Clinical trial NCT06772480: Thalidomide Versus Argon Plasma Coagulation in Gastric Antral Vascular Ectasia(GAVE)-Related Anaemia in Cirrhosis (TAG Trial)
Official title: Thalidomide Versus Argon Plasma Coagulation in Gastric Antral Vascular Ectasia(GAVE)-Related Anaemia in Cirrhosis (TAG Trial)- A Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Liver Cirrhosis
Gastric Antral Vascular Ectasia
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2025-01-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Gastric Antral Vascular Ectasia (GAVE) is an erosive form of gastritis distinguished by veno-capillary ectasia, which manifests as tortuous columns of dilated vessels. Histologically, these vessels show dilated mucosal capillaries filled with fibrin thrombi, accompanied by fibromuscular hyperplasia and spindle cell proliferation of the lamina propria. GAVE is prevalent in about 12% of patients with cirrhosis, with 60-70% of these patients becoming transfusion-dependent due to severe anaemia caused by GAVE related bleeding. The most commonly used treatment for GAVE is endoscopic therapy using Argon Plasma Coagulation (APC), which, while effective, often requires multiple sessions due to a high recurrence rate of 30-60%. These frequent interventions increase the burden on patients and healthcare systems. As a result, alternative treatments have been sought. Thalidomide, known for its potent antiangiogenic properties, significantly lowers vascular endothelial growth factor (VEGF) levels, offering a promising non-invasive treatment option. Early studies, such as those by García-Pagán have demonstrated thalidomide's effectiveness in reducing transfusion requirements and managing bleeding in cirrhotic patients with GAVE, yet its comprehensive efficacy and safety profile remains under-studied. This project aims to rigorously evaluate the efficacy and safety of thalidomide compared to APC in managing GAVE-related anemia in cirrhotic patients. Through a controlled trial, this study will provide vital data to potentially shift treatment paradigms, enhance patient quality of life, and reduce the need for repetitive invasive procedures.

Detailed description: Aim: To evaluate and compare the efficacy and safety of thalidomide with argon plasma coagulation (APC) in managing gastric antral vascular ectasia (GAVE)-related anaemia in patients with cirrhosis.

Hypothesis: Thalidomide, due to its antiangiogenic effects, will more effectively reduce GAVE-related bleeding, improve haemoglobin levels, and decrease transfusion dependency compared to APC in patients with cirrhosis and GAVE-related anaemia.

Study Design:

Single-centre, open-label, randomised controlled trial to compare the efficacy and safety of thalidomide versus argon plasma coagulation (APC) in managing GAVE-related anaemia in cirrhotic patients.

Study Population:

Adult patients (aged 18-65 years) diagnosed with cirrhosis and endoscopically confirmed GAVE-related anaemia, presenting at the Institute of Liver and Biliary Sciences.

Randomization: Patients will be randomly assigned to receive either thalidomide or APC in a 1:1 ratio by block randomization method with block size of 10 and it will be implemented by using ILBS IWRS facility.

Follow-up and Assessments:

* Patients will be followed every two weeks for the first month, then monthly up to six months. Assessments will include haemoglobin levels, the number of transfused blood units, the frequency of bleeding episodes, hospitalizations, and the number of required endoscopic sessions.
* Adverse effects will be monitored and recorded at each visit.

Eligibility criteria: Inclusion Criteria:

1. Adult patients (aged ≥18 - 65years)
2. Cirrhosis
3. Endoscopically confirmed diagnosis of GAVE

   1. +/- GAVE with active ooze
   2. Iron deficiency anemia\*
4. Ability to provide informed consent

Exclusion Criteria:

1. CTP \>/=13
2. Active GI Bleeding is caused by a cause other than GAVE.
3. Renal insufficiency ( Creatinine \>3mg/dL and/or on RRT)
4. Pregnancy or childbearing age
5. Contraindications to thalidomide therapy: Severe peripheral neuropathy or seizures or a history of thromboembolic disease.
6. Use of antiangiogenic drugs
7. Bevacizumab, steroids, octreotide
8. Severe cardiopulmonary disorders
9. H/o thalidomide use in the past 3months
10. Contraindications to APC: Coagulopathy( Pacemaker or implantable defibrillator, Platelet \<45000, INR: \>1.8 )
11. Overt Hepatic Encephalopathy

Primary outcomes:
measure: Mean increase in hemoglobin levels from baseline
timeFrame: 4 months
Secondary outcomes:
measure: Atleast 50 percent change in requirement of PRBCs transfusions at the end of 4 months
timeFrame: 4 months
measure: Increase in serum iron levels, percent transferrin saturation at the end of 4months
timeFrame: 4 months
measure: Change in amount of PRBC's transfused at the end of 4 months.
timeFrame: 4 months
measure: Change in GAVE related bleeding episodes at the end of 4 months
timeFrame: 4 months
measure: Number of hospitalizations due to GAVE related anemia, in 4 months
timeFrame: 4 months
measure: Duration of days of hospitalization due to GAVE related anemia in 4 months
timeFrame: 4 months
measure: Need of rescue endoscopic sessions in 4 months in thalidomide group
timeFrame: 4 months
measure: Endoscopic resolution of GAVE at the end of 4 months
timeFrame: 4 months
measure: Change in VEGF levels in Thalidomide group at the end of 4 months
timeFrame: 4 months
measure: Change in pepsinogen levels in Thalidomide group at the end of 4 months
timeFrame: 4 months
measure: Change in gastrin levels in Thalidomide group at the end of 4 months
timeFrame: 4 months
measure: Adverse events in each group at the end of 4 months
timeFrame: 4 months
measure: Quality of life measures - Short Form 36
timeFrame: 4 months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver & Biliary Sciences (ILBS)
state: Delhi
Study officials:
References: