Pharmacokinetics of Meropenem and Aztreonam After Intraperitoneal Administration Via Cycler-therapy in APD Patients Without Peritonitis

NCT ID: NCT07113574

Last Updated: 2025-08-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-31

Study Completion Date

2022-07-24

Brief Summary

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Peritoneal dialysis-associated peritonitis (PDAP) remains one of the most serious complications in patients undergoing peritoneal dialysis (PD), contributing significantly to hospitalization, technique failure, and mortality. Intraperitoneal (IP) antibiotic administration is the standard of care in PDAP, as it provides high local drug concentrations at the site of infection. However, dosing recommendations are largely based on pharmacokinetic (PK) studies in continuous ambulatory peritoneal dialysis (CAPD) patients. Automated peritoneal dialysis (APD), now widely used, differs significantly from CAPD in terms of dialysate volumes, frequency of exchanges, and peritoneal clearance. As a result, extrapolation of CAPD-based dosing regimens may lead to antibiotic underdosing in APD patients.

This prospective, open-label, single-center descriptive PK study investigates the plasma and dialysate concentration-time profiles of meropenem and aztreonam after IP administration into the short-dwell cycler exchanges during nighttime APD. The rationale is that administration into the early short dwells may ensure adequate antibiotic levels both during active cycling (when frequent exchanges may clear the drug rapidly) and during the subsequent long daytime dwell through back-diffusion from systemic circulation.

Twelve stable APD patients without peritonitis will be enrolled (6 per drug group). Inclusion requires patients to be on a stable APD regimen for at least one month using glucose-based dialysate for short nighttime dwells and Icodextrin for the daytime dwell. Patients with current infections, recent peritonitis, or significant comorbid conditions are excluded.

On the study day, each participant will receive either:

Meropenem: 0.75 g added to a 5L glucose-based peritoneal dialysis fluid (PDF) bag, or

Aztreonam: 2 g prepared similarly.

The antibiotic-containing 5L PDF bag is used as the first bag in the APD cycler session, followed by a second 5L antibiotic-free PDF bag, yielding a total of five 2L nighttime exchanges. After cycler therapy, a 1.5L Icodextrin fill is instilled for the long daytime dwell.

Sampling includes:

Venous blood: at 0 (pre-dose), 1, 2, 4.5, 6.5, 9, 10, 12, 16, and 24 hours.

Dialysate: inflow/outflow from each cycle and at defined intervals during the Icodextrin dwell (up to 24 hours).

Urine: 5 mL from a 24-hour collection in patients with residual renal function.

Drug concentrations in plasma, dialysate, and urine will be quantified using validated high-performance liquid chromatography (HPLC) techniques. Primary PK endpoints include area under the curve (AUC), maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and half-life (t½) in each compartment. Secondary endpoints include ratios of AUC and Cmax across compartments, time above the minimal inhibitory concentration (T\>MIC), and AUC0-24/MIC.

This study does not include formal hypothesis testing but aims to generate descriptive PK data to inform optimized dosing of meropenem and aztreonam for APD patients. Currently, there is a lack of pharmacokinetic data guiding IP antibiotic dosing specifically in APD. The study's findings may support more accurate and effective antibiotic administration protocols for PDAP and potentially for the treatment of other systemic infections (e.g., pneumonia) in this population.

The anticipated benefit is improved antimicrobial efficacy through better PK/PD target attainment while avoiding the need for intravenous therapy. The risk to participants is minimal, consisting primarily of standard procedures (blood draws, single-dose IP drug administration). Ethical approval has been obtained, and all participants will provide written informed consent. The study complies with Good Clinical Practice (GCP) and relevant regulatory and ethical standards, including the Declaration of Helsinki.

Detailed Description

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Conditions

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Peritoneal Dialysis Associated Peritonitis Peritoneal Dialysis (PD) Peritoneal Dialysis Peritoneal Dialysis, Continuous Ambulatory Meropenem Aztreonam Antibacterial Agents Intraperitoneal Antibiotics Kidney Failure, Chronic Anti-Bacterial Agents Drug Therapy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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intraperitoneal meropenem via cycler-therapy in APD

Intraperitoneal administration of meropenem via cycler-therapy in automated peritoneal dialysis patients without peritonitis

Group Type EXPERIMENTAL

Meropenem 1000 mg

Intervention Type DRUG

Administration of meropenem after intraperitoneal administration via cycler-therapy in APD patients without peritonitis

automated peritoneal dialysis with following long time dwell

Intervention Type OTHER

The cycler therapy, followed by a prolonged dwell, will be performed as outlined in the study protocol.

Sampling

Intervention Type DIAGNOSTIC_TEST

The sampling of blood, dialysate, and urine will be performed as outlined in the study protocol.

intraperitoneal aztreonam via cycler-therapy in APD

Intraperitoneal administration of aztreonam via cycler-therapy in automated peritoneal dialysis patients without peritonitis

Group Type EXPERIMENTAL

Aztreonam 2000 mg

Intervention Type DRUG

Administration of aztreonam after intraperitoneal administration via cycler-therapy in APD patients without peritonitis

automated peritoneal dialysis with following long time dwell

Intervention Type OTHER

The cycler therapy, followed by a prolonged dwell, will be performed as outlined in the study protocol.

Sampling

Intervention Type DIAGNOSTIC_TEST

The sampling of blood, dialysate, and urine will be performed as outlined in the study protocol.

Interventions

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Meropenem 1000 mg

Administration of meropenem after intraperitoneal administration via cycler-therapy in APD patients without peritonitis

Intervention Type DRUG

Aztreonam 2000 mg

Administration of aztreonam after intraperitoneal administration via cycler-therapy in APD patients without peritonitis

Intervention Type DRUG

automated peritoneal dialysis with following long time dwell

The cycler therapy, followed by a prolonged dwell, will be performed as outlined in the study protocol.

Intervention Type OTHER

Sampling

The sampling of blood, dialysate, and urine will be performed as outlined in the study protocol.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Male or female patients, aged over 18 years
* Patients on a stable APD regime for at least 1 month
* Patients on an APD regime using a glucose-based PDF (1,36% and/or 2,27%) for short nighttime dwells and Icodextrin for the long daytime dwell
* Willingness and ability to comply with the protocol
* Signed informed consent

Exclusion Criteria

* Any systemic infection
* Peritonitis or catheter-related infection which required antibiotic treatment within 2 months prior to the start of the study
* Allergy or hypersensitivity against study drug
* Severe hepatic impairment (Child-Pugh Class C)
* Pregnancy, or women of childbearing potential not willing to apply adequate contraception during study period
* Any disease considered relevant for proper performance of the study or risks to the patient, at the discretion of the investigator
* Hemoglobin below 9 g/dl
* BMI below 19 or above 35
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Karl Landsteiner University of Health Sciences

OTHER

Sponsor Role collaborator

Medical University of Cologne

OTHER

Sponsor Role collaborator

University Hospital St. Polten

OTHER

Sponsor Role collaborator

University of Vienna

OTHER

Sponsor Role collaborator

Karl Landsteiner Insitute for Nephrology and Haemato-Oncology

NETWORK

Sponsor Role lead

Responsible Party

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Dominik Tüchler

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martin F Wiesholzer, MD

Role: PRINCIPAL_INVESTIGATOR

UK St. Pölten

Locations

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UK St. Pölten

Sankt Pölten, , Austria

Site Status

Countries

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Austria

References

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de Vin F, Rutherford P, Faict D. Intraperitoneal administration of drugs in peritoneal dialysis patients: a review of compatibility and guidance for clinical use. Perit Dial Int. 2009 Jan-Feb;29(1):5-15.

Reference Type BACKGROUND
PMID: 19164246 (View on PubMed)

Kussmann M, Schuster L, Wrenger S, Pichler P, Reznicek G, Burgmann H, Poeppl W, Zeitlinger M, Wiesholzer M. Influence of Different Peritoneal Dialysis Fluids on the In Vitro Activity of Cefepime, Ciprofloxacin, Ertapenem, Meropenem and Tobramycin Against Escherichia Coli. Perit Dial Int. 2016 11-12;36(6):662-668. doi: 10.3747/pdi.2015.00161. Epub 2016 Sep 28.

Reference Type BACKGROUND
PMID: 27680756 (View on PubMed)

Wiesholzer M, Pichler P, Reznicek G, Wimmer M, Kussmann M, Balcke P, Burgmann H, Zeitlinger M, Poeppl W. An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2790-7. doi: 10.1128/AAC.02664-15. Print 2016 May.

Reference Type BACKGROUND
PMID: 26902765 (View on PubMed)

Warady BA, Bakkaloglu S, Newland J, Cantwell M, Verrina E, Neu A, Chadha V, Yap HK, Schaefer F. Consensus guidelines for the prevention and treatment of catheter-related infections and peritonitis in pediatric patients receiving peritoneal dialysis: 2012 update. Perit Dial Int. 2012 Jun;32 Suppl 2(Suppl 2):S32-86. doi: 10.3747/pdi.2011.00091. No abstract available.

Reference Type BACKGROUND
PMID: 22851742 (View on PubMed)

Peerapornratana S, Chariyavilaskul P, Kanjanabuch T, Praditpornsilpa K, Eiam-Ong S, Katavetin P. Short-Dwell Cycling Intraperitoneal Cefazolin Plus Ceftazidime in Peritoneal Dialysis Patients. Perit Dial Int. 2017 Mar-Apr;37(2):218-224. doi: 10.3747/pdi.2015.00300. Epub 2016 Oct 13.

Reference Type BACKGROUND
PMID: 27738089 (View on PubMed)

Manley HJ, Bailie GR. Treatment of peritonitis in APD: pharmacokinetic principles. Semin Dial. 2002 Nov-Dec;15(6):418-21. doi: 10.1046/j.1525-139x.2002.00103.x.

Reference Type BACKGROUND
PMID: 12437537 (View on PubMed)

Salzer W. Antimicrobial-resistant gram-positive bacteria in PD peritonitis and the newer antibiotics used to treat them. Perit Dial Int. 2005 Jul-Aug;25(4):313-9.

Reference Type BACKGROUND
PMID: 16022084 (View on PubMed)

Van Ende C, Tintillier M, Cuvelier C, Migali G, Pochet JM. Intraperitoneal meropenem administration: a possible alternative to the intravenous route. Perit Dial Int. 2010 Mar-Apr;30(2):250-1. doi: 10.3747/pdi.2009.00052. No abstract available.

Reference Type BACKGROUND
PMID: 20200373 (View on PubMed)

Li PK, Szeto CC, Piraino B, de Arteaga J, Fan S, Figueiredo AE, Fish DN, Goffin E, Kim YL, Salzer W, Struijk DG, Teitelbaum I, Johnson DW. ISPD Peritonitis Recommendations: 2016 Update on Prevention and Treatment. Perit Dial Int. 2016 Sep 10;36(5):481-508. doi: 10.3747/pdi.2016.00078. Epub 2016 Jun 9. No abstract available.

Reference Type BACKGROUND
PMID: 27282851 (View on PubMed)

Hsieh YP, Chang CC, Wang SC, Wen YK, Chiu PF, Yang Y. Predictors for and impact of high peritonitis rate in Taiwanese continuous ambulatory peritoneal dialysis patients. Int Urol Nephrol. 2015 Jan;47(1):183-9. doi: 10.1007/s11255-014-0763-5. Epub 2014 Jul 18.

Reference Type BACKGROUND
PMID: 25034275 (View on PubMed)

Szeto CC, Wong TY, Chow KM, Leung CB, Li PK. Are peritoneal dialysis patients with and without residual renal function equivalent for survival study? Insight from a retrospective review of the cause of death. Nephrol Dial Transplant. 2003 May;18(5):977-82. doi: 10.1093/ndt/gfg027.

Reference Type BACKGROUND
PMID: 12686674 (View on PubMed)

Perez Fontan M, Rodriguez-Carmona A, Garcia-Naveiro R, Rosales M, Villaverde P, Valdes F. Peritonitis-related mortality in patients undergoing chronic peritoneal dialysis. Perit Dial Int. 2005 May-Jun;25(3):274-84.

Reference Type BACKGROUND
PMID: 15981776 (View on PubMed)

Ghali JR, Bannister KM, Brown FG, Rosman JB, Wiggins KJ, Johnson DW, McDonald SP. Microbiology and outcomes of peritonitis in Australian peritoneal dialysis patients. Perit Dial Int. 2011 Nov-Dec;31(6):651-62. doi: 10.3747/pdi.2010.00131. Epub 2011 Jun 30.

Reference Type BACKGROUND
PMID: 21719685 (View on PubMed)

Davenport A. Peritonitis remains the major clinical complication of peritoneal dialysis: the London, UK, peritonitis audit 2002-2003. Perit Dial Int. 2009 May-Jun;29(3):297-302.

Reference Type BACKGROUND
PMID: 19458302 (View on PubMed)

Brown MC, Simpson K, Kerssens JJ, Mactier RA; Scottish Renal Registry. Peritoneal dialysis-associated peritonitis rates and outcomes in a national cohort are not improving in the post-millennium (2000-2007). Perit Dial Int. 2011 Nov-Dec;31(6):639-50. doi: 10.3747/pdi.2010.00185. Epub 2011 Jul 31.

Reference Type BACKGROUND
PMID: 21804138 (View on PubMed)

Boudville N, Kemp A, Clayton P, Lim W, Badve SV, Hawley CM, McDonald SP, Wiggins KJ, Bannister KM, Brown FG, Johnson DW. Recent peritonitis associates with mortality among patients treated with peritoneal dialysis. J Am Soc Nephrol. 2012 Aug;23(8):1398-405. doi: 10.1681/ASN.2011121135. Epub 2012 May 24.

Reference Type BACKGROUND
PMID: 22626818 (View on PubMed)

Other Identifiers

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GS1-EK-2/483-2020

Identifier Type: -

Identifier Source: org_study_id

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