg, four times per day) and Trimethoprim/Sulfamethoxazole (TMP/SMX) (4 single strength pills, 80 mg/400 mg each, twice per day) or cephalexin (500 mg, four times per day) and placebo (4 pills, twice per day).
Interventions: intervention 1: Cephalexin intervention 2: Clindamycin intervention 3: Placebo intervention 4: Trimethoprim-sulfamethoxazole
Intervention descriptions: intervention 1: 500 mg, four times per day. intervention 2: 300 mg, four times per day. intervention 3: Placebo tablet administered orally. intervention 4: 4 single strength Trimethoprim/Sulfamethoxazole (TMP/SMX), 80 mg/400 mg each, twice per day.

Protocol documents: