Ignite Creation Date:
2025-12-25 @ 1:34 AM
Ignite Modification Date:
2025-12-25 @ 11:48 PM
Study NCT ID:
NCT04252794
Status:
COMPLETED
Last Update Posted:
2024-04-10
First Post:
2020-01-10
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Graft Inflow Modulation for Portal Hyper-perfusion in Live Donor Liver Transplantation
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008103', 'term': 'Liver Cirrhosis'}], 'ancestors': [{'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005355', 'term': 'Fibrosis'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 75}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-08-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-04', 'completionDateStruct': {'date': '2023-07-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-04-08', 'studyFirstSubmitDate': '2020-01-10', 'studyFirstSubmitQcDate': '2020-01-31', 'lastUpdatePostDateStruct': {'date': '2024-04-10', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-02-05', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-07-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of early graft dysfunction', 'timeFrame': 'first postoperative month', 'description': 'Number of patients who develop early graft dysfunction in each group'}], 'secondaryOutcomes': [{'measure': 'Time to normalisation of bilirubin', 'timeFrame': 'first postoperative month', 'description': 'time to normalisation of bilirubin (in days)'}, {'measure': 'Time to normalisation of INR', 'timeFrame': 'first postoperative month', 'description': 'time to normalisation of INR (in days)'}, {'measure': 'Time to normalisation of ascites output', 'timeFrame': 'first postoperative month', 'description': 'time to normalisation of ascites output (in days)'}, {'measure': 'Morbidity', 'timeFrame': 'first postoperative month', 'description': 'Morbidity as per Clavein Dindo classfification'}, {'measure': 'ICU stay', 'timeFrame': 'first operative month', 'description': 'Duration of ICU stay (in days)'}, {'measure': 'Mortality', 'timeFrame': 'first postoperative month', 'description': 'death'}, {'measure': 'Total hospital stay', 'timeFrame': 'till 3 months after surgery', 'description': 'duration of total stay in hospital after liver transplatation (in days)'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Cirrhosis, Liver']}, 'referencesModule': {'references': [{'pmid': '10075602', 'type': 'RESULT', 'citation': 'Kiuchi T, Kasahara M, Uryuhara K, Inomata Y, Uemoto S, Asonuma K, Egawa H, Fujita S, Hayashi M, Tanaka K. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. Transplantation. 1999 Jan 27;67(2):321-7. doi: 10.1097/00007890-199901270-00024.'}, {'pmid': '29752783', 'type': 'RESULT', 'citation': 'Bell R, Pandanaboyana S, Upasani V, Prasad R. Impact of graft-to-recipient weight ratio on small-for-size syndrome following living donor liver transplantation. ANZ J Surg. 2018 May;88(5):415-420. doi: 10.1111/ans.14245.'}, {'pmid': '24370677', 'type': 'RESULT', 'citation': 'Vasavada BB, Chen CL, Zakaria M. Portal flow is the main predictor of early graft dysfunction regardless of the GRWR status in living donor liver transplantation - a retrospective analysis of 134 patients. Int J Surg. 2014;12(2):177-80. doi: 10.1016/j.ijsu.2013.12.006. Epub 2013 Dec 25.'}, {'pmid': '25299370', 'type': 'RESULT', 'citation': "Vasavada B, Chen CL, Zakaria M. Using low graft/recipient's body weight ratio graft with portal flow modulation an effective way to prevent small-for-size syndrome in living-donor liver transplant: a retrospective analysis. Exp Clin Transplant. 2014 Oct;12(5):437-42."}, {'pmid': '22260833', 'type': 'RESULT', 'citation': 'Lei JY, Yan LN, Li B, Wen TF, Wang WT, Xu MQ, Yang JY. Graft size alone should not affect donors selection and be used to predict the prognosis of recipients after living donor liver transplantation. Hepatogastroenterology. 2012 Jan-Feb;59(113):224-7. doi: 10.5754/hge11035.'}, {'pmid': '16861970', 'type': 'RESULT', 'citation': 'Demetris AJ, Kelly DM, Eghtesad B, Fontes P, Wallis Marsh J, Tom K, Tan HP, Shaw-Stiffel T, Boig L, Novelli P, Planinsic R, Fung JJ, Marcos A. Pathophysiologic observations and histopathologic recognition of the portal hyperperfusion or small-for-size syndrome. Am J Surg Pathol. 2006 Aug;30(8):986-93. doi: 10.1097/00000478-200608000-00009.'}, {'pmid': '11267312', 'type': 'RESULT', 'citation': 'Shimamura T, Taniguchi M, Jin MB, Suzuki T, Matsushita M, Furukawa H, Todo S. Excessive portal venous inflow as a cause of allograft dysfunction in small-for-size living donor liver transplantation. Transplant Proc. 2001 Feb-Mar;33(1-2):1331. doi: 10.1016/s0041-1345(00)02496-9. No abstract available.'}, {'pmid': '20430194', 'type': 'RESULT', 'citation': 'Ou HY, Huang TL, Chen TY, Tsang LL, Chen CL, Cheng YF. Early modulation of portal graft inflow in adult living donor liver transplant recipients with high portal inflow detected by intraoperative color Doppler ultrasound. Transplant Proc. 2010 Apr;42(3):876-8. doi: 10.1016/j.transproceed.2010.02.064.'}, {'pmid': '20517905', 'type': 'RESULT', 'citation': 'Ogura Y, Hori T, El Moghazy WM, Yoshizawa A, Oike F, Mori A, Kaido T, Takada Y, Uemoto S. Portal pressure <15 mm Hg is a key for successful adult living donor liver transplantation utilizing smaller grafts than before. Liver Transpl. 2010 Jun;16(6):718-28. doi: 10.1002/lt.22059.'}, {'pmid': '25080864', 'type': 'RESULT', 'citation': 'Wang H, Ikegami T, Harada N, Yoshizumi T, Soejima Y, Uchiyama H, Yamashita Y, Itoh S, Harimoto N, Kawanaka H, Shirabe K, Maehara Y. Optimal changes in portal hemodynamics induced by splenectomy during living donor liver transplantation. Surg Today. 2015 Aug;45(8):979-85. doi: 10.1007/s00595-014-0999-9. Epub 2014 Aug 2.'}, {'pmid': '16741929', 'type': 'RESULT', 'citation': 'Luca A, Miraglia R, Caruso S, Milazzo M, Gidelli B, Bosch J. Effects of splenic artery occlusion on portal pressure in patients with cirrhosis and portal hypertension. Liver Transpl. 2006 Aug;12(8):1237-43. doi: 10.1002/lt.20762.'}, {'pmid': '27084787', 'type': 'RESULT', 'citation': 'Osman AM, Hosny AA, El-Shazli MA, Uemoto S, Abdelaziz O, Helmy AS. A portal pressure cut-off of 15 versus a cut-off of 20 for prevention of small-for-size syndrome in liver transplantation: A comparative study. Hepatol Res. 2017 Mar;47(4):293-302. doi: 10.1111/hepr.12727. Epub 2016 May 11.'}, {'pmid': '12942477', 'type': 'RESULT', 'citation': 'Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients. Liver Transpl. 2003 Sep;9(9):S36-41. doi: 10.1053/jlts.2003.50200.'}, {'pmid': '18261170', 'type': 'RESULT', 'citation': 'Yamada T, Tanaka K, Uryuhara K, Ito K, Takada Y, Uemoto S. Selective hemi-portocaval shunt based on portal vein pressure for small-for-size graft in adult living donor liver transplantation. Am J Transplant. 2008 Apr;8(4):847-53. doi: 10.1111/j.1600-6143.2007.02144.x. Epub 2008 Feb 5.'}, {'pmid': '18791439', 'type': 'RESULT', 'citation': 'Umeda Y, Yagi T, Sadamori H, Matsukawa H, Matsuda H, Shinoura S, Mizuno K, Yoshida R, Iwamoto T, Satoh D, Tanaka N. Effects of prophylactic splenic artery modulation on portal overperfusion and liver regeneration in small-for-size graft. Transplantation. 2008 Sep 15;86(5):673-80. doi: 10.1097/TP.0b013e318181e02d.'}]}, 'descriptionModule': {'briefSummary': "In this study, the investigators aim to prove that performing graft inflow modulation (GIM) in liver with portal hyper-perfusion is beneficial for early graft function postoperatively. Grafts at risk for portal hyper-perfusion will be identified by doing an intraoperative Doppler after reperfusion. In group A, the investigators will take 21 liver transplant recipients after reperfusion, randomly allocated, who will undergo intraoperative graft inflow modulation by splenic artery ligation. In group B, the investigators will be analyzing another randomly allocated 21 patients, who will not undergo any graft inflow modulation. The investigators will be analyzing trend of LFT's (liver function tests) after surgery, time for normalization of bilirubin, INR (international normalised ratio) and decrease in ascites, morbidity, mortality, ICU (intensive care unit) and total hospital stay.", 'detailedDescription': "Due to shortage of deceased donor organs, LDLT (living donor living transplantation) is gaining importance all over world. Previous studies have showed poor outcomes with donor grafts having GRWR (graft to recipient weight ratio) \\< 0.8 due to development of SFSS (Small for Size Syndrome) where the graft is too small to meet the recipient's metabolic demands. SFSS is characterised by prolonged cholestasis, intractable ascites, prolonged INR and encephalopathy. However, it is not always possible to obtain larger graft from live donor owing to the risk's associated to donor. Various techniques have been developed in order to manage a smaller graft in recipient (ex: hemiportocaval shunts, splenic artery ligation, splenectomy). HPCS (hemiportocaval shunt) have been associated with risks of portal steal phenomenon and encephalopathy. Splenectomy is associated with increased risks of infections / sepsis and portal vein thrombosis postoperatively. Splenic artery ligation close to its origin is associated with least risks and is increasingly being used as the method of graft inflow modulation when required.\n\nRecent studies have showed that Portal Flow Hemodynamics are more important than GRWR in predicting the occurrence of SFSS. Grafts whose GRWR is \\> 0.8 can also show features of SFSS after ruling out all other causes (5). Persistent portal hypertension leads to sinusoidal endothelial injury, haemorrhage, oedema and architectural distortion - these changes are more marked in SFS (small for size) grafts. Also, due to hepatic arterial buffer response, reduced flow in hepatic artery leads to further ischemic injury, cholestasis and ischemic cholangitis. A recipient portal venous flow of \\> 250 ml/min/100 grams of liver weight is defined as portal hyper perfusion.\n\nH Y Ou et al retrospectively analysed data involving patients whose PVF \\> 250 ml/min/100 gr after reperfusion where 6 patients underwent inflow modulation (using splenic artery ligation) and other 2 didn't. They found that only 1 / 6 patients in those who underwent GIM developed SFSS where as both the patients who didn't undergo GIM developed SFSS (1 of them died). Also, none of the patients developed complications related to splenic artery ligation in their study.\n\nBhavin B et al in their retrospective study on 134 liver transplant recipients found that 19 patients met criteria for SFSS (as per Kyushu University). On analysis of the factors responsible for early graft dysfunction, only portal vein flow \\> 190 ml/min/100 gr of liver after reperfusion was found to be a significant predictor. GRWR was not significantly associated with graft dysfunction - 3 / 19 patients had GRWR \\< 0.8 while 16 patients in non-dysfunction group had GRWR \\< 0.8\n\nOgura et al retrospectively analysed data involving intentional portal pressure modulation when PVP (portal venous pressure) \\> 20 mm Hg. They found that the patients with a portal pressure \\< 15 mm Hg had better 2 year survival compared to those with \\> 15 mm Hg. Also, recovery from hyper bilirubinaemia and coagulopathy after transplantation was significantly better in those with PVP \\< 15 mm Hg.\n\nWang et al retrospectively analysed data involving 276 patients where they performed GIM by doing splenectomy (SPL) when PVP \\> 20 mm Hg. Group 1 had 134 patients who underwent SPL and Group 2 had 122 patients in whom GIM was not done. Graft compliance, Portal venous flow was significantly better in group 1 patients. Also, there was faster normalisation of bilirubin and ascites in group 1 when compared to group 2. Overall, 15.6 % patients had complications related to SPL - bleeding from splenic hilum, pancreatic leak, OPSS (overwhelming post spleenectomy sepsis) (1.9%).\n\nLuca A et al in their study involving cirrhotic patients with portal hypertension, splenic artery occlusion causes a significant reduction in portal pressure gradient (PPG). This drop was indirectly related to liver volume and directly related to spleen volume. The spleen/liver volume ratio\\> 0.5 accurately predicts the drop in PPG and may be used to identify patients who can obtain a significant advantage from procedures decreasing splenic inflow.\n\nAyman et al had done a study wherethey aimed to keep final PVP \\< 20 mm Hg and analysed if PVP \\> 15 is a better predictor than PVP \\> 20 mm Hg for SFSS. Peak bilirubin, INR, incidence of post-transplant HE and SFSS was significantly higher in those with PVP of 15 - 19 mm Hg (group B) vs in those with PVP \\< 15 mm Hg (group A). 90 day morbidity and mortality was also significantly higher in Group B when compared to group A. On comparing grafts with GRWR \\< 0.8 with \\> 0.8, no significant differences in postoperative outcomes were seen.\n\nTroisi et al did a retrospective study where they used Splenic artery ligation as the method of GIM when Recipient Portal Venous Flow was three times that of Donor portal vein flow. Group 1 had 11 patients with no GIM and group 2 had 13 patients who underwent GIM. SFSS occurred in three patients in Group 1 where all three needed re-transplantation whereas none of the patients in Group 2 developed SFSS. Also, One-year overallsurvival was 62% and 93% respectively for Group 1 and Group 2."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Portal Venous Pressure (PVP) \\> 15 mm Hg after reperfusion or\n* Portal venous flow (PVF) \\> 250 ml/min/100 gr of liver after reperfusion with a gradient (PVP - CVP) of ≥ 7 mm Hg\n\nExclusion Criteria:\n\n* Significant peripancreatic collaterals preventing safe access to splenic artery\n* Acute Liver Failure as an indication for transplant\n* ABO incompatible transplants\n* Pediatric transplants\n* Refusal to participate in the study'}, 'identificationModule': {'nctId': 'NCT04252794', 'briefTitle': 'Graft Inflow Modulation for Portal Hyper-perfusion in Live Donor Liver Transplantation', 'organization': {'class': 'OTHER', 'fullName': 'Institute of Liver and Biliary Sciences, India'}, 'officialTitle': 'Graft Inflow Modulation for Portal Hyper-perfusion in Live Donor Liver Transplantation: a Randomized Pilot Study', 'orgStudyIdInfo': {'id': 'ILBS-Liver Transplant-02'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Patients who undergo GIM', 'description': 'If inclusion criteria are met, after randomisation, these group of patients will undergo splenic artery ligation (graft inflow modulation)', 'interventionNames': ['Procedure: Splenic artery ligation']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'No splenic artery ligation', 'description': 'If inclusion criteria are met, after randomisation, these group of patients will not undergo splenic artery ligation (graft inflow modulation)', 'interventionNames': ['Other: No intervention']}], 'interventions': [{'name': 'Splenic artery ligation', 'type': 'PROCEDURE', 'description': 'Splenic artery will be ligated just after takeoff from coeliac trunk at the level of body of pancreas', 'armGroupLabels': ['Patients who undergo GIM']}, {'name': 'No intervention', 'type': 'OTHER', 'description': 'Splenic artery is not ligated despite the presence of portal hyperperfusion', 'armGroupLabels': ['No splenic artery ligation']}]}, 'contactsLocationsModule': {'locations': [{'zip': '110074', 'city': 'New Delhi', 'country': 'India', 'facility': 'Institute of Liver and Biliary Sciences', 'geoPoint': {'lat': 28.62137, 'lon': 77.2148}}], 'overallOfficials': [{'name': 'Gattu Tharun, MS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Senior resident, Department of HPB surgery, ILBS, India'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Institute of Liver and Biliary Sciences, India', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Senior Resident, HPB Surgery', 'investigatorFullName': 'Gattu Tharun', 'investigatorAffiliation': 'Institute of Liver and Biliary Sciences, India'}}}}