S. Aureus Decolonization in HPN Patients. (CARRIER)

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

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.

Study Overview

• Status: Terminated
• Conditions: Staphylococcus Aureus; Motility Disorder
• Intervention / Treatment: Drug: Doxycycline; Drug: Trimethoprim; Drug: Sulfamethoxazole/trimethoprim; Drug: Clindamycin; Drug: Clarithromycin; Drug: Ciprofloxacin; Drug: Fusidic Acid; Drug: Rifampin; Drug: Chlorhexidine; Drug: Mupirocin; Drug: Betadine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500HB
      • Radboud UMC
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 100DD
      • AMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Search and destroy (SD) strategy; 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; tablet; Drug: Trimethoprim; tablet; Drug: Sulfamethoxazole/trimethoprim; tablet; Other Names: Bactrimel; Drug: Clindamycin; tablet; Drug: Clarithromycin; tablet; Drug: Ciprofloxacin; tablet; Drug: Fusidic Acid; tablet or ointment; Drug: Rifampin; tablet; Drug: Chlorhexidine; Mouthwash or bodywash; Drug: Mupirocin; Nasal ointment; Drug: Betadine; Shampoo
Active Comparator: Continuous suppression (CS) strategy; 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; Mouthwash or bodywash; Drug: Mupirocin; Nasal ointment; Drug: Betadine; Shampoo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: University College, London; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Study Director: Joost PH Drenth, MD, PhD, Sponsor GmbH

Publications and helpful links

General Publications

• Gompelman M, Wouters Y, Kievit W, Hopman J, Wertheim HF, Bleeker-Rovers CP, Wanten GJA. Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition: study protocol for a randomized multicenter trial. Trials. 2018 Jun 28;19(1):346. doi: 10.1186/s13063-018-2732-2.

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2018
• Primary Completion (Actual): October 14, 2021
• Study Completion (Actual): October 14, 2021

Study Registration Dates

• First Submitted: May 29, 2017
• First Submitted That Met QC Criteria: May 29, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 25, 2022
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Eradication; S. aureus; Home Parenteral Nutrition; Intestinal failure; Decolonization
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Staphylococcal Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Protein Synthesis Inhibitors; Cytochrome P-450 Enzyme Inducers; Antiprotozoal Agents; Antiparasitic Agents; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antimalarials; Folic Acid Antagonists; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP1A2 Inhibitors; Disinfectants; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Mupirocin; Doxycycline; Rifampin; Clindamycin; Ciprofloxacin; Chlorhexidine; Clarithromycin; Povidone-Iodine; Trimethoprim; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination; Fusidic Acid
• Other Study ID Numbers: NL 61885.091.17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No