Staphylococcal Infection | Uncomplicated Skin and Soft Tissue Infections Caused by Community-Associated Methicillin-Resistant Staphylococcus Aureus
Staphylococcal Infection research study
What is the primary objective of this study?
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.
Who is eligible to participate?
Inclusion Criteria: - 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: 1. Erythema 2. Swelling or induration 3. Local warmth 4. Purulent drainage 5. Tenderness to palpation or pain - Able to take oral antibiotic therapy, either in pill or suspension form. Exclusion Criteria: - 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: 1. Impetigo 2. Ecthyma 3. Folliculitis 4. 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: 1. Age 6 - 11 months: < 70 mm Hg 2. Age 1 to 8 years: < 80 mm Hg 3. Age 9 to 17 years: < 90 mm Hg 4. Age greater than or equal to 18 years: < 90 mm Hg - Heart rate less than 45 beats per minute (BPM). - Heart rate greater than an age-specific critical value: 1. Age 6 - 11 months: > 140 BPM 2. Age 1 to 8 years: > 120 BPM 3. Age 9 to 17 years: > 120 BPM 4. Age greater than or equal to 18 years: > 120 BPM. - Oral temperature (or equivalent rectal, tympanic membrane, axillary) less than 35.5 degrees Celsius (95.9 degrees Fahrenheit). - Oral temperature (or equivalent rectal, tympanic membrane, axillary) greater than age-specific critical value: 1. Age 6 - 11 months: > 38.0 degrees Celsius (100.4 degrees Fahrenheit) 2. Age 1 to 8 years: > 38.5 degrees Celsius (101.3 degrees Fahrenheit) 3. Age 9 to 17 years: > 38.5 degrees Celsius (101.3 degrees Fahrenheit) 4. Age greater than or equal to 18 years: > 38.5 degrees Celsius (101.3 degrees Fahrenheit). - Documented human or witnessed animal bite in the past 30 days at the site of infection. - Systemic antibacterial therapy with antistaphylococcal activity within the prior 14 days. - The following concomitant medications: warfarin, phenytoin, methotrexate, rosiglitazone or sulfonylureas and systemically administered antibacterial agents with activity against staphylococci. - Diagnosed or suspected disseminated or severe Staphylococcus aureus or group A streptococcal (GAS) infection, including lymphangitic spread of skin infection, septicemia, bacteremia, pneumonia, endocarditis, osteomyelitis, septic arthritis, gangrene, necrotizing fasciitis, myositis, or other serious infections. - Infection at an anatomical skin site requiring specialized management or specialized antimicrobial therapy, including: 1. Periauricular or orbital infection 2. Perirectal infection 3. Suspected deep space infection of the hand or foot 4. Genital infection 5. Mastitis 6. Bursitis - Radiographic evidence or suspicion of gas in the tissue or foreign body infection (note: radiography is not required for screening and can be performed at the discretion of the treating physician). - Gastrointestinal symptoms such as nausea, vomiting, or diarrhea of a severity that would preclude consumption of oral antibiotics. - Hypersensitivity or history of allergic reaction to study drug. - History of glucose-6-phosphate dehydrogenase (G6PD) deficiency. - Third trimester pregnancy: pregnant women must have gestational age estimated by an objective means, e.g. ultrasound, fundal height, and women who are within 4 weeks of the third trimester of pregnancy, defined as week 27 of pregnancy, are not eligible. - Currently breast feeding. - Severe or morbid obesity with a body mass index (BMI) >40 kg/m^2. - Complicated skin or soft tissue infection, such as: 1. Catheter or catheter site infection within 30 days of placement 2. Surgical site infection 3. Known or suspected prosthetic device infection 4. Suspected Gram-negative or anaerobic pathogen 5. Unusual exposure history (e.g., underwater injury, fish-tank exposure, heavy soil exposure, etc) 6. Infection at the site of an area of underlying skin disease such as chronic eczema, psoriasis, atopic dermatitis, or chronic venous stasis - History of underlying immunocompromising condition or immunodeficiency, for example: 1. Diabetes mellitus 2. Chronic renal failure, creatinine clearance <30 ml/min 3. Renal dialysis within the past 180 days 4. Human immunodeficiency virus (HIV)-positive with either cluster of differentiation (CD)4 count <200 or <4 percent CD4 in the past 180 days or HIV-positive and no documented CD4 count in the past 4 months 5. Organ or bone marrow transplantation (ever), immunosuppressive therapy within the past 180 days, severe liver disease 6. Other serious underlying disease, as determined by the treating physician or the investigator
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Trimethoprim-sulfamethoxazoleTrimethoprim-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.
Other:PlaceboPlacebo capsules will be identical in appearance to the CLINDA and TMP-SMX. Administered 3 times daily for 10 days.
Drug:ClindamycinCLINDA (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.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Limited AbscessLimited 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.
Cellulitis or Larger AbscessSubjects 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.
Start Date: April 2009
Completed Date: February 2015
Phase: Phase 2
Primary Outcome: Percentage of Participants Achieving Clinical Cure, Defined as Absence of Clinical Failure, in the Evaluable Population.
Secondary Outcome: Number of Participants Reporting Adverse Events.
Study sponsors, principal investigator, and references
Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
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.