Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT04051437
Other study ID # AIG/IEC34/07.2019-08
Secondary ID
Status Not yet recruiting
Phase Phase 3
First received
Last updated
Start date August 15, 2019
Est. completion date March 31, 2020

Study information

Verified date August 2019
Source Asian Institute of Gastroenterology, India
Contact Pramod Kumar, MD
Phone +91-9814933544
Email dapramod@gmail.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 130
Est. completion date March 31, 2020
Est. primary completion date March 31, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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

Study Design


Intervention

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
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.

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Asian Institute of Gastroenterology, India

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Survival 90 days
Secondary Transplant free survival 90 days
Secondary Development of organ dysfunction 28 days
Secondary Development of cirrhosis complications 28 days
Secondary Improvement in Model for end stage liver disease score 90 days
See also
  Status Clinical Trial Phase
Recruiting NCT05793983 - S100A8/A9 and Innate Immunity in Liver Disease
Completed NCT04604860 - Use of EL-FIT App to Promote Physical Activity N/A
Recruiting NCT05928624 - A Pilot Trial to Test the Feasibility of Utilizing Home Blood Pressure Monitoring to Optimize the Administration of Midodrine Among Decompensated Cirrhosis Patients N/A
Active, not recruiting NCT01438970 - Effects of Treatment of Ascites by the ALFApump System on Renal and Circulatory Function Phase 2
Recruiting NCT05998330 - LiverPAL: A Trial of Inpatient Palliative Care for Patients With Advanced Liver Disease N/A
Completed NCT04581369 - Cirrhosis Medical Home N/A
Withdrawn NCT04244877 - Rifaximin's Effect on Covert Hepatic Encephalopathy With SIBO and Gastrointestinal Dysmotility Phase 3
Recruiting NCT04588077 - Comparison Between 2-dose Versus 3-dose Regimens of Heplisav B in Cirrhosis Phase 4
Recruiting NCT05538962 - Longitudinal Monitoring of Inflammation in Cirrhosis N/A
Completed NCT04082780 - Rifamycin in Minimal Hepatic Encephalopathy Phase 2
Completed NCT03850977 - Is There an Association Between Chronic Pancreatitis and Pulmonary Function
Active, not recruiting NCT03736265 - Carvedilol for Prevention of Esophageal Varices Progression N/A
Recruiting NCT04530760 - Intraabdominal Hypertension and Occurrence of Microaspiration in Cirrhotics Under Mechanical Ventilation
Recruiting NCT05093218 - Effect of Branch Chain Amino Acid Therapy on Sarcopenia in Children With Chronic Liver Disease. N/A
Recruiting NCT03437876 - Study on Effect of Intestinal Microbiota Transplantation in Hepatitis B Virus Induced Cirrhosis N/A
Recruiting NCT05604274 - Longitudinal Monitoring of Stool Characteristics
Recruiting NCT04867954 - Development of 4D Flow MRI for Risk Stratification of Variceal Bleeding in Cirrhosis
Completed NCT04643795 - Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Multiple Oral Doses of MGL-3196 in Subjects With Varying Degrees of Hepatic Impairment and Healthy Matched Control Subjects Phase 1
Active, not recruiting NCT02344680 - Liver Fibrosis in Zambian HIV-HBV Co-infected Patients
Completed NCT04121520 - Perioperative Care of HVPG Measurement (CHESS1904): An International Multicenter Survey