Prophylactic Antibiotic Treatment in Hemodialysis

Hemodialysis Clinical Trial

— PANTHEM  

Official title:

Prophylactic Antibiotic Treatment in End Stage Kidney Disease and Central Venous Catheter as Hemodialysis Vascular Access

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05248620
• Other study ID #: H-20026735
• Status: Recruiting
• Phase: N/A
• Start date: February 14, 2022
• Est. completion date: May 2029

Study information

• Verified date: January 2024
• Source: Zealand University Hospital
• Contact: Niels E Bruun, Professor
• Phone: +4525159309
• Email: nbru[@]regionsjaelland.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy of prophylactic antibiotic treatment on blood stream infections and severe culture negative infections, in patients on newly started hemodialysis(HD), with a central venous catheter as vascular access.

Description:

After being informed about the study and potential risks all eligible patients, giving written informed consent will be included in the study. At week 0 patients will be randomized in a single blinded manner (participants and care providers) in a 1:1 manner to receive 500/125mg amoxicillin/clavulanic acid 30-120 minutes before each hemodialysis with a central venous catheter (CVC) as vascular access, or corresponding placebo. The timing of antibiotic administration has been established in a pilot-study in order to secure a sufficient concentration of antibiotics during the dialysis session. In case of side effects to amoxicillin/clavulanic acid, the prophylactic antibiotic will be shifted to 600mg clindamycin. Total treatment period with prophylactic antibiotics is 6 months, with a 1 year follow-up.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: May 2029
• Est. primary completion date: October 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• End Stage Kidney Disease (ESKD) patients who receive an uncuffed or cuffed CVC for expected chronic HD, regardless of previous ESKD treatment modality (PD or KTX) and hemodialysis access (AV-fistula or AV-graft))

• =18 years

• Ability to understand the study background, risk and benefit of treatment and to give written informed consent

Exclusion Criteria:

• Unable to give informed consent

• Known intolerance to beta-lactam antibiotics and clindamycin

• Active infection treated with antibiotics

• Breastfeeding

• Pregnancy. In women of childbearing age, an approved birth control must be ensured at least 1 month before and during all the 6 months of antibiotic/placebo treatment.

Patients may be rescreened later i.e. within a time period of one month from start of HD, if exclusion criteria are reversible.

Related Conditions & MeSH terms

• Hemodialysis

Intervention

Drug:
• Amoxicillin Clavulanic 500/125mg or placebo
Prophylactic antibiotic treatment

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg	North Region
Denmark	Aarhus University Hospital	Aarhus	Middle Region
Denmark	Herlev-Gentofte Hospital	Copenhagen	Capital Region
Denmark	Rigshospitalet	Copenhagen	Capital Region
Denmark	North Zealand Hospital Hillerød	Hillerød	Capital Region
Denmark	Odense University Hospital	Odense	Region South
Denmark	ZUH Roskilde	Roskilde	Region Sjaelland

Sponsors (1)

Lead Sponsor	Collaborator
Zealand University Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (10)

Aslam S, Vaida F, Ritter M, Mehta RL. Systematic review and meta-analysis on management of hemodialysis catheter-related bacteremia. J Am Soc Nephrol. 2014 Dec;25(12):2927-41. doi: 10.1681/ASN.2013091009. Epub 2014 May 22. — View Citation

Chaudry MS, Carlson N, Gislason GH, Kamper AL, Rix M, Fowler VG Jr, Torp-Pedersen C, Bruun NE. Risk of Infective Endocarditis in Patients with End Stage Renal Disease. Clin J Am Soc Nephrol. 2017 Nov 7;12(11):1814-1822. doi: 10.2215/CJN.02320317. Epub 2017 Oct 3. — View Citation

Chaudry MS, Gislason GH, Kamper AL, Rix M, Dahl A, Ostergaard L, Fosbol EL, Lauridsen TK, Oestergaard LB, Hassager C, Torp-Pedersen C, Bruun NE. The impact of hemodialysis on mortality risk and cause of death in Staphylococcus aureus endocarditis. BMC Nephrol. 2018 Sep 3;19(1):216. doi: 10.1186/s12882-018-1016-0. — View Citation

de Jager DJ, Grootendorst DC, Jager KJ, van Dijk PC, Tomas LM, Ansell D, Collart F, Finne P, Heaf JG, De Meester J, Wetzels JF, Rosendaal FR, Dekker FW. Cardiovascular and noncardiovascular mortality among patients starting dialysis. JAMA. 2009 Oct 28;302(16):1782-9. doi: 10.1001/jama.2009.1488. — View Citation

Gupta V, Yassin MH. Infection and hemodialysis access: an updated review. Infect Disord Drug Targets. 2013 Jun;13(3):196-205. doi: 10.2174/1871526511313030008. — View Citation

Jaber BL. Bacterial infections in hemodialysis patients: pathogenesis and prevention. Kidney Int. 2005 Jun;67(6):2508-19. doi: 10.1111/j.1523-1755.2005.00364.x. No abstract available. — View Citation

Nelveg-Kristensen KE, Laier GH, Heaf JG. Risk of death after first-time blood stream infection in incident dialysis patients with specific consideration on vascular access and comorbidity. BMC Infect Dis. 2018 Dec 20;18(1):688. doi: 10.1186/s12879-018-3594-7. — View Citation

Sakhuja A, Nanchal RS, Gupta S, Amer H, Kumar G, Albright RC, Kashani KB. Trends and Outcomes of Severe Sepsis in Patients on Maintenance Dialysis. Am J Nephrol. 2016;43(2):97-103. doi: 10.1159/000444684. Epub 2016 Mar 10. — View Citation

Sarnak MJ, Jaber BL. Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int. 2000 Oct;58(4):1758-64. doi: 10.1111/j.1523-1755.2000.00337.x. — View Citation

Vogelzang JL, van Stralen KJ, Noordzij M, Diez JA, Carrero JJ, Couchoud C, Dekker FW, Finne P, Fouque D, Heaf JG, Hoitsma A, Leivestad T, de Meester J, Metcalfe W, Palsson R, Postorino M, Ravani P, Vanholder R, Wallner M, Wanner C, Groothoff JW, Jager KJ. Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry. Nephrol Dial Transplant. 2015 Jun;30(6):1028-37. doi: 10.1093/ndt/gfv007. Epub 2015 Jan 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients with Sepsis	Hospitalization due to sepsis or septic shock	= 6 months after randomization
Other	Number of patients with Deep tissue infection	Infective endocarditis, osteomyelitis, and spondylodiscitis	= 6 months after randomization
Other	Number of patients with Autoinfection	Frequency of BSI autoinfection	= 6 months after randomization
Other	Number of patients with Clostridium difficile infection	Clostridium difficile infection - numbers and days of admission	= 6 months after randomization
Other	Mortality due to infection - number of patients	Mortality due to infection	= 6 months after randomization
Other	Number of CVC removals	CVC removal due to CVC infection	= 6 months after randomization
Other	Use of Antibiotics in Difined Daily Doses	Total use of antibiotics in Defined Daily Doses	= 6 months after randomization
Other	Healt-care economics	Health-care related economic consequences due to hospitalization and treatment of the disease	= 6 months after randomization
Other	Number of patients with Extended Spectrum Beta-Lactamase (ESBL) infection	ESBL infections - number of patients and days of admission	= 6 months after randomization
Other	Number of patients with Methicillin-resistant Staphylococcus aureus (MRSA) infection	MRSA infections - number of patients and days of admission	= 6 months after randomization
Other	Number of patients with Carbapenemase-Producing Organisms (CPO) infection	CPO infections - number og patients and days of admission	= 6 months after randomization
Other	Number of patients with Vancomycin-resistant enterococci (VRE) infection	VRE infections - number of patients and days of admission	= 6 months after randomization
Other	Number of patients with Cardiovascular events	Hospitalization with acute myocardial infarction, worsening heart failure or stroke	= 6 months after randomization
Primary	Number of patients with Blood stream infection (BSI)	Hospitalization for BSI	= 6 months after randomization
Primary	Number of patients with Severe blood culture negative infection	Hospitalization = 3 days due to infection defined as: C-reactive protein (CRP) = 75 and negative blood cultures, treated with iv antibiotics	= 6 months after randomization
Secondary	Number of patients with BSI or severe blood culture negative infection	Each of the components in the primary endpoint	= 6 months after randomization
Secondary	Mortality	All-cause mortality	= 6 months after randomization