| CTRI Number |
CTRI/2022/01/039094 [Registered on: 03/01/2022] Trial Registered Prospectively |
| Last Modified On: |
18/03/2025 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Biological |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A study to determine if a new therapy(Plasma Exchange) can help in recovery of Acute on chronic Liver failure. |
Scientific Title of Study
Modification(s)
|
Plasma Exchange in Acute on chronic Liver Failure: A Randomized Control Trial. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Shalimar |
| Designation |
Additional Professor |
| Affiliation |
All India Institute of Medical Sciences |
| Address |
Room No. 127, Ist floor, Old OT Block, Department of Gastroenterology & Human Nutrition Unit
All India Institute of Medical Sciences, Ansari Nagar
South
DELHI
110029
India |
| Phone |
9868397211 |
| Fax |
|
| Email |
drshalimar@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Shekhar Swaroop |
| Designation |
Senior Resident |
| Affiliation |
All India Institute of Medical Sciences |
| Address |
Department of Gastroenterology All India Institute of Medical Sciences
Ansari Nagar
South
DELHI
110029
India |
| Phone |
9113139210 |
| Fax |
|
| Email |
s.swaroop123456@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Shekhar Swaroop |
| Designation |
Senior Resident |
| Affiliation |
All India Institute of Medical Sciences |
| Address |
Department of Gastroenterology All India Institute of Medical Sciences
Ansari Nagar
South
DELHI
110029
India |
| Phone |
9113139210 |
| Fax |
|
| Email |
s.swaroop123456@gmail.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
All India Institute of Medical Sciences |
| Address |
Department of Gastroenterology & Human Nutrition Unit, AIIMS, Delhi |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Shalimar |
All India Institute of Medical Sciences |
Department of Gastroenterology & Human Nutrition Unit, AIIMS
South
DELHI |
9868397211
drshalimar@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| Institute Ethics Committee |
Approved |
| Institute Ethics committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K720||Acute and subacute hepatic failure, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Comparator Agent |
Standard medical management |
A uniform protocol will be followed after hospitalization. Antibiotics will be given to those who develop an infection after inclusion- after collection of blood, urine, and ascitic fluid for culture - and later will be modified as per sensitivity reports. Patients who developed Spontaneous Bacterial Peritonitis (SBP) and hepatorenal syndrome (HRS) will be managed as per recommendations. Renal replacement therapy (RRT) and ventilator support will be provided when appropriate. Appropriate treatment for hepatic encephalopathy will be instituted- lactulose, rifaximin or l-ornithine l-aspartate (LOLA). Inotropes to maintain mean arterial blood pressure above 60 mmHg. All patients will receive enteral/parenteral feeds with 2,500 kcal and 1.5 g/kg of proteins. Steroids will be given as indicated. |
| Intervention |
Therapeutic Plasma Exchange |
The replacement will be done by using the combination of 1/3rd albumin/Normal saline+ 2/3rd plasma (FFP) where albumin used is 5%W/V (if 20% albumin is used it will be diluted or reconstituted in normal saline). The total volume removed will be 1-1.5 times the plasma volume. Plasma volume will be calculated using Nadler’s formula. The fluid balance will be kept between 90-110% depending on the pre-procedural hemodynamic status of the patient. The removal rate is 60-150 ml/hr. |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Both |
| Details |
1. Written informed consent.
2. 18 – 60 years of age
3. EASL-ACLF grade 1, 2 and 3 |
|
| ExclusionCriteria |
| Details |
1. Systolic blood pressure < 90 mm Hg
2. Lack of informed consent
3. Coexisting severe illness e.g., coronary artery disease, malignancy etc
4. Post Liver Transplant patients
5. Pregnancy
7. Active infection- bacterial or fungal.
8. Hepatocellular carcinoma
9. Patient who dies within 48 hrs of admission
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To study the effect of Plasma Exchange (PE) on 28-day mortality in patients with ACLF. |
28 days |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1) To study the effect of PE on APASAL ACLF Research Consortium (AARC) score, CLIF-C ACLF score, Acute Physiology and Chronic Health Evaluation (APACHE) II, and Systemic Inflammatory Response Syndrome (SIRS).
2) To study the effect of PE on the resolution or development of organ failures in ACLF.
3) To study the effect of plasma exchange on cytokine profile which includes pro-inflammatory cytokines (INF-A2, INF-G, IL-12, IL-15, IL-17, MCP-3, IL-6, MCP-1, MIP -1A, MIP-1B, TNF-A, TNF-B, IL-8, RNTS, IP – 10, ETXN), anti-inflammatory cytokines (IL-2, IL-4, IL-5, IL-10, IL-1RA, IL-7), growth factors (EGF, FGF-2, TGF A, G-CSF, GM-CSF, PDGF), DAMPS (HMGB1), endotoxin in ACLF.
4) To study the incidence of infections and other complications in ACLF patients undergoing plasma exchange |
1) 28 days
2) 28 days
3) 28 days
4) 28 days
|
|
Target Sample Size
Modification(s)
|
Total Sample Size="194"
Sample Size from India="194"
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 2 |
|
Date of First Enrollment (India)
|
03/01/2022 |
| 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="2"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
NA |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
• Liver transplant remains a limited resource and therefore there is unmet need for alternative therapies Persistent or incident hyperammonemia is more frequent in ACLF and is a risk factor for developing new onset organ failure and mortality. Therapeutic plasma exchange can lowers ammonia level in patients of ACLF and can improve survival over standard medical management. • Plasma exchange, by eliminating accumulated toxins (e.g., DAMPs) in ACLF can facilitate recovery of the failing liver and improvement in SIRS. • Replacement of the coagulation factors and other proteins and hence replacing the metabolic functions of the failing liver. • PE also leads to immunomodulation like shift toward TH2 balance, suppression of IL2 and IFN – Y production, reduction of inflammatory cytokines – TNF alpha and IL – 8 and helps in improvement of SIRS. |