Evaluation of Efficacy and Safety of Somatostatin Used as Inflow Modulator in Liver Transplantation.

Tracking Information
First Submitted Date ICMJE	February 3, 2011
First Posted Date ICMJE	February 4, 2011
Last Update Posted Date	December 2, 2014
Study Start Date ICMJE	December 2010
Actual Primary Completion Date	December 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 3, 2011)	Evaluation of safety and efficacy using Somatostatin. [ Time Frame: 5 days ]; To evaluate the safety and efficacy, using Somatostatin as portal vein flow and pressure modulator in liver transplantation in humans. Hepatic and systemic hemodynamic measurements will be recorded prior, during and after the bolus infusion of Somatostatin/Placebo during liver transplantation. Infusion of Somatostatin/Placebo will be continued for 5 days.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01290172 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 4, 2011)	To elucidate pathophysiological pathways in non-cirrhotic grafted livers. [ Time Frame: 35 days ]; To evaluate the reduction of ischemia-reperfusion injury (cytoprotective effect) [ Time Frame: 1 hour after reperfusion and 5 days ]; To evaluate the efficacy of Somatostatin in the prevention of the small-for-size syndrome (SFSS) in partial liver transplantation. [ Time Frame: after 35 days ]
Original Secondary Outcome Measures ICMJE; (submitted: February 3, 2011)	To elucidate pathophysiological pathways in non-cirrhotic grafted livers. [ Time Frame: 35 days ]; To evaluate the reduction of ischemia-reperfusion injury (cytoprotective effect) [ Time Frame: after 5 days ]; To evaluate the efficacy of Somatostatin in the prevention of the small-for-size syndrome (SFSS) in partial liver transplantation. [ Time Frame: after 35 days ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Evaluation of Efficacy and Safety of Somatostatin Used as Inflow Modulator in Liver Transplantation.
Official Title ICMJE	A Single-center, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Somatostatin Used as Inflow Modulator in Liver Transplantation.
Brief Summary	This study is a 5 day, single-center, randomized, double blind, placebo-controlled study to evaluate the efficacy and safety of Somatostatin used as inflow modulator in liver transplantation. Patient systemic and hepatic dynamics will be collected and recorded at predefined time-points. To evaluate the ischemia-reperfusion injury, it is planned to perform liver biopsies at two different time-points to compare the liver structure and proteomic variations.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Liver Transplant With Clinically Significant Portal Hypertension
Intervention ICMJE	Drug: Administration of Somatostatin 6 mg will be diluted in saline in a 60 cc syringe to be infused over 24 h (250 mcg/h). The treatment will be started during the hepatectomy phase, after 1st measurement of native arterial and portal flow and pressure and given a clinically significant portal hypertension (CSPH) with a hepatic venous pressure gradient (HVPG) >= 10 mmHg. 5 cc will be injected in 2 minutes as a single bolus of 500 mcg. Somatostatin will be given a second time at the beginning of the warm ischemia time as a continuous infusion of 250 mcg/h(infusion rate 2,5 cc/h). This will allow the time needed for reaching a stable plasma concentration at reperfusion and minimizing risks of secondary effects. After portal revascularization of the liver graft, a new measurement of portal flow and pressure will be performed. Provided a portal vein flow (PVF) >= 90 ml/min * 100 g LW, the remaining 55 cc will be infused for the following 22 h. 6 mg per day of continuous infusion will be continued for 5 days.; Drug: Administration of placebo The placebo treatment will be started during the hepatectomy phase, after the 1st measurement of native arterial and portal flow and pressure and given a clinically significant portal hypertension (CSPH) with a hepatic venous pressure gradient (HVPG) >= 10 mmHg. 5 cc of the 60 cc solution will be injected in 2 minutes as a single bolus of 500 mcg. The placebo will be given a 2nd time at the beginning of the warm ischemia time as a continuous infusion of 250 mcg/h (infusion rate 2,5 cc/h). This will allow the time needed for reaching a stable plasma concentration at reperfusion and minimizing risks of secondary effects. After portal revascularization of the liver graft, a new measurement of portal flow and pressure will be performed. Provided a portal vein flow (PVF) >= 90 ml/min * 100 gram LW, the remaining 55 cc will be infused for the following 22 h. 6 mg per day of continuous infusion will be continued everyday to complete 5 days of therapy.
Study Arms	Experimental: Somatostatin Patients in this group receive treatment with Somatostatin for 5 days. Intervention: Drug: Administration of Somatostatin; Placebo Comparator: Placebo Patients in this group receive a placebo for 5 days. Intervention: Drug: Administration of placebo
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 3, 2011)	33
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	January 2014
Actual Primary Completion Date	December 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Ability and willingness to provide written informed consent; Cirrhotic patients with established clinically significant portal hypertension (CSPH) defined as an increase in hepatic venous pressure gradient >= 10 mmHg; Recipients who are 18-70 years of age receiving a primary liver transplant from a brain dead donor or living donor; Whole liver grafts and partial liver grafts can be included Exclusion Criteria: Patients who are recipients of multiple solid organ transplants, or have previously received an organ or tissue transplant that may not be completely resolved by thrombectomy; HIV positive patients; Patients with known history of portal thrombosis or diagnosed at the time of transplantation that may not be completely resolved by thrombectomy.; Patients included in the preoperative assessment without a CSPH at the time of the first intraoperative measurement of portal pressure; Patients with low portal perfusion (=< 90 ml/min*100 g of LV) measured at the time of operation. Portal flows above this limit can be excluded in the eventuality that, after infusion, the portal perfusion falls below this limit; Patients with porto-pulmonary hypertension; Patients with known cardiac arrhythmias; Recipients of cardiac-dead donors; Fulminant hepatic failure patients
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 70 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Belgium
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01290172
Other Study ID Numbers ICMJE	2008/689; 2008-008319-24 ( EudraCT Number )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	University Hospital, Ghent
Study Sponsor ICMJE	University Hospital, Ghent
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Roberto Troisi, PhD, MD University Hospital, Ghent
PRS Account	University Hospital, Ghent
Verification Date	November 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP