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

Evidence of Liver Transplantation Clinical Trial

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01860716
• Other study ID #: PI10/02877
• Status: Not yet recruiting
• Phase: Phase 3
• First received: May 17, 2013
• Last updated: May 22, 2013
• Start date: May 2013
• Est. completion date: December 2013

Study information

• Verified date: May 2013
• Source: Aragon Institute of Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 68 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Evidence of Liver Transplantation

Intervention

Drug:
• Melatonin
Melatonin 2 mg prolonged-release tablet, administration via nasogastric tube.
• Placebo

Locations

Country	Name	City	State
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Aragon Institute of Health Sciences	Fondo de Investigacion Sanitaria

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AST levels	Aspartate transaminase (AST) levels will be measured.	Between days 1 and 10 postoperatively.	No
Primary	ALT	Alanine transaminase (ALT) levels will be measured.	Between days 1 and 10 postoperatively	No
Primary	Bilirubin levels	Bilirubin levels will be measured.	Between days 1 and 10 postoperatively	No
Primary	Prothrombin levels	Prothrombin levels will be measured.	Between days 1 and 10 postoperatively	No
Secondary	Post-reperfusion syndrome	Post-reperfusion syndrome	Transplant day	No
Secondary	No primary function and primary graft dysfunction	No primary function and primary graft dysfunction	Transplant day	No
Secondary	Survival of the graft	Survival of the graft	From day 0 to 3 months	No
Secondary	Patient survival	Patient survival	Day 0 to 3 months	No
Secondary	Donor and recipient serological parameters	Donor and recipient serological parameters	Between days 1 and 10 postoperatively	No
Secondary	Morphological and functional quality of the liver graft evaluated by histological parameters of ischemia-reperfusion and tissue biochemical markers	Morphological and functional quality of the liver graft evaluated by histological parameters of ischemia-reperfusion and tissue biochemical markers	Day 0 and day 1	No