Efficacy of Melatonin in Patients With Severe Sepsis or Septic Shock

Septic Shock Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01858909
• Other study ID #: TRA-172
• Status: Not yet recruiting
• Phase: Phase 3
• First received: May 17, 2013
• Last updated: May 17, 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

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.

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: 110
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Severe Sepsis
• Shock
• Shock, Septic
• Toxemia

Intervention

Drug:
• Melatonin
Administration via oral or via a nasogastric tube followed by 20mL saline

Locations

Country	Name	City	State
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Aragon Institute of Health Sciences	Ministerio de Sanidad, Servicios Sociales e Igualdad

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	Mortality at 28 days of study entry.	1 month	Yes
Primary	Clinical evolution parameters	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.	1 month	No
Secondary	Clinical evolution	clinical - analytical parameters relative to the sepsis	1 month	Yes
Secondary	Oxidative-nitrosative parameters	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	1 month	No
Secondary	Inflammatory parameters	Interleukins-1,2,4,5, 6, 7,8,10,12,13, IFN-?; TNF-a and GM-CSF	1 month	No
Secondary	Acute phase proteins	PCR, haptoglobin, Apo A-I, a1-GPA and ITIH4	1 month	No
Secondary	Immune parameters	Lymphocytes T, B, NK, T CD4, and T CD8, and immunoglobulins	1 month	No
Secondary	Endocrine parameters	Cortisol, aldosterone, ACTH, ADH, insulin, glucagon and 25-hydroxyvitamin D3	1 month	No