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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by University Hospital, Ghent
Sponsor:
Information provided by (Responsible Party):
University Hospital, Ghent
ClinicalTrials.gov Identifier:
NCT01290172
First received: February 3, 2011
Last updated: February 1, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Liver Transplant With Clinically Significant Portal Hypertension
Drug: Administration of Somatostatin
Drug: Administration of placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Single-center, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Somatostatin Used as Inflow Modulator in Liver Transplantation.

Resource links provided by NLM:


Further study details as provided by University Hospital, Ghent:

Primary Outcome Measures:
  • Evaluation of safety and efficacy using Somatostatin. [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • To elucidate pathophysiological pathways in non-cirrhotic grafted livers. [ Time Frame: 35 days ] [ Designated as safety issue: No ]
  • To evaluate the reduction of ischemia-reperfusion injury (cytoprotective effect) [ Time Frame: 1 hour after reperfusion and 5 days ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: December 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Somatostatin
Patients in this group receive treatment with Somatostatin for 5 days.
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.

Placebo Comparator: Placebo
Patients in this group receive a placebo 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.


  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01290172

Contacts
Contact: Roberto Troisi, PhD, MD Roberto.Troisi@ugent.be

Locations
Belgium
University Hospital, Ghent Recruiting
Ghent, Belgium, 9000
Contact: Roberto Troisi, MD, PhD         
Sub-Investigator: Mauricio Sainz-Barriga, MD         
Principal Investigator: Roberto Troisi, PhD, MD         
Sponsors and Collaborators
University Hospital, Ghent
Investigators
Principal Investigator: Roberto Troisi, PhD, MD University Hospital, Ghent
  More Information

Additional Information:
No publications provided

Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT01290172     History of Changes
Other Study ID Numbers: 2008/689, 2008-008319-24
Study First Received: February 3, 2011
Last Updated: February 1, 2013
Health Authority: Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by University Hospital, Ghent:
Liver transplant
portal hypertension

Additional relevant MeSH terms:
Hypertension
Hypertension, Portal
Vascular Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases
Somatostatin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014