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.

Sponsor
Institute of Liver and Biliary Sciences, India (Other)
Overall Status
Recruiting
CT.gov ID
NCT04208763
Collaborator
(none)
90
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2
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Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
N/A

Study Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Imipenem and Tigecycline Versus Imipenem and Tigecycline With GM-CSF for the Management of Spontaneous Bacterial Peritonitis Presenting With Septic Shock.
Actual Study Start Date :
Dec 20, 2019
Anticipated Primary Completion Date :
Dec 31, 2021
Anticipated Study Completion Date :
Dec 31, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Resolution of Spontaneous Bacterial peritonitis in both groups [Day 5]

    Response is defined by resolution of SBP in terms of total counts < 500,Neutrophil<250

Secondary Outcome Measures

  1. Reversal of shock in both groups [Day 2]

    Blood pressure more than 90/60 mmHg with no inotropes requirement

  2. Survival in both groups [Day 7]

  3. Survival in both groups [Day 28]

  4. Change in ascitic fluid metabolites Nitric Oxide in both groups [Day 28]

    change is defined as percentage reduction in nitric oxide

  5. Change in ascitic fluid macrophage population in both groups [Day 28]

    change is defined as percentage reduction in macrophage population

  6. Development of Hepatic Encephalopathy in both groups. [Day 28]

    Hepatic Encephalopathy will be measured as per West Haven criteria

  7. Development of Acute Kidney Injury in both groups [Day 28]

    AKIN criteria will be used for Acute kidney injury

  8. Development of Pneumonia in both groups. [Day 28]

    Pneumonia will be confirmed based on imaging and clinically

  9. Development of organ failures in both groups. [Day 28]

    Organ failure will be as per APACHE score

  10. Development of coagulopathy in both groups. [Day 28]

    Coagulopathy is defined as INR > 1.5

  11. Resolution of Spontaneous Bacterial peritonitis in both groups [Day 2]

    Response is defined by resolution of SBP in terms of total counts < 500,Neutrophil<250

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Institute of Liver and Biliary Sciences New Delhi Delhi India 110070

Sponsors and Collaborators

  • Institute of Liver and Biliary Sciences, India

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Institute of Liver and Biliary Sciences, India
ClinicalTrials.gov Identifier:
NCT04208763
Other Study ID Numbers:
  • ILBS-SBP-02
First Posted:
Dec 23, 2019
Last Update Posted:
Feb 16, 2021
Last Verified:
Feb 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 16, 2021