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Plasma Exchange in Acute on Chronic Liver Failure (PLEXAR)

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ClinicalTrials.gov Identifier: NCT04051437
Recruitment Status : Not yet recruiting
First Posted : August 9, 2019
Last Update Posted : August 9, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. Pramod Kumar, Asian Institute of Gastroenterology, India

Brief Summary:
Acute on chronic liver failure (ACLF) is a distinct syndrome in patients with chronic liver disease with rapid clinical deterioration and has high short term mortality within one month.Despite aggressive clinical care, only half of the patients could survive an episode of ACLF. The investigators hypothesized that the early treatment with therapeutic plasma exchange with plasma and albumin in ACLF patients might improve overall survival in carefully selected patients by removing cytokines, chemokines and toxic substances.

Condition or disease Intervention/treatment Phase
Cirrhosis, Liver Acute-On-Chronic Liver Failure Procedure: Plasma exchange Drug: Standard medical treatment Phase 3

Detailed Description:

Acute on chronic liver failure (ACLF) lacks a consensus definition and definitive management approaches. The various management strategies include treatment of acute insult, support of multiple organ systems and disease-specific medications such as antivirals for hepatitis B, steroids for alcoholic hepatitis, and autoimmune hepatitis. Despite aggressive clinical care, only half of the patients could survive an episode of ACLF. ACLF is a dynamic condition and has specific time-related disease course. Majority of patients of the patients attain their final grade of ACLF between 3 rd and 7th day and makes it an ideal time to assess the prognosis. Recently, liver transplantation option also explored in patients not responding to standard medical care and appeared promising. Early liver transplantation is considered if the baseline model for end-stage liver disease (MELD) score > 28, Asia pacific association for the study of the liver (APASL) ACLF Research Consortium (AARC) score of > 10, advanced hepatic encephalopathy in the absence of organ failures or overt sepsis. However, liver transplantation is feasible only in 25% cases and approximately 67% waitlist mortality. Treating ACLF patients early in the disease course, i.e., window period, may prevent multiorgan dysfunction and improve outcomes. Therefore, these alternative modalities can act as bridging to liver transplantation and hasten the spontaneous liver regeneration and hence, transplant-free recovery in some patients.

Plasma exchange has been shown to reduce cytokines, inflammatory mediators, and damage-associated molecular patterns. The early experience of therapeutic plasma exchange in patients with hepatitis B ACLF shows a survival benefit compared to standard of care. Changes in albumin quantity and quality are noted in patients with cirrhosis. An increase in oxidized albumin, ischemia-modified albumin, and albumin dimerization is observed ACLF patients and changes are more pronounced compared to cirrhotic patients. These changes are well correlated with short and long term mortality.

Hence the investigators hypothesized that the early treatment with therapeutic plasma exchange with plasma and albumin in ACLF patients improves overall survival in carefully selected patients.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Therapeutic Plasma Exchange in Patients With Acute on Chronic Liver Failure: A Randomized Controlled Trial (PLEXAR)
Estimated Study Start Date : August 15, 2019
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Plasma exchange
The consented patients will receive standard medical management with sessions of single volume plasma exchange with fresh frozen plasma and 5% human albumin.Plasma exchange session will be done on an alternate day to a maximum of 5 procedures.
Procedure: Plasma exchange
During each plasma exchange session 3-4lt (1.2-1.3 times of plasma volume) of plasma will be exchanged with fresh frozen plasma and 5% albumin. Plasma exchange session will be done on an alternate day to a maximum of 5 procedures. PLEX will be discontinued if the patients Shows sustained clinical improvement, Receive liver transplantation, Refuses further PLEX session No improvement in clinical condition Intolerant to PLEX procedure

Active Comparator: Standard medical treatment
The consented patients will receive standard medical treatment which includes adequate nutrition (35-45 Kcal/Kg with 1.5gm/Kg protein) diuretics, anti HE measures, appropriate antibiotics for infections, entecavir 0.5 mg once daily for hepatitis B, and steroids for autoimmune hepatitis.
Drug: Standard medical treatment
The consented patients will receive standard medical treatment which includes adequate nutrition (35-45 Kcal/Kg with 1.5gm/Kg protein) diuretics, anti HE measures, appropriate antibiotics for infections,tablet entecavir 0.5 mg once daily for hepatitis B, and steroids for autoimmune hepatitis.




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 90 days ]

Secondary Outcome Measures :
  1. Transplant free survival [ Time Frame: 90 days ]
  2. Development of organ dysfunction [ Time Frame: 28 days ]
  3. Development of cirrhosis complications [ Time Frame: 28 days ]
  4. Improvement in Model for end stage liver disease score [ Time Frame: 90 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients diagnosed with ACLF as per APASL criteria with AARC score of ≥8

Exclusion Criteria:

  1. Uncontrolled sepsis
  2. Septic shock requiring inotropes despite fluid resuscitation
  3. Active or recent bleeding (unless controlled for >48 hours).
  4. Severe thrombocytopenia (≤20×10^9/L)
  5. Acute kidney injury with Creatinine > 2 or the need of RRT
  6. Respiratory failure (Severe ARDS)
  7. Chronic kidney disease
  8. Hepatocellular carcinoma outside Milan criteria (1 nodule ≤5 cm or 3 nodules ≤3 cm)
  9. HIV infection
  10. Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04051437


Contacts
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Contact: Pramod Kumar, MD +91-9814933544 dapramod@gmail.com

Sponsors and Collaborators
Asian Institute of Gastroenterology, India

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Responsible Party: Dr. Pramod Kumar, Principal Investigator, Asian Institute of Gastroenterology, India
ClinicalTrials.gov Identifier: NCT04051437     History of Changes
Other Study ID Numbers: AIG/IEC34/07.2019-08
First Posted: August 9, 2019    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Dr. Pramod Kumar, Asian Institute of Gastroenterology, India:
Plasma exchange
Acute on chronic liver failure

Additional relevant MeSH terms:
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Liver Failure
Hepatic Insufficiency
End Stage Liver Disease
Acute-On-Chronic Liver Failure
Liver Cirrhosis
Liver Diseases
Digestive System Diseases
Liver Failure, Acute