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Adjunctive Clindamycin for the Treatment of Skin and Soft Tissue Infections, a Randomized Controlled Trial (SoTiClin)

Primary Purpose

Skin Infection, Staphylococcal Infections, Staphylococcus Aureus Infection

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Clindamycin
Standard of care
Sponsored by
Frieder Schaumburg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Skin Infection focused on measuring SSTI, Staphylococcus aureus, Panton-Valentine leukocidin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Adults (age ≥18 years); Need for a treatment (incision/drainage ± antibiotic treatment po or iv) of an SSTI; S. aureus causing SSTI identified from at least one clinical specimen (including isolation in polymicrobial cultures if S. aureus is considered to be the leading pathogen); Onset of symptoms within the last 4 weeks; Randomisation possible within 72 hours from collection of the initial culture Ability to conduct the follow-up visits either during admission or at home Initial culture collected within 48 hours of hospital admission Willingness to participate in the study. Exclusion Criteria Previous allergic reaction to clindamycin Previous antibiotic-associated diarrhea Previous study participation Pregnancy as confirmed by a beta-HCG rapid test. Started treatment with clindamycin prior to clinic presentation; Documented systemic antibiotic treatment within the previous 14 days Co-administration of other protein synthesis inhibitors (e.g. macrolides, rifampicin, linezolid, aminoglycosides, tetracyclines, chloramphenicol); Co-administration of toxin inducers (trimethoprim-sulfamethoxazole) Severe illness (patient expected to die in the following 24 hrs); Chronically infected wounds (>4 weeks of symptoms); Infections associated with any of the following (due to mixed infection): a) Human or animal bites;b) Prosthetic or implantable devices; c) Decubitus ulcers; d) Diabetic foot ulcers, infected ulcers secondary to peripheral artery disease, chronic venous insufficiency; e) Suspected Buruli ulcer; f) Infected burns. Hospital-acquired infection including post-surgical site infections

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Other

    Active Comparator

    Arm Label

    Standard of care

    Standard of care + clindamycin

    Arm Description

    Participants with skin and soft-tissue infections requiring systemic treatment (oral or intravenous). Treatment according to local guidelines = standard of care: usually an anti-staphylococcal penicillin with or without incision and drainage, as required. Treatment can be with (local guidelines) cloxacillin (non-severe) po 500g QIDfor 5-7 days ceftriaxone (severe infections) 2g iv OD with step-down to cloxacillin po 500 mg QID for a total of 7 days

    Participants with skin and soft-tissue infections requiring systemic treatment (oral or intravenous). Addition of clindamycin: 10 mg/kg/dose QID iv (maximum 600mg QID iv) or oral clindamycin 450 mg TDS for adults for a total of 7 days from randomisation.

    Outcomes

    Primary Outcome Measures

    Clinical cure at follow-up 7 days
    Proportion of patients with clinical cure defined as the absence of clinical failure

    Secondary Outcome Measures

    Change in inflammatory markers under therapy
    Change in mean C-reactive protein level
    Time to symptom resolution
    Time to resolution of symptoms
    Occurence of adverse events
    Proportion of patients with adverse events (of any kind) and of adverse events that required treatment discontinuation or change in drugs used
    Microbiological failure
    Proportion of microbiological treatment failure (culture of S. aureus in relevant materials) on Day 3 and Day 7;
    Clostridioides difficile associated diarrhoea
    Proportion with Clostridioides difficile associated diarrhoea
    Recurrent infections
    Proportion of recurrent infections during a passive follow up of 6 months
    Clinical cure at follow-up 14 days
    Proportion of patients with clinical cure defined as the absence of clinical failure

    Full Information

    First Posted
    May 22, 2023
    Last Updated
    June 15, 2023
    Sponsor
    Frieder Schaumburg
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05899140
    Brief Title
    Adjunctive Clindamycin for the Treatment of Skin and Soft Tissue Infections, a Randomized Controlled Trial
    Acronym
    SoTiClin
    Official Title
    Adjunctive Clindamycin Versus Standard of Care for the Treatment of Skin and Soft Tissue Infections, a Randomized Controlled, Open-label Superiority Phase 4 Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 1, 2023 (Anticipated)
    Primary Completion Date
    March 29, 2024 (Anticipated)
    Study Completion Date
    July 31, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Frieder Schaumburg

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is an exploratory study to evaluate the effect of adjunctive clindamycin in the treatment of skin and soft-tissue infections due to Staphylococcus aureus in patients from Sierra Leone. The study hypothesizes that clindamycin, when added to routine treatment, will lead to a more rapid clinical resolution and less frequent recurrences of infection.
    Detailed Description
    Panton-Valentine Leukokidin and other toxins play an important role in the severity of skin and soft-tissue infections due to Staphylococcus aureus. The inhibition of the protein synthesis could be beneficial, due to the major role of protein-toxins in the pathogenesis of skin and soft tissue infections. Clindamycin has a strong toxin-suppressive activity. Therefore, clindamycin is currently considered as the most-promising adjuvant antimicrobial agent in the treatment of toxin-mediated S. aureus infections. Recurrent infections are common in patients with S. aureus skin and soft-tissue infections. Clindamycin has been reported to reduce S. aureus colonisation, which may in turn reduce the risk for recurrent infections. Clindamycin is an already approved antimicrobial used for a wide range of indications and with a known safety profile. This study is an investigator-led, investigator-initiated, open-label superiority randomised controlled trial that will be conducted at Masanga Hospital in Sierra Leone. The objectives of this study are to determine the feasibility, efficacy and safety of adjunctive clindamycin therapy (in addition to standard-of-care) compared to standard-of-care alone on clinical treatment outcomes in patients with skin and soft tissue infections due to S. aureus in Sierra Leone. This is a preliminary study, which will include 100 adult participants with skin and soft-tissue infections requiring systemic therapy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Skin Infection, Staphylococcal Infections, Staphylococcus Aureus Infection
    Keywords
    SSTI, Staphylococcus aureus, Panton-Valentine leukocidin

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Model Description
    2-arm randomized controlled trial
    Masking
    None (Open Label)
    Masking Description
    This is an exploratory study and will not use a placebo
    Allocation
    Randomized
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Standard of care
    Arm Type
    Other
    Arm Description
    Participants with skin and soft-tissue infections requiring systemic treatment (oral or intravenous). Treatment according to local guidelines = standard of care: usually an anti-staphylococcal penicillin with or without incision and drainage, as required. Treatment can be with (local guidelines) cloxacillin (non-severe) po 500g QIDfor 5-7 days ceftriaxone (severe infections) 2g iv OD with step-down to cloxacillin po 500 mg QID for a total of 7 days
    Arm Title
    Standard of care + clindamycin
    Arm Type
    Active Comparator
    Arm Description
    Participants with skin and soft-tissue infections requiring systemic treatment (oral or intravenous). Addition of clindamycin: 10 mg/kg/dose QID iv (maximum 600mg QID iv) or oral clindamycin 450 mg TDS for adults for a total of 7 days from randomisation.
    Intervention Type
    Drug
    Intervention Name(s)
    Clindamycin
    Intervention Description
    Clindamycin will be administered at a dose of 450 mg TDS (oral) or 10 mg/kg/dose QID iv (maximum 600mg QID iv) for a maximum of 7 days
    Intervention Type
    Other
    Intervention Name(s)
    Standard of care
    Intervention Description
    Standard of care
    Primary Outcome Measure Information:
    Title
    Clinical cure at follow-up 7 days
    Description
    Proportion of patients with clinical cure defined as the absence of clinical failure
    Time Frame
    Day 7
    Secondary Outcome Measure Information:
    Title
    Change in inflammatory markers under therapy
    Description
    Change in mean C-reactive protein level
    Time Frame
    from baseline to Day 3 and from baseline to Day 7
    Title
    Time to symptom resolution
    Description
    Time to resolution of symptoms
    Time Frame
    during follow-up up to day 14
    Title
    Occurence of adverse events
    Description
    Proportion of patients with adverse events (of any kind) and of adverse events that required treatment discontinuation or change in drugs used
    Time Frame
    anytime during follow-up (to day 14)
    Title
    Microbiological failure
    Description
    Proportion of microbiological treatment failure (culture of S. aureus in relevant materials) on Day 3 and Day 7;
    Time Frame
    during follow-up day 3 and day 7
    Title
    Clostridioides difficile associated diarrhoea
    Description
    Proportion with Clostridioides difficile associated diarrhoea
    Time Frame
    during follow-up, up to day 14
    Title
    Recurrent infections
    Description
    Proportion of recurrent infections during a passive follow up of 6 months
    Time Frame
    6 months passive follow-up (participant re-presents to clinic)
    Title
    Clinical cure at follow-up 14 days
    Description
    Proportion of patients with clinical cure defined as the absence of clinical failure
    Time Frame
    Day 14

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Adults (age ≥18 years); Need for a treatment (incision/drainage ± antibiotic treatment po or iv) of an SSTI; S. aureus causing SSTI identified from at least one clinical specimen (including isolation in polymicrobial cultures if S. aureus is considered to be the leading pathogen); Onset of symptoms within the last 4 weeks; Randomisation possible within 72 hours from collection of the initial culture Ability to conduct the follow-up visits either during admission or at home Initial culture collected within 48 hours of hospital admission Willingness to participate in the study. Exclusion Criteria Previous allergic reaction to clindamycin Previous antibiotic-associated diarrhea Previous study participation Pregnancy as confirmed by a beta-HCG rapid test. Started treatment with clindamycin prior to clinic presentation; Documented systemic antibiotic treatment within the previous 14 days Co-administration of other protein synthesis inhibitors (e.g. macrolides, rifampicin, linezolid, aminoglycosides, tetracyclines, chloramphenicol); Co-administration of toxin inducers (trimethoprim-sulfamethoxazole) Severe illness (patient expected to die in the following 24 hrs); Chronically infected wounds (>4 weeks of symptoms); Infections associated with any of the following (due to mixed infection): a) Human or animal bites;b) Prosthetic or implantable devices; c) Decubitus ulcers; d) Diabetic foot ulcers, infected ulcers secondary to peripheral artery disease, chronic venous insufficiency; e) Suspected Buruli ulcer; f) Infected burns. Hospital-acquired infection including post-surgical site infections
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Frieder Schaumburg, MD
    Phone
    +492518352767
    Email
    frieder.schaumburg@ukmuenster.de
    First Name & Middle Initial & Last Name or Official Title & Degree
    Ioana D Olaru, PhD
    Email
    ioanadiana.olaru@ukmuenster.de
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Frieder Schaumburg, MD
    Organizational Affiliation
    University of Münster
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    This is currently being considered and the information will be updated once a decision has been reached

    Learn more about this trial

    Adjunctive Clindamycin for the Treatment of Skin and Soft Tissue Infections, a Randomized Controlled Trial

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