| CTRI Number |
CTRI/2019/04/018349 [Registered on: 01/04/2019] Trial Registered Prospectively |
| Last Modified On: |
29/03/2019 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Other (Specify) [Plasma Exchange] |
| Study Design |
Other |
|
Public Title of Study
|
Use of plasma exchange in patients with alcoholic liver failure |
|
Scientific Title of Study
|
Efficacy and tolerability of plasma exchange in patients with alcohol related acute on chronic liver failure-a pilot study |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Rekha Hans |
| Designation |
Assistant Professor |
| Affiliation |
Postgraduate Institute of Medical Education and Research, CHANDIGARH |
| Address |
Department of Transfusion Medicine, 3rd Floor, Nehru Hospital, PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
|
| Fax |
|
| Email |
drhansrekha@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Rekha Hans |
| Designation |
Assistant Professor |
| Affiliation |
Postgraduate Institute of Medical Education and Research, CHANDIGARH |
| Address |
Department of Transfusion Medicine, 3rd Floor, Nehru Hospital, PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
|
| Fax |
|
| Email |
drhansrekha@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
SHARANYA RAMAKRISHNAN |
| Designation |
Junior Resident |
| Affiliation |
Postgraduate Institute of Medical Education and Research, CHANDIGARH |
| Address |
Department of Transfusion Medicine, 3rd Floor, Nehru Hospital, PGIMER, Chandigarh
Chandigarh
CHANDIGARH
160012
India |
| Phone |
|
| Fax |
|
| Email |
sharanya23ramki@gmail.com |
|
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Source of Monetary or Material Support
|
| Thesis Grant, PGIMER, Chandigarh |
|
|
Primary Sponsor
|
| Name |
Rekha Hans |
| Address |
Deptt. of Transfusion Medicine, 3rd Floor, Nehru Hospital, PGIMER,Chandigarh |
| Type of Sponsor |
Other [Principal Investigator] |
|
|
Details of Secondary Sponsor
|
|
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Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Sharanya Ramakrishnan |
Department of Transfusion Medicine, PGIMER Chandigarh |
3rd Floor, Nehru Hospital, PGIMER, Chandigarh
Chandigarh
CHANDIGARH |
9745365775
sharanya23ramki@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, PGIMER Chandigarh |
Approved |
|
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Regulatory Clearance Status from DCGI
|
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K704||Alcoholic hepatic failure, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Plasma Exchange Procedure with Standard Medical Treatment |
Plasma exchange shall be performed at the bedside on the enrolled patients at liver HDU (Department of Hepatology) on alternate days, using a continuous flow centrifugation plasma exchange device (Optia Spectra Terumo®, Lakewood, Colorado, USA). One to 1.5 plasma volume will be removed in a single session at a PE rate of 40ml/min with an equivalent volume replacement using group specific Fresh Frozen Plasma according to the calculated plasma volume to be replaced. Duration of each procedure will be 140-160 minutes. A total of 5 procedures will be performed on alternate days. The procedure will be performed via a peripheral vascular access using a 16 gauge needle for blood withdrawal (inlet) and return. In patients with inadequate peripheral venous access, central venous catheters (Jugular / Femoral, preferably jugular) shall be accessed to ensure uninterrupted inlet flow. |
| Comparator Agent |
Standard Medical Treatment |
All patients will be managed by standard medical management in the Dept. of Hepatology. Antibiotics will be given as per protocol and subsequently upgraded according to culture and sensitivity reports. Acute kidney injury will be managed with intravenous 20% human albumin with vasoactive agents if needed and dialysis when indicated. Patients with hepatic encephalopathy will be treated with lactulose and rifaximin. Diuretics will be given for ascites if not precluded by renal failure or hepatic encephalopathy. Ionotropes will be given for hypotension and endotracheal intubation with mechanical ventilation will be done for respiratory failure as well as for airway protection for advanced HE. All patients will receive salt restricted, high protein diet (1.5gm/kg of proteins) either enterally/parenterally in addition to thiamine and multivitamins |
|
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Age more than 18 years
2. First episode of de-compensation with APASL ACLF Research Consortium (AARC)- ACLF grade I or II (AARC score ≤10)
3. Cause of ACLF being alcohol related liver disease
4. No evidence of active infection
5. Willing to give informed consent for the procedure(In patients who are incompetent to consent,consent shall be taken from the surrogate)
|
|
| ExclusionCriteria |
| Details |
1. Pregnancy
2. Causes of ACLF other than alcohol
3. Co-existing HCC or extra-hepatic malignancy
4. Microbiological or radiological evidence of active infection
5. Active hemorrhage
6. Extra-hepatic multi-organ failure (≥3 organ failures)
7. APASL-AARC score >10
8. Known allergy to Plasma, Protamine or Heparin.
9. Mechanically ventilated patients
10. Severe preexisting cardiopulmonary disease
11. Requiring inotropic support
12. Renal failure requiring dialysis
13. Severe systemic illness like HIV
14. Post liver transplant patients
15. Death within 24 hours of presentation
|
|
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Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
1.Change in following Clinical Severity Scores
a) Maddrey’s discriminant function score (MDF) for alcoholic hepatitis
b) Model for end-stage liver disease(MELD score) and Child-Turcotte-Pugh(CTP)for alcoholic cirrhosis
c) AARC score for ACLF
d) SOF-C score(Simple Organ Failure count)
2. Clinical improvement based on LFT parameters
3. Mortality on Day 30 and Day 90
4. Duration of Hospital stay
|
Baseline, Day 10, Day 30 and Day 90
|
|
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Secondary Outcome
|
| Outcome |
TimePoints |
1. Cytokine assay:
a)IL-6& 10levels (Pre & Post plasma exchange therapy)
b)TNF-αlevel (Pre & Post plasma exchange therapy)
2. Adverse events related to Plasma exchange (Tolerability)
|
Baseline, Day 10, Day 30 and Day 90 |
|
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Target Sample Size
|
Total Sample Size="30"
Sample Size from India="30"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
03/04/2019 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="3"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
None |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
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Brief Summary
|
ACLF is a complex syndrome characterized by high
short-term mortality. Liver transplantation
is the only definitive treatment available. However,
owing to various
factors, majority of the patients are unfit for transplant.
Artificial liver support systems like plasma exchange can be used as a bridging
tool to transplant. PE by removal of accumulating toxic mediators and by
providing an improvement in biochemical and clinical parameters stabilizes the
clinical conditions related to liver failure.
Knowledge about the use of plasma exchange in acute on
chronic failure is limited. Most of the data available are retrospectively
analysed conclusions. In this study, we would prospectively analyze the
efficacy and tolerability of plasma exchange in patients with alcohol related
chronic liver disease on their first episode of decompensation. This study may
provide an evidence on the role of plasma exchange as an adjunctive modality in
treatment of these patients, helping in early intervention along the course of
the disease and thereby to better management of these patients.
We have planned a preliminary non-randomized interventional case-control pilot study. Considering the cost and limited number
of plasma exchanges that can be performed during
the specified time period, the sample size of the study has been set at 30 patients only (15
cases, 15 controls)
|