| CTRI Number |
CTRI/2025/01/079115 [Registered on: 21/01/2025] Trial Registered Prospectively |
| Last Modified On: |
21/01/2025 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Diagnostic
Preventive |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A study to assess the Endoscopic Treatment and Carvedilol Versus Carvedilol alone for Primary Prophylaxis of Patients With Hepatocellular Carcinoma and Esophageal Varice |
|
Scientific Title of Study
|
Combination of Endoscopic Treatment and Carvedilol Versus Carvedilol alone for Primary Prophylaxis of Patients With Hepatocellular Carcinoma and Esophageal Varices- An open-label parallel group randomized control trial |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Shalimar |
| Designation |
Professor |
| Affiliation |
All India Institute of Medical Sciences |
| Address |
Department of gastroenterology
AIIMS, Ansari Nagar
South
DELHI
110029
India |
| Phone |
9868397211 |
| Fax |
|
| Email |
drshalimar@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Shubam Jain |
| Designation |
Senior Resident |
| Affiliation |
All India Institute of Medical Sciences |
| Address |
Department of gastroenterology
AIIMS, Ansari Nagar
DELHI
110029
India |
| Phone |
9536045327 |
| Fax |
|
| Email |
sjthedarknight@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Shalimar |
| Designation |
Professor |
| Affiliation |
All India Institute of Medical Sciences |
| Address |
Department of gastroenterology
AIIMS, Ansari Nagar
DELHI
110029
India |
| Phone |
9868397211 |
| Fax |
|
| Email |
drshalimar@gmail.com |
|
|
Source of Monetary or Material Support
|
| All India Institute of medical sciences |
|
|
Primary Sponsor
|
| Name |
All India Institute of Medical Sciences |
| Address |
department of gastroenterology |
| 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 ANsari Nagar
South
DELHI |
09868397211
drshalimar@yahoo.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institute Ethics committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K746||Other and unspecified cirrhosis ofliver, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
carvedilol at 3.125 mg twice daily |
All patients in this arm will be started on carvedilol at 3.125 mg twice daily. The dose will be titrated every 7 days in the outpatient clinic to achieve a 25% drop in the resting pulse rate (PR) to no less than 55 beats/min and maintain the systolic blood pressure (SBP) 90 mm Hg. The maximal daily dose of carvedilol will be 12.5 mg twice daily. Treatment compliance will be assessed at each follow-up visit by questioning patients or their relatives and counting the number of pills whenever possible. |
| Intervention |
carvedilol at 3.125 mg twice daily and endoscopic band ligation |
All patients in this arm will be started on carvedilol at 3.125 mg twice daily. The dose will be titrated every 7 days in the outpatient clinic to achieve a 25% drop in the resting pulse rate (PR) to no less than 55 beats/min and maintain the systolic blood pressure (SBP) 90 mm Hg. The maximal daily dose of carvedilol will be 12.5 mg. In addition, EBL will be performed for patients in this group using a GIF-H190 or GIF-HQ190 endoscope (Olympus Optical, Tokyo, Japan) with an Omniview multiple band ligator (Medelec Systems Private Limited, New Delhi, India). EBL will be repeated every 3 weeks until variceal eradication is achieved on endoscopy. Follow-up endoscopy will be performed every 3 months after variceal eradication two times, followed by every 6 months for two times and annually thereafter. If follow-up endoscopy noted recurrent EVs, EBL will be restarted and done every 3 weeks until the recurrent EVs are endoscopically eradicated again. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
2. Cirrhotic patients with HCC (diagnosed based on the American Association for the Study of Liver Diseases criteria), including all BCLC classes
3. High-risk esophageal varices
|
|
| ExclusionCriteria |
| Details |
of esophageal variceal bleeding
2. Patients planned to receive Atezolizumab plus Bevacizumab (immune checkpoint inhibitor plus anti-VEGF antibody based therapy) for the management of HCC
3. Patients classified as BCLC-D (based on the tumor burden, performance status of the patient and liver functions)
4. Patients with acute-on-chronic liver failure (based on EASL-CLIF consortium definition or APASL definition)(16,17)
5. Previous treatment for esophageal varices, including EBL, endoscopic injection sclerotherapy (EIS) or TIPSS
6. History of use of NSBBs 2 weeks before the enrolment
7. Contraindications to carvedilol (atrioventricular block, heart failure, chronic obstructive pulmonary disease, asthma or severe peripheral arterial disease)
8. Pregnancy
9. Not willing to give consent
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| 1. To assess the cumulative incidence of first esophageal variceal bleeding among patients with HCC receiving carvedilol and EBL for primary prophylaxis as compared to carvedilol alone. |
1 year |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1. To assess the cumulative incidence of upper gastrointestinal (UGI) bleeding
2. To compare the incidence of non-bleeding liver-related decompensations
3. To compare the overall survival between the two groups
4. To compare the rate of adverse events between the 2 groups
5. To compare the quality of life between the two groups
|
1. 1 year
2. 1 year
3. 1 year
4. 1 year
5. 1 year |
|
|
Target Sample Size
|
Total Sample Size="220"
Sample Size from India="220"
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
|
N/A |
|
Date of First Enrollment (India)
|
03/02/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
03/02/2025 |
| 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)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Gastro-oesophageal variceal bleeding, a major complication of
portal hypertension (PHTN), is associated with high mortality rates.(1) Liver cirrhosis is
the most common cause of PHTN. Hepatocellular carcinoma (HCC) is a
life-threatening complication in patients with liver cirrhosis and is
associated with increased portal pressures.(2,3) More than 50% of patients with HCC have
esophageal varices (EVs) and, nearly half of these patients experience
esophageal variceal bleeding (EVB) if primary prevention strategies are not
implemented.(4,5) The prognosis of
patients with HCC and EVB is extremely poor, with rebleeding rates of 50% and
6-week mortality rate ranging from 26% to 48%, exceeding the rates seen in
patients without HCC.(6–8)
Non-selective beta-blockers
(NSBBs) and endoscopic band ligation (EBL) prevent variceal bleeding in
cirrhosis patients.(9) However, the risk factors
for EVB in patients with HCC are different from those in patients with
cirrhosis.(10) HCC increases the hepatic
venous pressure gradient (HVPG) through arteriovenous shunting within the tumor
and changes in hepatic architecture.(2) Tumour thrombosis in the
portal vein also contributes to PHTN and increases variceal bleeding.(3,11) Whether NSBBs alone are
sufficient to reduce HVPG levels and prevent EVB in patients with HCC is
unclear. Hence, this study aims to compare the efficacy and safety of the
combination EBL and NSBBs in the primary prevention of EVB in patients with HCC
with high-risk esophageal varices.(9) |