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

NCT ID: NCT06818565

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-10
• Study Completion Date: 2026-12-31

Brief Summary

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.

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.

Conditions

Acute-On-Chronic Liver Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Meropenem

Meropenem 2gm TDS over 3 hours infusion Teicoplanin 400 mg iv BD for 3 doses f/b 400 mg iv OD

Group Type: ACTIVE_COMPARATOR

Meropenem Injection

Intervention Type: DRUG

Meropenem 2 gm iv TDS

Teicoplanin

Intervention Type: DRUG

Teicoplanin 400 mg iv BD 3 doses followed by 400mg iv OD

Ceftazidime avibactam

Ceftazidime avibactam 2.5 gm iv TDS. Teicoplanin 400 mg iv BD for 3 doses f/b 400 mg iv OD

Group Type: EXPERIMENTAL

Ceftazidime-avibactam

Intervention Type: DRUG

Ceftazidime-avibactam 2.5 gm iv TDS

Teicoplanin

Intervention Type: DRUG

Teicoplanin 400 mg iv BD 3 doses followed by 400mg iv OD

Interventions

Meropenem Injection

Meropenem 2 gm iv TDS

Intervention Type: DRUG

Ceftazidime-avibactam

Ceftazidime-avibactam 2.5 gm iv TDS

Intervention Type: DRUG

Teicoplanin

Teicoplanin 400 mg iv BD 3 doses followed by 400mg iv OD

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Liver and Biliary Sciences, India

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institute of Liver & Biliary Sciences (ILBS)

New Delhi, National Capital Territory of Delhi, India

Countries

India

Central Contacts

Dr Amanjot Kaur, MD

Role: CONTACT

amanjotbahri@gmail.com

01146300000

Prof. Rakhi Maiwall, DM

Role: CONTACT

rakhi_2011@yahoo.co.in

01146300000

Facility Contacts

Dr Amanjot Kaur, MD

Role: primary

amanjotbahri@gmail.com

01146300000

Other Identifiers

ILBS-ACLF-20

Identifier Type: -

Identifier Source: org_study_id