| CTRI Number |
CTRI/2026/02/102728 [Registered on: 02/02/2026] Trial Registered Prospectively |
| Last Modified On: |
31/01/2026 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Comparison of carvedilol with propranolol for upper gastrointestinal bleeding in cirrhosus |
|
Scientific Title of Study
|
Carvedilol plus endoscopic variceal ligation versus propranolol plus endoscopic ligation for secondary prophylaxis of variceal bleed in cirrhosis: an open label randomized controlled trial |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Arka De |
| Designation |
Associate Professor |
| Affiliation |
Postgraduate Institute of Medical Education and Research |
| Address |
Room 033, Department of Hepatology, NHEB Ground floor,PGIMER
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9999816539 |
| Fax |
|
| Email |
arkascore@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Vishavdeep Singh Rana |
| Designation |
Senior Resident |
| Affiliation |
Postgraduate Institute of Medical Education and Research |
| Address |
Room 36A, Liver Office, NHEB, PGIMER
Department of Hepatology NHE Ground floor,PGIMER
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9876490007 |
| Fax |
|
| Email |
vishavdeeprana@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Vishavdeep Singh Rana |
| Designation |
Senior Resident |
| Affiliation |
Postgraduate Institute of Medical Education and Research |
| Address |
Room 36A, Liver Office, NHEB, PGIMER
Department of Hepatology NHE Ground floor,PGIMER
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9876490007 |
| Fax |
|
| Email |
vishavdeeprana@gmail.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Postgraduate Institute of Medical Education and Research |
| Address |
PGIMER, Sector 12, Chandigarh 160012 |
| Type of Sponsor |
Government medical college |
|
|
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 Vishavdeep Singh Rana |
Postgraduate Institute of Medical Education and Research |
Room No 033, Dept of Hepatology, NHEB, PGIMER, Sector 12, Chandigarh
Chandigarh
CHANDIGARH |
09876490007
vishavdeeprana@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee (Intramural) |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K721||Chronic hepatic failure, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Carvedilol |
Carvedilol will be started at 3.125 - 6.25 mg per day and up- titrated to a maximum of 12.5 mg per day. |
| Comparator Agent |
Propranolol |
Propranolol will be started at a dose of 20 - 40 mg per day and will be up-titrated to a maximum of 320 mg. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
1. Cirrhosis (of any etiology) as diagnosed on the basis of blood parameters, imaging or Fibro Scan
2. Source of UGIB is determined to be from esophageal varices and is successfully tackled using EVL. Variceal origin of UGIB will be considered based on endoscopic findings of:
a. Ongoing bleed from esophageal varices
b. Endoscopic stigmata of recent or high risk of bleed including red coloured streaks, blue hemocystic spot, cherry red sign and nipple sign
c. No other source of bleed and presence of bandable varices
3. Patients with acute kidney injury (International Ascites Club criteria) or acute- on-chronic liver failure (as per the CANONIC definition) at presentation will be included in the study only if these have resolved by the time of randomization
|
|
| ExclusionCriteria |
| Details |
1. Patients who are already receiving NSBB at index presentation
2. Failure to control UGIB using EVL
3. Presence of gastric varices
4. Presence of hepatocellular carcinoma or other active malignancy
5. Presence of portal vein thrombosis
6. Patients with acute-on-chronic liver failure (as per the CANONIC definition) at the time of randomization
7. Patients with acute kidney injury (by International Ascites Club criteria) at the time of randomization
8. Patients with bradycardia, sick-sinus syndrome, heart-block or other significant ECG abnormalities
9. Systolic blood pressure less than 90 mm-Hg or mean arterial pressure less than 70 mm-Hg at the time of randomization
10. Patients with bronchial asthma, chronic obstructive airway disease, peripheral vascular disease, Raynauds phenomenon or other contraindications to the use of non selective beta blockers.
11. Patients with transjugular intrahepatic portosystemic shunt (TIPS)
12. Patients having Refractory Ascites
13. Pregnant patients
14. Refusal to give informed consent
|
|
|
Method of Generating Random Sequence
|
Permuted block randomization, fixed |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Time to first variceal re-bleed |
within 12 months |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| - Early variceal re-bleed within 6-weeks of index EVL (bleed from post-EVL ulceration will not be considered as variceal re-bleed) |
within 12 months |
| 12-month transplant free survival |
within 12 months |
| Change in mean arterial pressure (MAP) |
at 1month, 6 months and 12 months |
Change in severity of portal hypertensive gastropathy (PHG). PHG will be graded as mild or severe depending on the absence or presence of central red spot.
|
at 12 months or last endoscopy |
| New onset acute kidney injury (AKI) |
within 12-months |
| New onset Hepatic Encephalopathy |
within 12 months |
| New onset Spontaneous Bacterial Peritonitis, other infections |
within 12 months |
| Ascites control |
at 6 and 12-months |
| Adverse events |
within 12 months |
|
|
Target Sample Size
|
Total Sample Size="96"
Sample Size from India="96"
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/ Phase 3 |
|
Date of First Enrollment (India)
|
13/02/2026 |
| 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="6"
Days="10" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| 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
|
Non-selective beta blockers (NSBB) are the mainstay of
pharmacological prophylaxis of variceal bleed in cirrhosis. While endoscopic
variceal ligation (EVL) or NSBB alone is recommended for decreasing the risk of
first variceal bleed (primary prophylaxis),
prevention of variceal re-bleed (secondary prophylaxis) requires the
combination of EVL and NSBB therapy.
Nadolol, propranolol and Carvedilol are the commonly
used NSBB for variceal bleed prophylaxis. Unlike Nadolol and propranolol,
Carvedilol has additional alpha-1 antagonistic action with consequent higher
reductions in intrahepatic vascular resistance and hepatic venous pressure
gradient (HVPG). The role of Carvedilol in primary prophylaxis of variceal
hemorrhage is well established. Overall, Carvedilol appears to be superior to
propranolol in reducing HVPG and is at par with EVL or propranolol in
preventing first episode of variceal bleeding.
However, the role of Carvedilol in secondary prophylaxis
of variceal hemorrhage remains a grey zone. Carvedilol causes a significantly
higher reduction in MAP in comparison to propranolol which can be particularly
problematic in patients with ascites who already have compromised systemic
hemodynamics. There have also been concerns regarding hyponatremia, increased
diuretic requirement and orthostatic hypotension with use of carvedilol. The
paucity of available data of carvedilol use for secondary prophylaxis and
concerns over its systemic effects is reflected in the fact that none of the
expert societies recommend carvedilol as a superior agent to propranolol for
secondary prophylaxis. In a recent retrospective non randomized study from Europe Carvedilol appeared to be superior to propranolol in decreasing HVPG, re-bleed
and liver related deaths without significant worsening of renal dysfunction. There
is no published RCT or prospective study on clinical outcomes with the use of
Carvedilol and EVL vis-a-vis propranolol and EVL for preventing variceal
re-bleed (secondary prophylaxis), in
patients with cirrhosis. This study is thus being planned to study the role of
Carvedilol in conjunction with EVL versus propranolol with EVL as secondary
prophylaxis in patients presenting with index variceal bleed. |