Efficacy of Melatonin in Patients With Severe Sepsis or Septic Shock

Aragon Institute of Health Sciences

Status and phase: Unknown; Phase 3

Conditions: Severe Sepsis; Septic Shock

Treatments: Drug: Melatonin

Study type: Interventional

Funder types: Other

Identifiers

NCT01858909

TRA-172

Details and patient eligibility

About

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

Specifically:

1. 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.

2. To evaluate, waiting for reduction under the influence of the treatment with melatonin, :

   1. clinical - analytical parameters of sepsis;
   2. levels of cytokines;
   3. oxidative and nitrosative stress;
   4. acute-phase proteins (APP), specially of the ITIH4;
   5. immune response;
   6. 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.

Full 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).

Enrollment: 110 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Exclusion criteria

• Patient with more than 24 hours from the first documentation of organ dysfunction

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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110 participants in 2 patient groups, including a placebo group

Control

Placebo Comparator group

Description:

saline every 12 hours for 28 days

Melatonin

Experimental group

Description:

Oral 30mg/12hours melatonin 28 days

Treatment:

Drug: Melatonin