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

Sponsor

Frieder Schaumburg (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05899140

Collaborator

(none)

100

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Skin Infection Staphylococcal Infections Staphylococcus Aureus Infection	Drug: Clindamycin Other: Standard of care	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

2-arm randomized controlled trial2-arm randomized controlled trial

Masking:

None (Open Label)

Masking Description:

This is an exploratory study and will not use a placebo

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Mar 29, 2024

Anticipated Study Completion Date :

Jul 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Other: Standard of care 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	Other: Standard of care Standard of care
Active Comparator: Standard of care + clindamycin 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.	Drug: Clindamycin 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 Other: Standard of care Standard of care

Arm

Intervention/Treatment

Other: Standard of care

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

Other: Standard of care

Standard of care

Active Comparator: Standard of care + clindamycin

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.

Drug: Clindamycin

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

Other: Standard of care

Standard of care

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults (age ≥18 years);
Need for a treatment (incision/drainage ± antibiotic treatment po or iv) of an SSTI;
1. 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