Clinical trial NCT01860716: Impact of Melatonin in the Pretreatment of Organ Donor and the Influence in the Evolution of Liver Transplant.
Official title: Impact of Melatonin in the Pretreatment of Organ Donor and the Influence in the Evolution of Liver Transplant: a Prospective, Randomised Double-blind Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Evidence of Liver Transplantation
Keywords: Melatonin, liver transplant, oxidative stress
Lead sponsor: Aragon Institute of Health Sciences
Sponsor class: OTHER
Collaborators: name: Fondo de Investigacion Sanitaria
First posted: 2013-05-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: This study will be done in the Hospital Clinico Lozano Blesa (Zaragoza, Spain), promoted by the Health Science Aragon Institute and its principal investigator is F. Agustín García Gil (Surgical Service). It will start in April-May 2013 and will finish 12 months later approximately. The study sponsor is I+CS (Aragon Institute of Health Sciences).

Eligibility criteria: Inclusion Criteria:

A) Donors

1. 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.
2. Being 16 years old or older.
3. Informed consent for the donation signed by the immediate family.
4. Informed consent for inclusion of the donor in the study .
5. 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

1. Being 18 years old or older and being less than 68 years of age.
2. Informed consent for the procedure of LT signed.
3. Informed consent for patient inclusion in the study, signed the same day that consent to the LT.

Exclusion Criteria:

A) Donors

A potential encephalic-death organ donor will not be included in the study if either of the following criteria:

1. Absence of either signed informed consent: for organ donation or for inclusion in the study.
2. No standard concomitant treatment and management of donor in ED.

B) Liver transplant recipients

1. Absence of either signed informed consent: for liver transplantation or for inclusion in the study.
2. Split, domino or multiorgan transplantation.
3. Grafts removed by other surgical teams.
4. Pregnant women or fertile not using contraceptive measures highly effective.

Primary outcomes:
measure: AST levels
timeFrame: Between days 1 and 10 postoperatively.
measure: ALT
timeFrame: Between days 1 and 10 postoperatively
measure: Bilirubin levels
timeFrame: Between days 1 and 10 postoperatively
measure: Prothrombin levels
timeFrame: Between days 1 and 10 postoperatively
Secondary outcomes:
measure: Post-reperfusion syndrome
timeFrame: Transplant day
measure: No primary function and primary graft dysfunction
timeFrame: Transplant day
measure: Survival of the graft
timeFrame: From day 0 to 3 months
measure: Patient survival
timeFrame: Day 0 to 3 months
measure: Donor and recipient serological parameters
timeFrame: Between days 1 and 10 postoperatively
measure: Morphological and functional quality of the liver graft evaluated by histological parameters of ischemia-reperfusion and tissue biochemical markers
timeFrame: Day 0 and day 1
Other outcomes:
Locations:
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
Study officials:
affiliation: Hospital Clínico Universitario Lozano Blesa
name: Francisco A. García-Gil, Physician
role: PRINCIPAL_INVESTIGATOR
References: