<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04437810</url>
  </required_header>
  <id_info>
    <org_study_id>ILBS-Cirrhosis-31</org_study_id>
    <nct_id>NCT04437810</nct_id>
  </id_info>
  <brief_title>To Study Efficacy of Albumin in Cirrhosis With Spontaneous Bacterial Peritonitis at Low Risk for AKI Development</brief_title>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Liver and Biliary Sciences, India</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Liver and Biliary Sciences, India</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The role of Albumin in prevention and Treatment of Acute Kidney Injury (AKI) in patients with&#xD;
      Spontaneous Bacterial Peritonitis (SBP) who are at high risk of AKI development has been&#xD;
      clearly defined , which decreases the morbidity and mortality. But the role of Albumin in&#xD;
      patient with SBP who are at low risk of AKI development (Serum Bilirubin &lt;4mg/dl, Creatinine&#xD;
      &lt;1mg/dl at the time of presentation) has been controversial and there are no placebo&#xD;
      controlled trials. We propose that Albumin at the standard doses is beneficial in preventing&#xD;
      development of AKI in patients with SBP who are at low risk of AKI development.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Aim- To compare the efficacy of albumin when compared to placebo in the development or&#xD;
           progression of AKI in patients with cirrhosis and spontaneous bacterial peritonitis who&#xD;
           are at low risk for AKI development (i.e Serum Bilirubin &lt;4 mg/dL and serum creatinine &lt;&#xD;
           1 mg/dl at presentation)&#xD;
&#xD;
             -  Primary objective: To evaluate the Proportion of patients developing AKI by day 7&#xD;
&#xD;
             -  Secondary objectives:&#xD;
&#xD;
             -  To compare the resolution of SBP by day 2 and day 5 in both the groups&#xD;
&#xD;
             -  To measure the Changes in PRA, TNF-α, IL-6 at day 7&#xD;
&#xD;
             -  To measure the Changes in renal resistive index at day 7&#xD;
&#xD;
             -  To compare Mortality by day 7 and 28 in both the groups&#xD;
&#xD;
        2. Methodology:&#xD;
&#xD;
             1. Dose and duration of albumin/placebo infusion in both the limbs: -The dose of&#xD;
                albumin was 1.5 g/kg of body weight given within 6 h of SBP being diagnosed over a&#xD;
                period of 12hrs, followed by an additional infusion of 1.0 g/kg on day 3 over a&#xD;
                period of 12 hrs. Other arm receives a similar quantity of isotonic fluid like&#xD;
                normal saline or plasmalyte&#xD;
&#xD;
             2. Renal resistive index will be done with the help of a) high frequency probe(5Mhz)&#xD;
                together with the use of color or power Doppler to help vessel localization.,&#xD;
                sampling for RRI should be done at the level of the arcuate or interlobar arteries,&#xD;
                adjacent to medullary pyramids. Measurements will be repeated in different parts of&#xD;
                both organs (superior, median, and lower) when at least three reproducible&#xD;
                waveforms have been obtained. An RRI will be calculated with the following formula:&#xD;
                (peak systolic velocity - end diastolic velocity)/peak systolic velocity, and the&#xD;
                mean value of three measurements at each kidney will be considered. An RRI value&#xD;
                0.60 ± 0.01 (mean ± SD) is usually taken as normal with a value of 0.70 being&#xD;
                considered the upper normal threshold by most authors. In order to maximize&#xD;
                waveform size, care will be taken in using the lowest pulse repetition frequency&#xD;
                without aliasing, the highest possible gain without noise and the lowest wall&#xD;
                filter. Patient will undergo RRI on day 0 and day 7.&#xD;
&#xD;
             3. PRA, TNF-A and IL-6: - Measurement at day 0 and day 7 PRA is measured by generating&#xD;
                AngI (angiotensin I) from endogenous angiotensinogen, followed by measurement by&#xD;
                RIA of the generated AngI. Although PRA measurement is convenient for estimating&#xD;
                the biological activity of the renin system, it may not necessarily reflect the&#xD;
                real concentration of active renin. Il-6 is measured with the help of IL-6 ELISA&#xD;
                kits. TNF- alpha is measured using flow cytometry.&#xD;
&#xD;
             4. Antibiotics to be used in the SBP: - The gold standard treatment consists of&#xD;
                third-generation cephalosporins, especially cefotaxime/ceftriaxone, given&#xD;
                intravenously at a dose of 4-8 g/d for a minimum duration of 5 d. (AASLD&#xD;
                guidelines). If patient does not respond then switch over to carbapenem (meropenem)&#xD;
                with or without tigecycline. if patient still does not respond then GM-CSF will be&#xD;
                given.&#xD;
&#xD;
             5. Blood samples and Ascitic fluid samples will be collected and stored for&#xD;
                measurement of Neutrophilic activity (CD66+/CD66-, CD11b) and Macrophage activity&#xD;
                (CD 14+, CD 16+, IL-6, TNF-α)&#xD;
&#xD;
             6. Serum Cystatin C and Urinary NGAL, markers and predictors of renal injury will be&#xD;
                measured in both the limbs.&#xD;
&#xD;
                Management of the complications: -&#xD;
&#xD;
                  -  The patients who develop sepsis (presence of SIRS; positive blood cultures);&#xD;
                     worsening of hepatic encephalopathy &gt;2 grades, variceal bleed or deterioration&#xD;
                     of the clinical condition; worsening of AKI and volume overload will be&#xD;
                     managed according to standard protocols,&#xD;
&#xD;
                  -  Definitions: -&#xD;
&#xD;
                  -  Spontaneous bacterial peritonitis: - SBP was diagnosed when the ascitic fluid&#xD;
                     polymorphonuclear (PMN) cell count was &gt; 250 cells/mm3.&#xD;
&#xD;
                  -  Resolution of Spontaneous bacterial peritonitis: - A repeat diagnostic&#xD;
                     paracentesis to document the response by a greater-than 25% decrease in&#xD;
                     ascitic fluid neutrophil count at 48 h after initiation of antibiotics is&#xD;
                     recommended&#xD;
&#xD;
                Study population: Patients with Cirrhosis of Liver who presents with Spontaneous&#xD;
                Bacterial Peritonitis with baseline creatinine &lt;1mg/dl and Serum Bilirubin &lt;4mg/dl&#xD;
&#xD;
                Study Design: Single Center, Double Blinded (Patient and Treating physician),&#xD;
                Placebo Controlled (Saline), Randomised Controlled Trial- a pilot study&#xD;
&#xD;
                Study period: 1.5 year from the date of ethics approval (2020-2022)&#xD;
&#xD;
                Sample size with justification: The study will be conducted as a pilot study and&#xD;
                all the cases with SBP with low risk for AKI development will be recruited. The&#xD;
                minimum number of subjects expected to be enrolled is 100.&#xD;
&#xD;
                Intervention:&#xD;
&#xD;
                  -  Patients in the Albumin Arm will receive Human Albumin 20% 1.5g/kg body weight&#xD;
                     (Maximum 100g) within 6 hours from the time of diagnosis over a period of 12&#xD;
                     hours, followed by 1g/kg bodyweight (Maximum 100g) over a period of 12 hours&#xD;
                     after 48 hours of diagnosis.(D3) along with Standard medical therapy&#xD;
&#xD;
                  -  Patients in placebo arm will receive similar volume of isotonic fluid (saline)&#xD;
                     over same duration of time along with standard medical therapy&#xD;
&#xD;
                  -  Monitoring and assessment:&#xD;
&#xD;
                This RCT will be conducted at ILBS New Delhi&#xD;
&#xD;
                The following data will be recorded for each patient:&#xD;
&#xD;
                  -  Etiology of cirrhosis, duration, Large volume paracentesis&#xD;
&#xD;
                  -  H/o of jaundice, distension abdomen, swelling feet, altered sensorium,&#xD;
                     vomiting of blood or passing melena&#xD;
&#xD;
                  -  Height, weight and BMI&#xD;
&#xD;
                  -  Investigations: CBC, LFT, PT/INR, KFT.&#xD;
&#xD;
                  -  Disease severity (CTP and MELD scores)&#xD;
&#xD;
                  -  Day 0 - Hemogram, prothrombin time/ INR, KFT, LFT, TNF alpha,IL-6, PRA, ABG,&#xD;
                     blood culture, urine culture, chest X-ray, urine R/M, ascitic fluid analysis&#xD;
                     for the TLC, DLC, sugar, protein, albumin, culture, gram stain and Urine NGAL&#xD;
                     and Serum cystatin C ,Renal Resistive Index(RRI) will be done and ECG, ECHO&#xD;
                     for the volume overload, IVC diameter.&#xD;
&#xD;
                  -  DAY 2 - hemogram, KFT, LFT, ABG, chest X-ray, and ascitic fluid analysis for&#xD;
                     the TLC, DLC, culture, gram stain&#xD;
&#xD;
                  -  DAY 7: - PRA, TNF-alpha, IL-6&#xD;
&#xD;
                  -  DAY 7: - Renal Resistive Index,&#xD;
&#xD;
                  -  Day 28-- hemogram, prothrombin time/ INR, KFT, LFT&#xD;
&#xD;
                  -  Statistical Analysis:&#xD;
&#xD;
                  -  Continuous variables- Mean +/- SD&#xD;
&#xD;
                  -  Categorical variables as percentages (%) or Frequencies&#xD;
&#xD;
                  -  Student t test will be applied in continuous data compared with two groups&#xD;
&#xD;
                  -  Survival analysis like Cox-Regression model and Kaplan-Meir plots will be&#xD;
                     plotted to find the possible factors responsible for mortality&#xD;
&#xD;
                  -  Besides these, Intent to treat (ITT) and Per Protocol (PP) will be done at the&#xD;
                     time of data analysis.&#xD;
&#xD;
                Adverse effects:&#xD;
&#xD;
                  -  Patients receiving Albumin may experience Nausea, Vomiting, Fever with chills,&#xD;
                     dyspnea Wheezing, Volume overload, Anaphylactic reaction&#xD;
&#xD;
                  -  Stopping rule of study:&#xD;
&#xD;
                  -  In Albumin arm&#xD;
&#xD;
                       -  Development of AKI&#xD;
&#xD;
                       -  Adverse reaction to drug&#xD;
&#xD;
                       -  Cardiopulmonary compromise&#xD;
&#xD;
                  -  In Placebo Arm&#xD;
&#xD;
                       -  Development of AKI&#xD;
&#xD;
                       -  Development of Septic Shock&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 8, 2020</start_date>
  <completion_date type="Anticipated">April 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients having development / progression of Acute Kidney Injury in both groups.</measure>
    <time_frame>Day 7</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Resolution of Spontaneous Bacterial Peritonitis in both groups</measure>
    <time_frame>Day 2</time_frame>
    <description>Ascitic fluid absolute neutrophil count &lt; 250</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Resolution of Spontaneous Bacterial Peritonitis in both groups</measure>
    <time_frame>Day 7</time_frame>
    <description>Ascitic fluid absolute neutrophil count &lt; 250</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PRA in both groups</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in TNF-alpha in both groups</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in IL-6 in both groups</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Renal resistive index in both groups</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality in both groups</measure>
    <time_frame>Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality in both groups</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Liver Cirrhosis</condition>
  <condition>Acute Kidney Injury</condition>
  <arm_group>
    <arm_group_label>Albumin+ SMT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo+SMT</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>- Patients in placebo arm will receive similar volume of isotonic fluid (saline) over same duration of time along with standard medical therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Albumin</intervention_name>
    <description>- 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)</description>
    <arm_group_label>Albumin+ SMT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard Medical Treatment</intervention_name>
    <description>standard medical therapy</description>
    <arm_group_label>Albumin+ SMT</arm_group_label>
    <arm_group_label>Placebo+SMT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who are above 18 years of age&#xD;
&#xD;
          -  Patients with Cirrhosis and SBP (community acquired /Health care associated/&#xD;
             nosocomial) with baseline Creatinine &lt;1mg/dl, Bilirubin &lt;4mg/dl&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Antibiotic treatment within one week before the diagnosis of SBP (except for&#xD;
             prophylactic treatment with norfloxacin)&#xD;
&#xD;
          -  Significant cardiac failure, pulmonary disease&#xD;
&#xD;
          -  Known Chronic Kidney Disease or findings suggestive of organic nephropathy&#xD;
             (proteinuria, haematuria, or abnormal findings on renal USG)&#xD;
&#xD;
          -  Hepatocellular carcinoma&#xD;
&#xD;
          -  HIV infection;&#xD;
&#xD;
          -  GI bleed within 1 month before the study&#xD;
&#xD;
          -  Ileus&#xD;
&#xD;
          -  Grade 3 to 4 hepatic encephalopathy&#xD;
&#xD;
          -  Other types of infection&#xD;
&#xD;
          -  Shock&#xD;
&#xD;
          -  Serum Bilirubin ≥4 mg/dL and Serum Creatinine ≥ 1 mg/dl at presentation&#xD;
&#xD;
          -  Patients requiring Albumin for any other indication.&#xD;
&#xD;
          -  Presence of any potential causes of dehydration (such as diarrhea or an intense&#xD;
             response to diuretic treatment) within one week before the diagnosis of SBP).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Dr Venishetty Shantan, MD</last_name>
    <phone>01146300000</phone>
    <email>venishantan@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Institute of Liver &amp; Biliary Sciences</name>
      <address>
        <city>New Delhi</city>
        <state>Delhi</state>
        <zip>110070</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr Venishetty Shantan, MD</last_name>
      <phone>01146300000</phone>
      <email>venishantan@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>January 27, 2022</last_update_submitted>
  <last_update_submitted_qc>January 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peritonitis</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Acute Kidney Injury</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04437810
org study id: ILBS-Cirrhosis-31
nct id: NCT04437810
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The role of Albumin in prevention and Treatment of Acute Kidney Injury (AKI) in patients with
      Spontaneous Bacterial Peritonitis (SBP) who are at high risk of AKI development has been
      clearly defined , which decreases the morbidity and mortality. But the role of Albumin in
      patient with SBP who are at low risk of AKI development (Serum Bilirubin <4mg/dl, Creatinine
      <1mg/dl at the time of presentation) has been controversial and there are no placebo
      controlled trials. We propose that Albumin at the standard doses is beneficial in preventing
      development of AKI in patients with SBP who are at low risk of AKI development.
1. 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

        2. Methodology:

             1. 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

             2. 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.

             3. 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.

             4. 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.

             5. 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)

             6. 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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Proportion of patients having development / progression of Acute Kidney Injury in both groups.
time frame: Day 7
measure: Resolution of Spontaneous Bacterial Peritonitis in both groups
time frame: Day 2
description: Ascitic fluid absolute neutrophil count < 250
measure: Resolution of Spontaneous Bacterial Peritonitis in both groups
time frame: Day 7
description: Ascitic fluid absolute neutrophil count < 250
measure: Change in PRA in both groups
time frame: Day 7
measure: Change in TNF-alpha in both groups
time frame: Day 7
measure: Change in IL-6 in both groups
time frame: Day 7
measure: Change in Renal resistive index in both groups
time frame: Day 7
measure: Mortality in both groups
time frame: Day 7
measure: Mortality in both groups
time frame: Day 28
arm group label: Albumin+ SMT
arm group type: Experimental
description: 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
arm group label: Placebo+SMT
arm group type: Placebo Comparator
description: - Patients in placebo arm will receive similar volume of isotonic fluid (saline) over same duration of time along with standard medical therapy
intervention type: Biological
intervention name: Albumin
description: - 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)
arm group label: Albumin+ SMT
intervention type: Other
intervention name: Standard Medical Treatment
description: standard medical therapy
arm group label: Albumin+ SMT
arm group label: Placebo+SMT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dr Venishetty Shantan, MD
phone: 01146300000
email: venishantan@gmail.com
facility: 
status: Recruiting
contact: 
country: India
responsible party type: Sponsor
mesh term: Peritonitis
mesh term: Liver Cirrhosis
mesh term: Acute Kidney Injury
mesh term: Fibrosis
sharing ipd: Undecided