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

Phase 4RecruitingNCT05899140

Frieder Schaumburg100 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Adults (age ≥18 years); 2. Need for a treatment (incision/drainage ± antibiotic treatment po or iv) of an SSTI; 3. 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); 4. Onset of symptoms within the last 4 weeks; 5. Randomisation possible within 72 hours from collection of the initial culture 6. Ability to conduct the follow-up visits either during admission or at home 7. Initial culture collected within 48 hours of hospital admission 8. Willingness to participate in the study. Exclusion Criteria 1. Previous allergic reaction to clindamycin 2. Previous antibiotic-associated diarrhea 3. Previous study participation 4. Pregnancy as confirmed by a beta-HCG rapid test. 5. Started treatment with clindamycin prior to clinic presentation; 6. Documented systemic antibiotic treatment within the previous 14 days 7. Co-administration of other protein synthesis inhibitors (e.g. macrolides, rifampicin, linezolid, aminoglycosides, tetracyclines, chloramphenicol); 8. Co-administration of toxin inducers (trimethoprim-sulfamethoxazole) 9. Severe illness (patient expected to die in the following 24 hrs); 10. Chronically infected wounds (\>4 weeks of symptoms); 11. 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. 12. Hospital-acquired infection including post-surgical site infections

Outcomes

Primary Outcomes

Clinical cure at follow-up 7 days

Proportion of patients with clinical cure defined as the absence of clinical failure

Time frame: Day 7

Secondary Outcomes

Change in inflammatory markers under therapy

Change in mean C-reactive protein level

Time frame: from baseline to Day 3 and from baseline to Day 7

Time to symptom resolution

Time to resolution of symptoms

Time frame: during follow-up up to day 14

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

Time frame: anytime during follow-up (to day 14)

Microbiological failure

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

Clostridioides difficile associated diarrhoea

Proportion with Clostridioides difficile associated diarrhoea

Time frame: during follow-up, up to day 14

Recurrent infections

Proportion of recurrent infections during a passive follow up of 6 months

Time frame: 6 months passive follow-up (participant re-presents to clinic)

Clinical cure at follow-up 14 days

Proportion of patients with clinical cure defined as the absence of clinical failure

Time frame: Day 14

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts