S. Aureus Decolonization in HPN Patients.

Study Overview
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Brief Summary
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This trial focusses on identifying the most effective and safe long-term S. aureus carriage decolonization strategy in home parenteral nutrition patients. Half of the participants will receive a quick and short systemic antibiotic treatment combined with topical treatment, while the other half will receive only topical treatment on a periodic basis.

Detailed Description
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Patients on home parenteral nutrition (HPN) are exposed to a lifelong risk of developing S. aureus bacteremia (SAB). SAB pose a threat to both catheter and patient survival and may lead to a permanent loss of vascular access. S. aureus carriage eradication has proven successful in prevention of S. aureus infections. S. aureus decolonization is a key strategy to maintain venous access and avoid hospitalization.

Official Title
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Long-term StaphyloCoccus Aureus decolonizAtion in Patients on Home parenteRal nutRition: a randomIzed multicEnter tRial.

Conditions
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Staphylococcus Aureus, Motility Disorder

Intervention / Treatment
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* Drug: Doxycycline
* Drug: Trimethoprim
* Drug: Sulfamethoxazole/trimethoprim
* Drug: Clindamycin
* Drug: Clarithromycin
* Drug: Ciprofloxacin
* Drug: Fusidic Acid
* Drug: Rifampin
* Drug: Chlorhexidine
* Drug: Mupirocin
* Drug: Betadine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is fully able to understand the nature of the proposed intervention. Written informed consent by the patient before entering the trial. Age ≥ 18 years. Estimated life expectancy ≥ 1 year. Patient colonized with S. aureus. Exclusion Criteria: Cannot be expected to comply with the trial plan (substance abuse, mental condition). Pregnant or breastfeeding women. Continuous exposure to Methicillin-resistant S. aureus (MRSA; e.g. pig farmer). Allergy for chlorhexidine and betadine. No options for oral and/or topical antibiotics due to allergies. Active S. aureus infection. Currently on treatment with antibiotics active against S. aureus. Decolonization (including mupirocin) treatment in the previous two months. The presence of a nasal foreign body. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) levels more than five times the upper limit of normal or liver failure.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, randomized controlled, open label superiority trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Search and destroy (SD) strategy<br>A quick and, short topical decolonization treatment combined with systemic antibiotics for S. aureus. Drug: Doxycycline 200mg once daily during one week Drug: Trimethoprim 200mg twice daily during one week Drug: Co-trimoxazol (Sulfamethoxazole/trimethoprim) 960mg twice daily during one week Drug: Clindamycin 600mg thrice daily during one week Drug: Clarithromycin 500mg twice daily during one week Drug: Ciprofloxacin 750mg twice daily during one week Drug: Fusidic acid (tablet) 500mg thrice daily during one week Drug: Rifampin 600mg twice daily during one week Drug: Mupirocin nasal ointment 20mg/g thrice daily during one week Drug: Fusidic acid ointment 20mg/g thrice daily during during five days Drug: Chlorhexidine body wash 40 mg/ml once daily during five days Drug: Betadine shampoo 75 mg/ml once daily during five days Drug: Chlorhexidine oropharyngeal rinse 2mg/ml thrice daily during five days | Drug: Doxycycline<br>* tablet<br>Drug: Trimethoprim<br>* tablet<br>Drug: Sulfamethoxazole/trimethoprim<br>* tablet<br>* Other names: Bactrimel;Drug: Clindamycin<br>* tablet<br>Drug: Clarithromycin<br>* tablet<br>Drug: Ciprofloxacin<br>* tablet<br>Drug: Fusidic Acid<br>* tablet or ointment<br>Drug: Rifampin<br>* tablet<br>Drug: Chlorhexidine<br>* Mouthwash or bodywash<br>Drug: Mupirocin<br>* Nasal ointment<br>Drug: Betadine<br>* Shampoo<br>|
| Active Comparator: Continuous suppression (CS) strategy<br>A repeated, continuous, topical decolonization treatment of S. aureus Drug: Mupirocin nasal ointment 20mg/g thrice daily during one week Drug: Fusidic acid ointment 20mg/g thrice daily during during five days Drug: Chlorhexidine body wash 40 mg/ml once daily during five days Drug: Betadine shampoo 75 mg/ml once daily during five days Drug: Chlorhexidine oropharyngeal rinse 2mg/ml thrice daily during five days | Drug: Chlorhexidine<br>* Mouthwash or bodywash<br>Drug: Mupirocin<br>* Nasal ointment<br>Drug: Betadine<br>* Shampoo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients totally eradicated for S. aureus during one year | Totally eradicated is defined as 100% of all culture swabs (nose, throat, rectum), exit-site catheter and body regions on indication) being negative for S. aureus. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients totally eradicated after one year | Proportion of patients totally eradicated for S. aureus based on negative cultures performed after one year | One year | 
| Developing long-term antimicrobial resistance | Long-term antimicrobial resistance at 6 and 12 months (measured with standard cultures and NGS) | 6 and 12 months | 
| Incidence of S. aureus infections | Incidence of S. aureus infections measured with (serious) adverse events forms every 3 months | Every 3 months during one year | 
| Overall incidence of infections | Overall incidence and time to onset of infections measured with (serious) adverse events forms every 3 months | Every three months during one year | 
| Number of catheter removals | Number of catheter removals based on data from electronic patient dossier | One year | 
| Mortality | Mortality based on data from electronic patient dossier | One year | 
| S. aureus transmission | S. aureus transmission routes from caregiver to patient (measured with NGS). | One year | 
| Patient compliance | Patient compliance (measured with medication files, counting pills, trial-specific medication diary). | Every three months during one year | 
| Adverse events | Adverse events (measured with (serious) adverse event forms every 3 months). | Every three months during one year | 
| Predictors for infections and treatment outcome | Predictors for infections and treatment failure/success (binominal regression analysis). | One year | 
| Health related quality of life | Generic health related quality of life (measured with a validated questionnaire (EQ5D-5L)). | 0, 6 and 12 months | 
| Healthcare related costs. | Cost-effectiveness analysis | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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S. aureus, Home Parenteral Nutrition, Intestinal failure, Eradication, Decolonization