- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04437810
To Study Efficacy of Albumin in Cirrhosis With Spontaneous Bacterial Peritonitis at Low Risk for AKI Development
To Study Efficacy of Albumin in Cirrhosis With Spontaneous Bacterial Peritonitis at Low Risk for AKI Development - A Randomised Placebo Controlled Trial- A Pilot Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Aim- To compare the efficacy of albumin when compared to placebo in the development or progression of AKI in patients with cirrhosis and spontaneous bacterial peritonitis who are at low risk for AKI development (i.e Serum Bilirubin <4 mg/dL and serum creatinine < 1 mg/dl at presentation)
- Primary objective: To evaluate the Proportion of patients developing AKI by day 7
- Secondary objectives:
- To compare the resolution of SBP by day 2 and day 5 in both the groups
- To measure the Changes in PRA, TNF-α, IL-6 at day 7
- To measure the Changes in renal resistive index at day 7
- To compare Mortality by day 7 and 28 in both the groups
Methodology:
- Dose and duration of albumin/placebo infusion in both the limbs: -The dose of albumin was 1.5 g/kg of body weight given within 6 h of SBP being diagnosed over a period of 12hrs, followed by an additional infusion of 1.0 g/kg on day 3 over a period of 12 hrs. Other arm receives a similar quantity of isotonic fluid like normal saline or plasmalyte
- Renal resistive index will be done with the help of a) high frequency probe(5Mhz) together with the use of color or power Doppler to help vessel localization., sampling for RRI should be done at the level of the arcuate or interlobar arteries, adjacent to medullary pyramids. Measurements will be repeated in different parts of both organs (superior, median, and lower) when at least three reproducible waveforms have been obtained. An RRI will be calculated with the following formula: (peak systolic velocity - end diastolic velocity)/peak systolic velocity, and the mean value of three measurements at each kidney will be considered. An RRI value 0.60 ± 0.01 (mean ± SD) is usually taken as normal with a value of 0.70 being considered the upper normal threshold by most authors. In order to maximize waveform size, care will be taken in using the lowest pulse repetition frequency without aliasing, the highest possible gain without noise and the lowest wall filter. Patient will undergo RRI on day 0 and day 7.
- PRA, TNF-A and IL-6: - Measurement at day 0 and day 7 PRA is measured by generating AngI (angiotensin I) from endogenous angiotensinogen, followed by measurement by RIA of the generated AngI. Although PRA measurement is convenient for estimating the biological activity of the renin system, it may not necessarily reflect the real concentration of active renin. Il-6 is measured with the help of IL-6 ELISA kits. TNF- alpha is measured using flow cytometry.
- Antibiotics to be used in the SBP: - The gold standard treatment consists of third-generation cephalosporins, especially cefotaxime/ceftriaxone, given intravenously at a dose of 4-8 g/d for a minimum duration of 5 d. (AASLD guidelines). If patient does not respond then switch over to carbapenem (meropenem) with or without tigecycline. if patient still does not respond then GM-CSF will be given.
- Blood samples and Ascitic fluid samples will be collected and stored for measurement of Neutrophilic activity (CD66+/CD66-, CD11b) and Macrophage activity (CD 14+, CD 16+, IL-6, TNF-α)
Serum Cystatin C and Urinary NGAL, markers and predictors of renal injury will be measured in both the limbs.
Management of the complications: -
- The patients who develop sepsis (presence of SIRS; positive blood cultures); worsening of hepatic encephalopathy >2 grades, variceal bleed or deterioration of the clinical condition; worsening of AKI and volume overload will be managed according to standard protocols,
- Definitions: -
- Spontaneous bacterial peritonitis: - SBP was diagnosed when the ascitic fluid polymorphonuclear (PMN) cell count was > 250 cells/mm3.
- Resolution of Spontaneous bacterial peritonitis: - A repeat diagnostic paracentesis to document the response by a greater-than 25% decrease in ascitic fluid neutrophil count at 48 h after initiation of antibiotics is recommended
Study population: Patients with Cirrhosis of Liver who presents with Spontaneous Bacterial Peritonitis with baseline creatinine <1mg/dl and Serum Bilirubin <4mg/dl
Study Design: Single Center, Double Blinded (Patient and Treating physician), Placebo Controlled (Saline), Randomised Controlled Trial- a pilot study
Study period: 1.5 year from the date of ethics approval (2020-2022)
Sample size with justification: The study will be conducted as a pilot study and all the cases with SBP with low risk for AKI development will be recruited. The minimum number of subjects expected to be enrolled is 100.
Intervention:
- Patients in the Albumin Arm will receive Human Albumin 20% 1.5g/kg body weight (Maximum 100g) within 6 hours from the time of diagnosis over a period of 12 hours, followed by 1g/kg bodyweight (Maximum 100g) over a period of 12 hours after 48 hours of diagnosis.(D3) along with Standard medical therapy
- Patients in placebo arm will receive similar volume of isotonic fluid (saline) over same duration of time along with standard medical therapy
- Monitoring and assessment:
This RCT will be conducted at ILBS New Delhi
The following data will be recorded for each patient:
- Etiology of cirrhosis, duration, Large volume paracentesis
- H/o of jaundice, distension abdomen, swelling feet, altered sensorium, vomiting of blood or passing melena
- Height, weight and BMI
- Investigations: CBC, LFT, PT/INR, KFT.
- Disease severity (CTP and MELD scores)
- Day 0 - Hemogram, prothrombin time/ INR, KFT, LFT, TNF alpha,IL-6, PRA, ABG, blood culture, urine culture, chest X-ray, urine R/M, ascitic fluid analysis for the TLC, DLC, sugar, protein, albumin, culture, gram stain and Urine NGAL and Serum cystatin C ,Renal Resistive Index(RRI) will be done and ECG, ECHO for the volume overload, IVC diameter.
- DAY 2 - hemogram, KFT, LFT, ABG, chest X-ray, and ascitic fluid analysis for the TLC, DLC, culture, gram stain
- DAY 7: - PRA, TNF-alpha, IL-6
- DAY 7: - Renal Resistive Index,
- Day 28-- hemogram, prothrombin time/ INR, KFT, LFT
- Statistical Analysis:
- Continuous variables- Mean +/- SD
- Categorical variables as percentages (%) or Frequencies
- Student t test will be applied in continuous data compared with two groups
- Survival analysis like Cox-Regression model and Kaplan-Meir plots will be plotted to find the possible factors responsible for mortality
- Besides these, Intent to treat (ITT) and Per Protocol (PP) will be done at the time of data analysis.
Adverse effects:
- Patients receiving Albumin may experience Nausea, Vomiting, Fever with chills, dyspnea Wheezing, Volume overload, Anaphylactic reaction
- Stopping rule of study:
In Albumin arm
- Development of AKI
- Adverse reaction to drug
- Cardiopulmonary compromise
In Placebo Arm
- Development of AKI
- Development of Septic Shock
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Dr Venishetty Shantan, MD
- Phone Number: 01146300000
- Email: venishantan@gmail.com
Study Locations
-
-
Delhi
-
New Delhi, Delhi, India, 110070
- Recruiting
- Institute of Liver & Biliary Sciences
-
Contact:
- Dr Venishetty Shantan, MD
- Phone Number: 01146300000
- Email: venishantan@gmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients who are above 18 years of age
- Patients with Cirrhosis and SBP (community acquired /Health care associated/ nosocomial) with baseline Creatinine <1mg/dl, Bilirubin <4mg/dl
Exclusion Criteria:
- Antibiotic treatment within one week before the diagnosis of SBP (except for prophylactic treatment with norfloxacin)
- Significant cardiac failure, pulmonary disease
- Known Chronic Kidney Disease or findings suggestive of organic nephropathy (proteinuria, haematuria, or abnormal findings on renal USG)
- Hepatocellular carcinoma
- HIV infection;
- GI bleed within 1 month before the study
- Ileus
- Grade 3 to 4 hepatic encephalopathy
- Other types of infection
- Shock
- Serum Bilirubin ≥4 mg/dL and Serum Creatinine ≥ 1 mg/dl at presentation
- Patients requiring Albumin for any other indication.
- Presence of any potential causes of dehydration (such as diarrhea or an intense response to diuretic treatment) within one week before the diagnosis of SBP).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Albumin+ SMT
Patients in the Albumin Arm will receive Human Albumin 20% 1.5g/kg body weight (Maximum 100g) within 6 hours from the time of diagnosis over a period of 12 hours, followed by 1g/kg bodyweight (Maximum 100g) over a period of 12 hours after 48 hours of diagnosis.(D3)
along with standard medical therapy
|
- Patients in the Albumin Arm will receive Human Albumin 20% 1.5g/kg body weight (Maximum 100g) within 6 hours from the time of diagnosis over a period of 12 hours, followed by 1g/kg bodyweight (Maximum 100g) over a period of 12 hours after 48 hours of diagnosis.(D3)
standard medical therapy
|
Placebo Comparator: Placebo+SMT
- Patients in placebo arm will receive similar volume of isotonic fluid (saline) over same duration of time along with standard medical therapy
|
standard medical therapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Proportion of patients having development / progression of Acute Kidney Injury in both groups.
Time Frame: Day 7
|
Day 7
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mortality in both groups
Time Frame: Day 28
|
Day 28
|
|
Resolution of Spontaneous Bacterial Peritonitis in both groups
Time Frame: Day 2
|
Ascitic fluid absolute neutrophil count < 250
|
Day 2
|
Resolution of Spontaneous Bacterial Peritonitis in both groups
Time Frame: Day 7
|
Ascitic fluid absolute neutrophil count < 250
|
Day 7
|
Change in PRA in both groups
Time Frame: Day 7
|
Day 7
|
|
Change in TNF-alpha in both groups
Time Frame: Day 7
|
Day 7
|
|
Change in IL-6 in both groups
Time Frame: Day 7
|
Day 7
|
|
Change in Renal resistive index in both groups
Time Frame: Day 7
|
Day 7
|
|
Mortality in both groups
Time Frame: Day 7
|
Day 7
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ILBS-Cirrhosis-31
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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