Comparison of Efficacy and Safety of Ceftazidime Avibactam Versus Extended Infusions of High Dose Meropenem in Patients of ACLF With Nosocomial Infections.

Acute on chronic liver failure patients are at high risk for nosocomial infections due to liver dysfunction, which impairs immune responses and increases vulnerability to infections. Key factors contributing to nosocomial infections in ACLF patients include ascites, use of invasive devices, and recent hospitalization, frequent need for broad spectrum antibiotics. Multidrug resistance is a growing issue, making treatment more challenging, common pathogens involved are gram negative bacteria such as Escherichia Coli and Klebsiella pneumoniae. Surveillance data show increasing carbapenem resistant enterobacterales (CRE) infection rates in cirrhotics, with high morbidity and mortality rates. The impact of these nosocomial infections is profound, significantly worsen outcomes in ACLF patients, leading to prolonged hospitalizations, increased health care costs and higher mortality rates. Early detection and effective antibiotic stewardship are essential to manage antibiotic resistance and improve patient outcomes. In this study we aim to compare efficacy and safety of Ceftazidime avibactam versus extended infusions of high dose Meropenem in patients of ACLF with nosocomial infections.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute-On-Chronic Liver Failure
• Intervention / Treatment: Drug: Meropenem Injection; Drug: Teicoplanin; Drug: Ceftazidime-avibactam

Detailed Description

Hypothesis - We hypothesize that ceftazidime-avibactum would be superior and an effective carbapenem sparing agent compared to extended high dose carbapenems as empirical therapy in management of nosocomial infections caused by carbapenem resistant organisms in patients with ACLF.

Aim -To compare the efficacy and safety of Ceftazidime avibactam and extended infusions of high dose Meropenem as emperical antibiotic in patients of ACLF with nosocomial infections caused by carbapenem resistant organisms.

Primary objective:

• To compare the efficacy of Ceftazidime avibactam over extended infusions of high dose carabapenem as emperical antibiotic in achieving clinical response at day 3 in patients of ACLF with suspected nosocomial infections.

Secondary objectives:

• To study the spectrum of nosocomial infections, bacterial DNA and resistance genes in the context of nosocomial infections in ACLF
• Proportion of patients requiring escalation/de-escalation of antibiotics at day 3
• Incidence of clinical and microbiologic response at day 5 and day 7
• Time to escalation of antibiotics in both groups
• Transfer to icu, mortality, and progression of organ failures and worsening of AARC scores by grade I, SOFA score by point 2.
• Microbiologic outcome (Eradication/Persistence)
• To identify biomarkers of host response to empirical antibiotic regimen
• Transplant free survival at day 15 and day 28
• Proportion of patients made eligible for transplant day 7. A prospective, Randomized Control Trial. Single centre, Open label, Block randomization will be done, it will be implemented by IWRS method. This study will be conducted in Department of Hepatology, ILBS.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Amanjot Kaur, MD; Phone Number: 01146300000; Email: amanjotbahri@gmail.com
• Study Contact Backup: Name: Prof. Rakhi Maiwall, DM; Phone Number: 01146300000; Email: rakhi_2011@yahoo.co.in

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences (ILBS)
      • Contact: Dr Amanjot Kaur, MD; Phone Number: 01146300000; Email: amanjotbahri@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. ACLF as per APASL criteria
3. ACLF patients with nosocomial infections caused by carbapenem resistant organism (defined as suspected or documented evidence of infection after 48 hours of hospitalization) requiring antibiotics.

Exclusion Criteria:

1. Severe septic shock with MOF requiring escalation of antibiotics
2. Patients having known allergies to meropenem or Ceftazidime Avibactam
3. Culture sensitivity showing isolate non susceptible to study drug being investigated.
4. Already on either regimen, receiving meropenem or Ceftazidime Avibactam >48 hours.
5. On mechanical ventilator support PF ratio < 300.
6. Patients on immunosuppression medication
7. HCC or other malignancies
8. CKD
9. CAD
10. Pregnancy or Lactation
11. Post Liver Transplantation
12. Refusal to consent
13. PLWHA

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
Active Comparator: Meropenem; Meropenem 2gm TDS over 3 hours infusion Teicoplanin 400 mg iv BD for 3 doses f/b 400 mg iv OD	Drug: Meropenem Injection; Meropenem 2 gm iv TDS; Drug: Teicoplanin; Teicoplanin 400 mg iv BD 3 doses followed by 400mg iv OD
Experimental: Ceftazidime avibactam; Ceftazidime avibactam 2.5 gm iv TDS. Teicoplanin 400 mg iv BD for 3 doses f/b 400 mg iv OD	Drug: Teicoplanin; Teicoplanin 400 mg iv BD 3 doses followed by 400mg iv OD; Drug: Ceftazidime-avibactam; Ceftazidime-avibactam 2.5 gm iv TDS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of ACLF patients with nosocomial infection by carbapenem resistant organisms showing clinical response at the end of treatment.	Day 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to escalation or descalation of antibiotics	within 3 days
Progression in terms of organ dysfunction/failure at day 5 and 7.	day 5 and 7
Incidence of adverse events in both groups.	within 7 to 10 days
Duration of hospital and ICU stay	day 28
Mortality at day 15 and day 28	day 15 & 28

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): February 10, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 1, 2025
• First Submitted That Met QC Criteria: February 7, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Digestive System Diseases; Liver Diseases; Hepatic Insufficiency; Iatrogenic Disease; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Cross Infection; Acute-On-Chronic Liver Failure; Third Generation Cephalosporins; Beta Lactam Antibiotics; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; beta-Lactamase Inhibitors; Meropenem; Avibactam, ceftazidime drug combination; Teicoplanin; Avibactam; Ceftazidime
• Other Study ID Numbers: ILBS-ACLF-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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