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Staphylococcal InfectionPhase 2NCT00730028

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

A Phase 2 study testing Trimethoprim-sulfamethoxazole and Clindamycin in people with Staphylococcal Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 months to 85 years
Conditions the study is for
Staphylococcal Infection
What is being tested?
Trimethoprim-sulfamethoxazole and Clindamycin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,310 participants
Where
6 sitesUnited States
Study dates
Apr 2009to Feb 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 85 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • Local warmth
  • Purulent drainage
  • Tenderness to palpation or pain
  • Able to take oral antibiotic therapy, either in pill or suspension form.

Who cannot join

  • 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.
Show all 63Show fewer
  • 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:
  • Age 6 - 11 months: < 70 mm Hg
  • Age 1 to 8 years: < 80 mm Hg
  • Age 9 to 17 years: < 90 mm Hg
  • 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:
  • Age 6 - 11 months: > 140 BPM
  • Age 1 to 8 years: > 120 BPM
  • Age 9 to 17 years: > 120 BPM
  • 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:
  • Age 6 - 11 months: > 38.0 degrees Celsius (100.4 degrees Fahrenheit)
  • Age 1 to 8 years: > 38.5 degrees Celsius (101.3 degrees Fahrenheit)
  • Age 9 to 17 years: > 38.5 degrees Celsius (101.3 degrees Fahrenheit)
  • 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:
  • Periauricular or orbital infection
  • Perirectal infection
  • Suspected deep space infection of the hand or foot
  • Genital infection
  • Mastitis
  • 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:
  • Catheter or catheter site infection within 30 days of placement
  • Surgical site infection
  • Known or suspected prosthetic device infection
  • Suspected Gram-negative or anaerobic pathogen
  • Unusual exposure history (e.g., underwater injury, fish-tank exposure, heavy soil exposure, etc)
  • 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:
  • Diabetes mellitus
  • Chronic renal failure, creatinine clearance <30 ml/min
  • Renal dialysis within the past 180 days
  • 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
  • Organ or bone marrow transplantation (ever), immunosuppressive therapy within the past 180 days, severe liver disease
  • Other serious underlying disease, as determined by the treating physician or the investigator

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Morehouse School of Medicine - Morehouse Medical Associates - Atlanta

    Atlanta, Georgia, 30303-2544

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

    Chicago, Illinois, 60637-1425

  • Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

    Nashville, Tennessee, 37232-2573

  • San Francisco General Hospital - Infectious Diseases

    San Francisco, California, 94110-3518

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

    St Louis, Missouri, 63110-1010

  • Harbor UCLA Medical Center - Medicine - Infectious Diseases

    Torrance, California, 90502-2006

Other trials in United States

About this 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

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.

Read the detailed description

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.

Being tested
Trimethoprim-sulfamethoxazole, Placebo, Clindamycin
Keywords
Methicillin-resistant Staphylococcus aureus (MRSA), cellulitis, abscess, children, elderly
Medical subject headings
Staphylococcal Infections, Cellulitis, Abscess

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trimethoprim-sulfamethoxazoleDrug

    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.

  • PlaceboOther

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

  • ClindamycinDrug

    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.

Study groups in NCT00730028
Study groupRoleWhat they receive
Limited AbscessExperimentalLimited 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.
Receives: Drug: Trimethoprim-sulfamethoxazole; Other: Placebo; Drug: Clindamycin
Cellulitis or Larger AbscessExperimentalSubjects 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.
Receives: Drug: Trimethoprim-sulfamethoxazole; Drug: Clindamycin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

Secondary outcomes (6)

  1. 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.

    Measured: 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)

  2. 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.

    Measured: 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)

  3. 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.

    Measured: EOT visit within 48 hours of completion of therapy

  4. 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.

    Measured: EOT visit within 48 hours of completion of therapy

  5. 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.

    Measured: OMFU visit

  6. 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.

    Measured: OMFU visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2008 (estimated)
  2. Study startApr 2009
  3. Primary completionFeb 2015
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,310 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00730028
Sponsor's protocol ID
07-0051
Other IDs
UCSF CA-MRSA
Status last verified
Apr 2015
First submitted
7 Aug 2008
Last updated
17 Mar 2016

Publications

  • 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.

    PubMed 25785967

  • 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.

    PubMed 28657870

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trimethoprim-sulfamethoxazole and Clindamycin in people with Staphylococcal Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 63 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Achieving Clinical Cure, Defined as Absence of Clinical Failure, in the Evaluable Population. (time frame: Test of cure (TOC) (7-10 days after completion of therapy)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00730028, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2016.

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