Clinical trial NCT01858909: Efficacy of Melatonin in Patients With Severe Sepsis or Septic Shock
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Severe Sepsis
Septic Shock
Keywords: Sepsis
Lead sponsor: Aragon Institute of Health Sciences
Sponsor class: OTHER
Collaborators: name: Ministerio de Sanidad, Servicios Sociales e Igualdad
First posted: 2013-05-21
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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:

* 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

Primary outcomes:
measure: Mortality
timeFrame: 1 month
measure: Clinical evolution parameters
timeFrame: 1 month
Secondary outcomes:
measure: Clinical evolution
timeFrame: 1 month
measure: Oxidative-nitrosative parameters
timeFrame: 1 month
measure: Inflammatory parameters
timeFrame: 1 month
measure: Acute phase proteins
timeFrame: 1 month
measure: Immune parameters
timeFrame: 1 month
measure: Endocrine parameters
timeFrame: 1 month
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: