CTRI/2025/03/082426 [Registered on: 17/03/2025] Trial Registered Prospectively
Last Modified On:
11/03/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Medical Device
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A Study Comparing Two Treatments: Direct Glue Injection vs. Targeted Ultrasound-Guided Treatment with Glue and Coils to Stop Bleeding from Swollen Stomach Vein
Scientific Title of Study
An Open label Randomized controlled trial to assess the efficacy of EUS guided Coiling and Glue injection compared to conventional glue injection (Direct endoscopic injection) in prevention of late rebleed among patients with bleeding gastric varices
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NIL
NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Sudipta Dhar Chowdhury
Designation
Professor
Affiliation
Christian Medical College, Vellore
Address
Department of Gastroenterology
Christian Medical College,Vellore
Ranipet Campus
Ranipet,
Tamil Nadu 632517
Vellore TAMIL NADU 632517 India
Phone
9952311988
Fax
Email
sudiptadharchowdhury@gmail.com
Details of Contact Person Scientific Query
Name
Sudipta Dhar Chowdhury
Designation
Professor
Affiliation
Christian Medical College, Vellore
Address
Department of Gastroenterology
Christian Medical College,Vellore
Ranipet Campus
Ranipet,
Tamil Nadu 632517
Vellore TAMIL NADU 632517 India
Phone
9952311988
Fax
Email
sudiptadharchowdhury@gmail.com
Details of Contact Person Public Query
Name
Sudipta Dhar Chowdhury
Designation
Professor
Affiliation
Christian Medical College, Vellore
Address
Department of Gastroenterology
Christian Medical College,Vellore
Ranipet Campus
Ranipet,
Tamil Nadu 632517
Other [Not for profit - Non governmental organisation]
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 11
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Pramod Garg
All India Institute of Medical Sciences
Sri Aurobindo Marg,
Ansari Nagar, Ansari
Nagar East, New Delhi,
Delhi 110029
New Delhi
DELHI New Delhi DELHI
9810038116
pgarg10@gmail.com
Dr Sundeep Lakhtakia
Asian Institute of Gastroenterology
Survey No 136, 4/5,
Plot No 2/3, Mindspace
Rd, P Janardhan Reddy
Nagar, Gachibowli,
Hyderabad, Telangana
500032
Hyderabad
TELANGANA Hyderabad TELANGANA
9848040629
drsundeeplakhtakia@gmail.com
Dr Sudipta Dhar Chowdhury
Christian Medical College Vellore
Department of Gastroenterology,
Christian Medical College, Vellore
Ranipet - 632 517, Tamil Nadu, India. Vellore TAMIL NADU
9952311988
sudiptadharchowdhury@gmail.com
Dr Amol Bapaye
Deenanath Mangeshkar Hospital and Research Center
Department of Gastroenterology,
Deenanath Mangeshkar Hospital Road, near Mhatre Bridge, Vakil Nagar, Erandwane, Pune, Maharashtra 411004 Pune MAHARASHTRA
9822053654
amolbapaye@gmail.com
Dr Siddharth Srivastava
G B Pant Institute of Postgraduate Medical Education & Research
Department of Gastroenterology
G B Pant Institute of Postgraduate Medical Education & Research (GIPMER)
New Delhi- 110002 Central DELHI
Department of Gastroenterology
New PMSSY Rd, Raibareli Rd, Lucknow, Uttar Pradesh 226014 Lucknow UTTAR PRADESH
9235630450
praveer_rai@yahoo.com
Dr Pankaj Desai
Surat Institute of Digestive Sciences
Department of Gastroenterology
SIDS Hospital & Research Centre, off Ring Road, near Shell Petrol Pump, Sosyo Circle, Lane, Surat, Gujarat 395002 Surat GUJARAT
9824100681
drp_desai@hotmail.com
Dr Sridhar Sundaram
Tata Memorial Hospital
Department of Gastroenterology, Homi Babha Building, Dr. Ernest Borges Road, Parel East, Parel, Mumbai - 400012. Mumbai MAHARASHTRA
9860096846
drsridharsundaram@gmail.com
Details of Ethics Committee
No of Ethics Committees= 3
Name of Committee
Approval Status
Christian Medical College Vellore
Approved
Institutional Ethics Committee, Maulana Azad Medical College
Approved
SL Raheja Hospital, Mahim, Mumbai
Approved
Regulatory Clearance Status from DCGI
Status
Not Applicable
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: K318||Other specified diseases of stomach and duodenum,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Endoscopic glue injection
Endoscopic injection of cyanoacrylate glue
Comparator Agent
EUS guided coil and glue injection
Endoscopic ultrasound-guided coil embolization combined with cyanoacrylate glue injection
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
1. Upper GI bleed secondary to bleeding gastric varices
2. Gastric varices amenable to EUS/Endoscopic therapy
ExclusionCriteria
Details
1. Pregnancy
2. Platelets count less than 50,000 
3. International Normalized Rate (INR) more than  2.
4. Patients with Child C cirrhosis
5. Patients in altered sensorium
6. Hepatorenal syndrome
7. Sepsis
8. Multiorgan failure,
9. Previous endoscopic treatment for GVs,
10. Malignancy
11. Portal and splenic vein thrombosis
12. Oesophageal stricture
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare the efficacy of DEI of CYA versus EUS guided coiling and glue for control of late rebleeding in patients with bleeding gastric varices
Follow up at 2 weeks, 4 weeks and 12 weeks after therapy
Secondary Outcome
Outcome
TimePoints
Early rebleeding
Complications,
Duration of hospital stay
Cost of therapy
Early rebleeding - 2 - 5 days of therapy
Target Sample Size
Total Sample Size="110" Sample Size from India="110" 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/ Phase 4
Date of First Enrollment (India)
01/05/2025
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)
Not Yet Recruiting
Recruitment Status of Trial (India)
Open to Recruitment
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
Introduction:
Gastric varices (GV) develop as a consequence of portal hypertension. GV bleeding is associated with a higher risk of rebleeding, morbidity and mortality than oesophageal varices. [1] Initial management for gastric variceal bleeding includes assessment and management of circulatory status, respiratory status and administration of vasoactive drugs and antibiotics. In the 1980s Soehendra et al described a technique for endoscopic guided direct injection of gastric varices with bucrylate.[2] Since then direct endoscopic injection (DEI) of cyanoacrylate (CYA) into the gastric varix has been the main stay of therapy.[3] DEI is an effective therapy for managing gastric variceal bleeding. However a number of complications including cast extrusion, sepsis, embolism of glue thrombus, ulceration etc have been reported with DEI of cyanoacrylate. Endoscopic ultrasound (EUS) guided injection of coils and CYA into varices is a recently described modality of treatment of gastric varices. [4] EUS guided therapy has certain advantages of over DEI. With the help of EUS a precise localisation and injection of varices is possible. The use of coil can reduce the volume of CYA required for obliteration of varices. EUS can also confirm the complete obliteration of a target varix.[5] In a recent multicenter propensity score matched retrospective study, EUS guided coiling and glue injection was found to have a better efficacy compared to DEI in prevention of rebleed. [8] In a recent network meta analysis, compared to DEI the risk of rebleed was lower with EUS guided coil and glue injection. [6] In a randomized controlled trial the risk of rebleed was lower with EUS Glue and coil versus coiling alone. [7] However, there is no randomised study that contrasts the likelihood of a late rebleed after direct endoscopic injection against EUS guide glue and coil. The present study is being done with an aim to compare DEI of CYA to EUS guided coil and CYA in bleeding GV in prevention of late rebleeding in patients with bleeding GV.
Objective: 1. Primary objective: To compare the efficacy of DEI of CYA versus EUS guided coiling and glue for control of late rebleeding in patients with bleeding gastric varices Rebleeding defined by any of the following criteria:Death, Fresh hematemesis or >100 mL of fresh red NG aspirate, Development of hypovolemic shock, more than 2 g/dL drop in Hb within any 24 hour period (without transfusion) 2. Secondary objectives: early rebleeding (within 2 - 5 days of therapy), complication, duration of hospital stay, cost of therapy Methods: All consecutive patients admitted during the study period with gastric variceal bleed secondary to cirrhosis related portal hypertension at the participating centres will be screened for eligibility and those fulfilling the inclusion criteria will be included in the study Inclusion criteria: Age > 18 years, a.Upper GI bleed secondary to bleeding gastric varices, Gastric varices amenable to EUS/Endoscopic therapy (Hashizome’s – F2 and F3) Exclusion criteria: Pregnancy, Platelets count less than 50,000 /mL and International Normalized Rate (INR) > 2, Patients with Child C cirrhosis, Patients in altered sensorium, Hepatorenal syndrome , Sepsis, Multiorgan failure, Previous endoscopic treatment for GVs, Malignancy, Portal and splenic vein thrombosis, Oesophageal stricture Setting: tertiary care centre Study design: The study is designed as a prospective open label randomized controlled trial to assess the efficacy of EUS guided glue and coil injection versus direct endoscopic injection of cyanoacrylate glue in patients with bleeding gastric varices for control of late rebleeding. Consecutive patients will be randomly assigned to either treatment group. Study duration: 2 years Randomisation: Randomization will be done centrally. A computer generated randomization sequence with variable block size will be generated by the Department of Biostatistics at CMC Vellore. The randomization list will be generated for 110 patients (55 in each arm). Allocation concealment: Sequentially numbered opaque sealed envelopes containing allocation information will be created by a statistician who is not involved in the study. The study envelopes will be stored centrally in a secure locker and will be opened once a patient is recruited in the study and the participating site obtains consent from the patient. Details of the patient will be noted on the envelop cover Trial procedure: EUS Glue and Coil: Prior to EUS examination a through endoscopic examination will be done to ascertain the varix location and presence of RCS. Following the endoscopic examination IV ANTIBIOTIC will be administered and a linear EUS scope will be positioned in the distal oesophagus/gastric fundus to assess the varices. Water may be instilled in the gastric fundus to improve the acoustic coupling. The variceal diameter at EUS will be noted (Diameter- The maximum short-axis diameter of GV (mm)). Presence of perforating veins and perigastric veins will also be located and noted. For EUS guided coiling; a coil of ~1.2 times the short axis diameter of the gastric varix will be chosen. A 19 G EUS FNAC needle will be used to inject the coil into the varix. This will be followed by injection of cyanoacrylate 0.5 ml – 1 ml through the EUS FNAC needle. Repeat injection may be required if there is incomplete obliteration of the GV on colour doppler. The procedure will be considered complete once there is no flow within the varix Direct endoscopic glue injection:A through endoscopic examination will be done to ascertain the varix location and presence of RCS. Following the endoscopic examination IV ANTIBIOTIC will be administered. A sclerotherapy needle primed with saline will be used to puncture the GV. 2 ml of distilled water will be then injected to confirm correct needle placement. Following this 1 ml of Cyanoacrylate glue would be injected under endoscopic visualization followed by injection of 2ml of distilled water. The procedure will be considered complete if there is a change in colour of GV or the GV appears firm on gentle probing.
Evaluation and Monitoring of participants: The procedure details will be recorded (number of coils/amount of CYA) any adverse event related to the procedure will be recorded. The participants will be followed up at 2 weeks/ 4 weeks and 12 weeks after discharge from hospital. A structured questionnaire will be administered to the patients to ascertain likelihood of rebleed during follow up. Routine blood examinations as per standard of care will be done at each follow up visit.
Sample size: In a retrospective propensity score matched study the incidence of rebleed in DEI was 40 % and the proportion of rebleeding in the EUS guided glue and coil injection was 13.8%. [8] The sample size was estimated under the assumption that the proportion of patients who present with late rebleeding would be 40% in the DEI group and 15% in the EUS guided coil and glue injection group. With an alpha of 0.05 and a power of 0.80 a 2 tailed test and a 10 % drop the number of patients to be included in each arm is 55. Pre-planned interim analysis: We will do an interim analysis after including half of the sample size is achieved to see any trend towards intervention or futility. References: 1. Wani ZA, Bhat RA, Bhadoria AS, Maiwall R, Choudhury A. Gastric varices: Classification, endoscopic and ultrasonographic management. J Res Med Sci Off J Isfahan Univ Med Sci. 2015;20:1200–7. 2. Soehendra N, Nam VC, Grimm H, Kempeneers I. Endoscopic obliteration of large esophagogastric varices with bucrylate. Endoscopy. 1986;18:25–6. 3. de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C, Baveno VII Faculty. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022;76:959–74. 4. Binmoeller KF, Weilert F, Shah JN, Kim J. EUS-guided transesophageal treatment of gastric fundal varices with combined coiling and cyanoacrylate glue injection (with videos). Gastrointest Endosc. 2011;74:1019–25. 5. Bhatia V. Endoscopic Ultrasound (EUS) for Esophageal and Gastric Varices: How Can it Improve the Outcomes and Reduce Complications of Glue Injection. J Clin Exp Hepatol. 2012;2:70–4. 6. Samanta J, Nabi Z, Facciorusso A, Dhar J, Akbar W, Das A, et al. EUS-guided coil and glue injection versus endoscopic glue injection for gastric varices: International multicentre propensity-matched analysis. Liver Int Off J Int Assoc Study Liver. 2023;43:1783–92. 9. Giri S, Jearth V, Seth V, Darak H, Sundaram S. Comparison of efficacy and safety of endoscopic and radiological interventions for gastric varices: A systematic review and network meta-analysis. Clin Exp Hepatol. 2023;9:57–70. 7. Robles-Medranda C, Oleas R, Valero M, Puga-Tejada M, Baquerizo-Burgos J, Ospina J, et al. Endoscopic ultrasonography-guided deployment of embolization coils and cyanoacrylate injection in gastric varices versus coiling alone: a randomized trial. Endoscopy. 2020;52:268–75.