Clinical trial NCT04208763: 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.
Official title: Imipenem and Tigecycline Versus Imipenem and Tigecycline With GM-CSF for the Management of Spontaneous Bacterial Peritonitis Presenting With Septic Shock.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Spontaneous Bacterial Peritonitis
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2019-12-23
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Resolution of Spontaneous Bacterial peritonitis in both groups
timeFrame: Day 5
Secondary outcomes:
measure: Reversal of shock in both groups
timeFrame: Day 2
measure: Survival in both groups
timeFrame: Day 7
measure: Survival in both groups
timeFrame: Day 28
measure: Change in ascitic fluid metabolites Nitric Oxide in both groups
timeFrame: Day 28
measure: Change in ascitic fluid macrophage population in both groups
timeFrame: Day 28
measure: Development of Hepatic Encephalopathy in both groups.
timeFrame: Day 28
measure: Development of Acute Kidney Injury in both groups
timeFrame: Day 28
measure: Development of Pneumonia in both groups.
timeFrame: Day 28
measure: Development of organ failures in both groups.
timeFrame: Day 28
measure: Development of coagulopathy in both groups.
timeFrame: Day 28
measure: Resolution of Spontaneous Bacterial peritonitis in both groups
timeFrame: Day 2
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver and Biliary Sciences
state: Delhi
Study officials:
References: