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
|Condition or disease||Intervention/treatment||Phase|
|Cirrhosis, Liver Acute-On-Chronic Liver Failure||Procedure: Plasma exchange Drug: Standard medical treatment||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||130 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
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.
- Overall Survival [ Time Frame: 90 days ]
- Transplant free survival [ Time Frame: 90 days ]
- Development of organ dysfunction [ Time Frame: 28 days ]
- Development of cirrhosis complications [ Time Frame: 28 days ]
- Improvement in Model for end stage liver disease score [ Time Frame: 90 days ]
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
|Contact: Pramod Kumar, MDfirstname.lastname@example.org|