Septic Shock, Severe Sepsis
Conditions
Keywords
Sepsis
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).
Interventions
DRUGMelatonin
Administration via oral or via a nasogastric tube followed by 20mL saline
Sponsors
Ministerio de Sanidad, Servicios Sociales e Igualdad
Aragon Institute of Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Clinical evolution | 1 month | clinical - analytical parameters relative to the sepsis |
| Endocrine parameters | 1 month | Cortisol, aldosterone, ACTH, ADH, insulin, glucagon and 25-hydroxyvitamin D3 |
| Immune parameters | 1 month | Lymphocytes T, B, NK, T CD4, and T CD8, and immunoglobulins |
| 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 |
Countries
Spain
Outcome results
None listed