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

Adjunctive Clindamycin Versus Standard of Care for the Treatment of Skin and Soft Tissue Infections, a Randomized Controlled, Open-label Superiority Phase 4 Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Staphylococcal Infections; Staphylococcus Aureus Infection; Skin Infection
• Intervention / Treatment: Other: Standard of care; Drug: Clindamycin

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Frieder Schaumburg, MD; Phone Number: +492518352767; Email: frieder.schaumburg@ukmuenster.de
• Study Contact Backup: Name: Ioana D Olaru, PhD; Email: ioanadiana.olaru@ukmuenster.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Other: Standard of care; Standard of care; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical cure at follow-up 7 days	Proportion of patients with clinical cure defined as the absence of clinical failure	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in inflammatory markers under therapy	Change in mean C-reactive protein level	from baseline to Day 3 and from baseline to Day 7
Time to symptom resolution	Time to resolution of symptoms	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	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;	during follow-up day 3 and day 7
Clostridioides difficile associated diarrhoea	Proportion with Clostridioides difficile associated diarrhoea	during follow-up, up to day 14
Recurrent infections	Proportion of recurrent infections during a passive follow up of 6 months	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	Day 14

Collaborators and Investigators

• Sponsor: Frieder Schaumburg
• Investigators: Principal Investigator: Frieder Schaumburg, MD, University of Münster

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): March 29, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: May 22, 2023
• First Submitted That Met QC Criteria: June 1, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Staphylococcus aureus; SSTI; Panton-Valentine leukocidin
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Inflammation; Disease Attributes; Connective Tissue Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Suppuration; Infections; Communicable Diseases; Cellulitis; Skin Diseases, Infectious; Soft Tissue Infections; Staphylococcal Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Clindamycin; Clindamycin palmitate; Clindamycin phosphate
• Other Study ID Numbers: SoTiClin

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is currently being considered and the information will be updated once a decision has been reached

Drug and device information, study documents

• 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