Impact of Melatonin in the Pretreatment of Organ Donor and the Influence in the Evolution of Liver Transplant.

NCT01860716 | Unknown Phase 3 DMC

• 1 other identifier: PI10/02877
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Impact of melatonin on organ donor pretreatment and liver transplant recipient: prospective, randomized, double-blind trial. OBJECTIVES. To establish the efficacy of the melatonin administered to encephalic death donors (EDD) in liver transplantation. The aim is to improve the functional quality of the retrieved organs, attenuate lesions and ischemia-reperfusion mediators, and provide grafts with greater resistance to post-transplant aggression. METHODOLOGY. Prospective, randomized, double-blind, pilot trial to evaluate preconditioning with melatonin versus placebo in EDDs. Two groups, melatonin and control-placebo, n=30 per group. Administration to donor via NG tube of 30mg of melatonin or placebo (lactose) upon inclusion in the trial, 60 minutes prior to commencement of surgery and following laparotomy during extraction. Evaluation of response to treatment: A) Conventional clinical, hemodynamic, analytical and histopathological parameters in donor and recipient. B) Plasma determinations for: oxidative/nitrosative stress; acute phase proteins; cellular and humoral immunity; NT-proBNP and cystatin C; endocrine profile; melatonin levels. C) Determinations in liver tissue: quantification of malonyldialdehyde-4hydroxyalkenals and protein carbonyl content; cellular and mitochondrial membrane fluidity; markers of tissue-vascular damage and proliferation: transforming growth factor-beta (TGF-β); hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF). Data will be analyzed following a prospectively define plan and by intention-to-treat analysis.

Conditions

Evidence of Liver Transplantation

Keywords

Melatonin, liver transplant, oxidative stress

Outcome Measures

Primary Outcomes (4)

• AST levels

  Aspartate transaminase (AST) levels will be measured.

  Between days 1 and 10 postoperatively.

• ALT

  Alanine transaminase (ALT) levels will be measured.

  Between days 1 and 10 postoperatively

• Bilirubin levels

  Bilirubin levels will be measured.

  Between days 1 and 10 postoperatively

• Prothrombin levels

  Prothrombin levels will be measured.

  Between days 1 and 10 postoperatively

Secondary Outcomes (6)

• Post-reperfusion syndrome

  Transplant day

• No primary function and primary graft dysfunction

  Transplant day

• Survival of the graft

  From day 0 to 3 months

• Patient survival

  Day 0 to 3 months

• Donor and recipient serological parameters

  Between days 1 and 10 postoperatively

Study Arms (2)

Solution for infusion

PLACEBO COMPARATOR

Solution for infusion administrated via nasogastric tube

Drug: Placebo

Melatonin

EXPERIMENTAL

30 mg melatonin administrated via nasogastric tube in the Intensive Care Unit when included in the study and 30 mg melatonin 60 minutes before transfer to the operating room.

Drug: Melatonin

Interventions

Melatonin DRUG

Melatonin 2 mg prolonged-release tablet, administration via nasogastric tube.

Also known as: Circadin (Neurim Pharmaceuticals)

Melatonin

Placebo DRUG

Solution for infusion

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A) Donors
• Encephalic-death (ED) organ donor who is situated in the ICUs of accredited hospitals in Zaragoza and meets each and every one of the following criteria.
• Being 16 years old or older.
• Informed consent for the donation signed by the immediate family.
• Receive intensive treatment and standard maintenance of the donor in ED, in accordance with universally accepted protocols of the Organizacion Nacional de Trasplantes (ONT), of the Aragon Autonomous Transplant Coordination, and of the ICUs and the participating hospitals in the study.
• B) Liver transplant recipients
• Being 18 years old or older and being less than 68 years of age.
• Informed consent for the procedure of LT signed.

You may not qualify if:

• A) Donors
• A potential encephalic-death organ donor will not be included in the study if either of the following criteria:
• No standard concomitant treatment and management of donor in ED.
• B) Liver transplant recipients
• Split, domino or multiorgan transplantation.
• Grafts removed by other surgical teams.
• Pregnant women or fertile not using contraceptive measures highly effective.

Sponsors & Collaborators

• Aragon Institute of Health Sciences: lead
• Fondo de Investigacion Sanitaria: collaborator

Study Sites (1)

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Zaragoza, 50009, Spain

Location

MeSH Terms

Interventions

Melatonin

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Francisco A. García-Gil, Physician

  Hospital Clínico Universitario Lozano Blesa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2013
• First Posted: May 23, 2013
• Study Start: May 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: May 23, 2013

Record last verified: 2013-05

Locations

ES (1)