A Randomized Controlled Trial Comparing Imipenem and Tigecycline Versus Imipenem and Tigecycline With GM-CSF for the Management of Spontaneous Bacterial Peritonitis Presenting With Septic Shock.

Imipenem and Tigecycline Versus Imipenem and Tigecycline With GM-CSF for the Management of Spontaneous Bacterial Peritonitis Presenting With Septic Shock.

Study population: A total of 90 consecutive patients of decompensated cirrhosis of any etiology, presenting to the Institute of Liver and Biliary Sciences with SBP with septic shock will be included.

Study design: Randomized controlled trial Study period: August 2019 to December 2021. Sample size: Assuming that the response rate is 90% with GM-CSF and 60% without GM-CSF after day 5. With alpha 5 and power 80,we need to enroll 76 cases (38 cases with each). Further assuming 20 % drop-out due to various reasons, it was decided to enroll 90 cases randomly allocated into two groups (i.e., 45 in each) by block randomization method by taking block size as 6. So for the present study, it was decided to enroll 90 cases in all.

Group A will be given Imipenem and Tigecycline. Patients with recent hospitalisation will be given Colistin in addition.

Group B will be given: To another group we will give Imipenem and Tigecycline and GMCSF.Patients with recent hospitalisation will be given Colistin in addition.

The dose of antibiotic will be given at dosage Inj Imipenem 1gm i.v. TDS Inj Tigecycline 100mg stat f/b 50mg i.v. OD Inj GM-CSF 500mcg s.c. OD Inj Colistin 9 MIU i.v. stat f/b 4.5 MIU i.v. BD Monitoring and assessment At the baseline, all patients will undergo investigational evaluation as described

Daily monitoring of following parameters:

• Haemoglobin,
• Total peripheral leucocyte counts,
• Platelet counts,
• Renal function tests
• Liver function tests and
• Chest X rays will be undertaken
• Ascitic fluid analysis will be done on day 0, day 2 and day 5

Stopping rule:If the patient develops a TLC of more than 50,000, the dose of the GM CSF will be reduced to half and the treatment continued. If, even after the reduction, the TLC rises to more than 50,000, then the treatment will be stopped and the patient excluded.

Expected outcome of the project: Addition of GM-CSF to standard antibiotic regimen helps resolve SBP and improves outcome in decompensated liver cirrhotic patients.

Study Overview

• Status: Recruiting
• Conditions: Spontaneous Bacterial Peritonitis
• Intervention / Treatment: Drug: Imipenem; Drug: Tigecycline; Drug: GMCSF; Drug: Colistin

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Abhijeet Ranjan, MD; Phone Number: 01146300000; Email: drkmrabhijeet@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Recruiting
      • Institute of Liver and Biliary Sciences
      • Contact: Dr Abhijeet Ranjan, MD; Phone Number: 01146300000; Email: drkmrabhijeet@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Spontaneous Bacterial Peritonitis (SBP) with shock in a cirrhotic
2. Hospital acquired SBP with shock
3. Difficult to treat SBP

Exclusion Criteria:

1. Refractory Shock
2. Cardiac comorbidities (known Coronary Artery Disease)
3. Chronic Kidney Disease on Maintenance Hemodialysis
4. < 18 years.
5. Advanced Hepatocellular Carcinoma
6. Post liver transplant
7. HIV + ve, Immunosuppressive therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imipenem+Tigecycline+GM-CSF	Drug: Imipenem; Inj Imipenem 1gm i.v. TDS; Drug: Tigecycline; Inj Tigecycline 100mg stat f/b 50mg i.v. OD; Drug: GMCSF; Inj GM-CSF 500mcg s.c. OD; Drug: Colistin; Inj Colistin 9 MIU i.v. stat f/b 4.5 MIU i.v. BD
Active Comparator: Imipenem+Tigecycline	Drug: Imipenem; Inj Imipenem 1gm i.v. TDS; Drug: Tigecycline; Inj Tigecycline 100mg stat f/b 50mg i.v. OD; Drug: Colistin; Inj Colistin 9 MIU i.v. stat f/b 4.5 MIU i.v. BD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of Spontaneous Bacterial peritonitis in both groups	Response is defined by resolution of SBP in terms of total counts < 500,Neutrophil<250	Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reversal of shock in both groups	Blood pressure more than 90/60 mmHg with no inotropes requirement	Day 2
Survival in both groups		Day 7
Survival in both groups		Day 28
Change in ascitic fluid metabolites Nitric Oxide in both groups	change is defined as percentage reduction in nitric oxide	Day 28
Change in ascitic fluid macrophage population in both groups	change is defined as percentage reduction in macrophage population	Day 28
Development of Hepatic Encephalopathy in both groups.	Hepatic Encephalopathy will be measured as per West Haven criteria	Day 28
Development of Acute Kidney Injury in both groups	AKIN criteria will be used for Acute kidney injury	Day 28
Development of Pneumonia in both groups.	Pneumonia will be confirmed based on imaging and clinically	Day 28
Development of organ failures in both groups.	Organ failure will be as per APACHE score	Day 28
Development of coagulopathy in both groups.	Coagulopathy is defined as INR > 1.5	Day 28
Resolution of Spontaneous Bacterial peritonitis in both groups	Response is defined by resolution of SBP in terms of total counts < 500,Neutrophil<250	Day 2

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2019
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (Actual): December 23, 2019

Study Record Updates

• Last Update Posted (Actual): February 16, 2021
• Last Update Submitted That Met QC Criteria: February 14, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Imipenem; Tigecycline; Colistin
• Other Study ID Numbers: ILBS-SBP-02

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