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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.

Not Applicable
Conditions
Spontaneous Bacterial Peritonitis
Interventions
Registration Number
NCT04208763
Lead Sponsor
Institute of Liver and Biliary Sciences, India
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
90
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Imipenem+Tigecycline+GM-CSFGMCSF-
Imipenem+TigecyclineColistin-
Imipenem+Tigecycline+GM-CSFImipenem-
Imipenem+Tigecycline+GM-CSFTigecycline-
Imipenem+Tigecycline+GM-CSFColistin-
Imipenem+TigecyclineImipenem-
Imipenem+TigecyclineTigecycline-
Primary Outcome Measures
NameTimeMethod
Resolution of Spontaneous Bacterial peritonitis in both groupsDay 5

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

Secondary Outcome Measures
NameTimeMethod
Survival in both groupsDay 28
Development of Hepatic Encephalopathy in both groups.Day 28

Hepatic Encephalopathy will be measured as per West Haven criteria

Development of organ failures in both groups.Day 28

Organ failure will be as per APACHE score

Reversal of shock in both groupsDay 2

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

Change in ascitic fluid metabolites Nitric Oxide in both groupsDay 28

change is defined as percentage reduction in nitric oxide

Change in ascitic fluid macrophage population in both groupsDay 28

change is defined as percentage reduction in macrophage population

Development of Pneumonia in both groups.Day 28

Pneumonia will be confirmed based on imaging and clinically

Development of Acute Kidney Injury in both groupsDay 28

AKIN criteria will be used for Acute kidney injury

Resolution of Spontaneous Bacterial peritonitis in both groupsDay 2

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

Development of coagulopathy in both groups.Day 28

Coagulopathy is defined as INR \> 1.5

Trial Locations

Locations (1)

Institute of Liver and Biliary Sciences

🇮🇳

New Delhi, Delhi, India

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