Ignite Creation Date:
2025-12-24 @ 2:15 PM
Ignite Modification Date:
2025-12-29 @ 6:53 AM
Study NCT ID:
NCT07168395
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-09-11
First Post:
2025-09-01
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pre-emptive RTO for An Early Detected Gastric Varices in CT/MR Angiogram Trial
Sponsor:
University of California, Los Angeles
Organization:
Study Overview
Official Title:
Pre-emptive RTO for An Early Detected Gastric Varices in CT/MR Angiogram Trial (PRADA Trial)
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PRADA
Brief Summary:
A number of treatment modalities are currently in use for gastric variceal bleeding (GVB). Balloon-occluded, plug-assisted, and coil-assisted retrograde transvenous obliteration (RTO) procedures are described in the literature as treatments for GVB after a bleeding episode occurs. Preliminary data suggests that prophylactic treatment of gastric varices may improve patient outcomes compared to conservative management. This study aims to compare pre-emptive treatment of gastric varices with current recommended medical management in a randomized prospective study design. Eligible patients will be randomized to receive RTO or to continue conservative management. Patients will be followed for up to 2 years for comparison of clinical outcomes, including episodes of gastric variceal bleeding, overall survival and transplant-free survival, complications, and secondary interventions.
Detailed Description:
Gastroesophageal varices occur in approximately 50% of patients with liver cirrhosis. Specifically, gastric varices (GV) are responsible for roughly 10-30% of all variceal hemorrhage which is less than their counterpart esophageal varices. Despite their lower recurrence rates, gastric variceal bleeds (GVB) are associated with higher mortality, with an estimated 35-90% of patients developing rebleeding after achieving hemostasis.
Currently, there are several treatments for GVB that include endoscopic injection therapies, percutaneous antegrade transhepatic obliteration (ATO), transjugular portosystemic shunt placement (TIPS), splenic artery embolization (SAE), and surgical treatment. However, these procedures in previously studied trials have well-documented risks that compromise clinical outcomes. One specific interventional radiology procedure that has maintained a positive reputation in its use for gastric variceal bleeds is balloon-occluded retrograde transvenous obliteration (BRTO). This was first reported by Kanagawa et al. in the early 1990s; BRTO remains a well-accepted method of treatment of gastric fundal varices with gastrorenal or gastrophrenic shunts because of its minimally invasive nature and highly effective results, with studies showing up to 95% clinical success rate in stopping variceal bleeding. However, this procedure still has its own risks and limitations. For example, BRTO requires injection of a sclerosing agent (e.g. sodium tetradecyl sulfate or ethanolamine oleate), which has been associated with pulmonary venothrombotic embolization, portal vein thrombosis, anaphylactic reaction, hemolysis, renal tubular disturbance and acute renal failure. Furthermore, BRTO involves an indwelling occlusive balloon that remains inflated for hours, thus resulting in lengthy procedure times with increased necessary hospital resources and serious potential complication for balloon rupture. Despite these risks for BRTO complications, the procedure has been largely adopted by the IR community for its high success in controlling acute GVB, improving liver function, and well-documented improvement of hepatic encephalopathy.
In 2013, Gwon et al. modified BRTO with a vascular plug replacing the indwelling balloon to minimize the technical and clinical complications associated with BRTO with results suggesting plug-assisted RTO (PARTO) to be simple, safe, and an effective treatment for GV. A year later, Lee et al., presented their own preliminary findings with a modified BRTO procedure involving coils instead of balloons with the conclusion that coil-assisted retrograde transvenous obliteration (CARTO) treatment of portal hypertension variceal bleeding was a feasible and safer alternative than BRTO. A case report by Terada et al. highlighted the benefits to CARTO in a few ways: 1) if the shunt was not conducive to balloon placement then CARTO was a superior alternative 2) a steerable catheter reduced the required access routes and 3) steerable catheters allow for selective catheterization of acute-angle branching vessels. During the past decade, CARTO and PARTO have evolved as a simpler and possibly safer alternative to BRTO with comparable efficacy and favorable complication profiles. Yet, despite the promising preliminary results during these last decades on RTO for GVB, there is limited data in regard to its long-term efficacy. Furthermore, given the everchanging treatments for prophylactic treatment of GVB per AASLD guidelines, there is not enough data to support RTO as a preemptive intervention to protect against primary GVB. This study is aimed at exploring this latter question.
Per AASLD guidelines, primary prophylactic management for prevention of first GVB is a non-selective beta blocker. These same guidelines recommend against either TIPS or BRTO for primary prophylaxis of GVB. Yet the AASLD guidelines for treatment change considerably after patient endorses their first variceal bleeding. For instance, if the patient had a GOV1 hemorrhage, first-line treatment against gastric variceal rebleeding is both a non-selective beta blocker and an endoscopic variceal ligation. If the patient had a GOV2 or IGV1 hemorrhage, then first-line treatment against gastric variceal rebleeding can be either TIPS or BRTO. While these guidelines provide a framework for gastric variceal management, currently, non-selective beta-blockers serve as the only prophylactic treatment against primary GVB. The current study challenges this guideline to see whether CARTO or PARTO, a procedure with high efficacy and high safety profile, can be integrated as an alternative prophylactic treatment against primary GVB.
In the investigators' recent retrospective study (unpublished data), the investigators demonstrated that the cumulative survival rates in patients who received prophylactic CARTO/PARTO were 94% and 62% at 60 and 120 months. In contrast, those who received CARTO/PARTO for active bleeding were 43% and 0% at 60 and 120 months, respectively. There was a significant difference between the two groups (p=0.00035). This finding needs to be further investigated in prospective trials to validate these findings, which could potentially change how patients with GV are treated.
In this study, the investigators will perform a single-center, prospective, randomized controlled trial to evaluate the effectiveness in reducing primary GVB between preemptive RTO and the current conservative standard of care in patients with gastric varices. The results of this study will guide clinical practice and standard of care management of RTO as a possible alternative to prophylactic treatment against primary GVB. The study will also collect extensive follow-up care in all participants to continue cultivating data for RTO-associated complications and assessing its effect on necessary secondary interventions. As RTO procedures continue to evolve and become more widely used, this study will have the ability to contribute important information towards the indication and guidance of CARTO as an alternative prophylactic treatment.
Currently, there are several treatments for GVB that include endoscopic injection therapies, percutaneous antegrade transhepatic obliteration (ATO), transjugular portosystemic shunt placement (TIPS), splenic artery embolization (SAE), and surgical treatment. However, these procedures in previously studied trials have well-documented risks that compromise clinical outcomes. One specific interventional radiology procedure that has maintained a positive reputation in its use for gastric variceal bleeds is balloon-occluded retrograde transvenous obliteration (BRTO). This was first reported by Kanagawa et al. in the early 1990s; BRTO remains a well-accepted method of treatment of gastric fundal varices with gastrorenal or gastrophrenic shunts because of its minimally invasive nature and highly effective results, with studies showing up to 95% clinical success rate in stopping variceal bleeding. However, this procedure still has its own risks and limitations. For example, BRTO requires injection of a sclerosing agent (e.g. sodium tetradecyl sulfate or ethanolamine oleate), which has been associated with pulmonary venothrombotic embolization, portal vein thrombosis, anaphylactic reaction, hemolysis, renal tubular disturbance and acute renal failure. Furthermore, BRTO involves an indwelling occlusive balloon that remains inflated for hours, thus resulting in lengthy procedure times with increased necessary hospital resources and serious potential complication for balloon rupture. Despite these risks for BRTO complications, the procedure has been largely adopted by the IR community for its high success in controlling acute GVB, improving liver function, and well-documented improvement of hepatic encephalopathy.
In 2013, Gwon et al. modified BRTO with a vascular plug replacing the indwelling balloon to minimize the technical and clinical complications associated with BRTO with results suggesting plug-assisted RTO (PARTO) to be simple, safe, and an effective treatment for GV. A year later, Lee et al., presented their own preliminary findings with a modified BRTO procedure involving coils instead of balloons with the conclusion that coil-assisted retrograde transvenous obliteration (CARTO) treatment of portal hypertension variceal bleeding was a feasible and safer alternative than BRTO. A case report by Terada et al. highlighted the benefits to CARTO in a few ways: 1) if the shunt was not conducive to balloon placement then CARTO was a superior alternative 2) a steerable catheter reduced the required access routes and 3) steerable catheters allow for selective catheterization of acute-angle branching vessels. During the past decade, CARTO and PARTO have evolved as a simpler and possibly safer alternative to BRTO with comparable efficacy and favorable complication profiles. Yet, despite the promising preliminary results during these last decades on RTO for GVB, there is limited data in regard to its long-term efficacy. Furthermore, given the everchanging treatments for prophylactic treatment of GVB per AASLD guidelines, there is not enough data to support RTO as a preemptive intervention to protect against primary GVB. This study is aimed at exploring this latter question.
Per AASLD guidelines, primary prophylactic management for prevention of first GVB is a non-selective beta blocker. These same guidelines recommend against either TIPS or BRTO for primary prophylaxis of GVB. Yet the AASLD guidelines for treatment change considerably after patient endorses their first variceal bleeding. For instance, if the patient had a GOV1 hemorrhage, first-line treatment against gastric variceal rebleeding is both a non-selective beta blocker and an endoscopic variceal ligation. If the patient had a GOV2 or IGV1 hemorrhage, then first-line treatment against gastric variceal rebleeding can be either TIPS or BRTO. While these guidelines provide a framework for gastric variceal management, currently, non-selective beta-blockers serve as the only prophylactic treatment against primary GVB. The current study challenges this guideline to see whether CARTO or PARTO, a procedure with high efficacy and high safety profile, can be integrated as an alternative prophylactic treatment against primary GVB.
In the investigators' recent retrospective study (unpublished data), the investigators demonstrated that the cumulative survival rates in patients who received prophylactic CARTO/PARTO were 94% and 62% at 60 and 120 months. In contrast, those who received CARTO/PARTO for active bleeding were 43% and 0% at 60 and 120 months, respectively. There was a significant difference between the two groups (p=0.00035). This finding needs to be further investigated in prospective trials to validate these findings, which could potentially change how patients with GV are treated.
In this study, the investigators will perform a single-center, prospective, randomized controlled trial to evaluate the effectiveness in reducing primary GVB between preemptive RTO and the current conservative standard of care in patients with gastric varices. The results of this study will guide clinical practice and standard of care management of RTO as a possible alternative to prophylactic treatment against primary GVB. The study will also collect extensive follow-up care in all participants to continue cultivating data for RTO-associated complications and assessing its effect on necessary secondary interventions. As RTO procedures continue to evolve and become more widely used, this study will have the ability to contribute important information towards the indication and guidance of CARTO as an alternative prophylactic treatment.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: