Efficacy of Melatonin in Patients With Severe Sepsis or Septic Shock

Sponsor

Aragon Institute of Health Sciences (Other)

Overall Status

Unknown status

CT.gov ID

NCT01858909

Collaborator

Ministerio de Sanidad, Servicios Sociales e Igualdad (Other)

110

Enrollment

Location

Arms

Duration (Months)

15.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

OBJECTIVES. To establish the therapeutic efficiency of melatonin in adult patients with severe sepsis and septic shock.

Specifically:

To evaluate the survival to 28 days of mechanical assisted ventilation, days with vasoactive drugs, need of hemodialysis-hemofiltration, superinfection and evolution towards the failure of other organs.
To evaluate, waiting for reduction under the influence of the treatment with melatonin, :
clinical - analytical parameters of sepsis;
levels of cytokines;
oxidative and nitrosative stress;
acute-phase proteins (APP), specially of the ITIH4;
immune response;
endocrine response.

METHODOLOGY. Patients will be randomized in two groups, n = 55 in each group: 1) treatment with melatonin 30mg/12 hours 28 days; 2) placebo.

Determinations: a) clinical - analytical parameters relative to the sepsis; b) melatonin plasmatic levels; c) quantification of malonyldialdehyde and 4-hydroxynonenal, protein carbonyl content, nitrites, erythrocyte membrane fluidity, and superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase activity; d) Interleukins-1,2,4,5, 6, 7,8,10,12,13, IFN-γ; TNF-α and GM-CSF; e) acute-phase proteins: PCR, haptoglobin, Apo A-I, α1-GPA and ITIH4; f) lymphocytes T, B, NK, T CD4, and T CD8, and immunoglobulins; g) cortisol, aldosterone, ACTH, ADH, insulin, glucagon and 25-hydroxyvitamin D3. Data will be analyzed following a prospectively define plan and by intention-to-treat (ITT) analysis.

Condition or Disease	Intervention/Treatment	Phase
Severe Sepsis Septic Shock	Drug: Melatonin	Phase 3

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Phase III, Prospective, Randomized, Double-blind Clinical Trial to Evaluate the Efficacy of Melatonin in Patients With Severe Sepsis or Septic Shock

Study Start Date :

May 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2013

Anticipated Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control saline every 12 hours for 28 days
Experimental: Melatonin Oral 30mg/12hours melatonin 28 days	Drug: Melatonin Administration via oral or via a nasogastric tube followed by 20mL saline Other Names: Liquid 1 mg/mL Melatonin

Arm

Intervention/Treatment

Placebo Comparator: Control

saline every 12 hours for 28 days

Experimental: Melatonin

Oral 30mg/12hours melatonin 28 days

Drug: Melatonin

Administration via oral or via a nasogastric tube followed by 20mL saline

Other Names:

Liquid 1 mg/mL Melatonin

Outcome Measures

Primary Outcome Measures

Mortality [1 month]
Mortality at 28 days of study entry.
Clinical evolution parameters [1 month]
Days of mechanical ventilation. Days with vasoactive drugs. Days with hemodialysis or hemofiltration. Superinfection of organs other than the initial cause of the sepsis. Progression to other organs fail after starting the treatment.

Secondary Outcome Measures

Clinical evolution [1 month]
clinical - analytical parameters relative to the sepsis
Oxidative-nitrosative parameters [1 month]
Melatonin plasmatic levels Quantification of malonyldialdehyde and 4-hydroxynonenal Protein carbonyl content Nitrites Erythrocyte membrane fluidity Superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase activity
Inflammatory parameters [1 month]
Interleukins-1,2,4,5, 6, 7,8,10,12,13, IFN-γ; TNF-α and GM-CSF
Acute phase proteins [1 month]
PCR, haptoglobin, Apo A-I, α1-GPA and ITIH4
Immune parameters [1 month]
Lymphocytes T, B, NK, T CD4, and T CD8, and immunoglobulins
Endocrine parameters [1 month]
Cortisol, aldosterone, ACTH, ADH, insulin, glucagon and 25-hydroxyvitamin D3

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients (males and females) over 18 years who meet the diagnostic criteria for severe sepsis or septic shock secondary to community-acquired pneumonia or hospital and or intra-abdominal infection