Mitochondrial Function in Septic Patients

NCT03748537 | Completed DMC

• 1 other identifier: EME-2559-04262
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Aim #1 To investigate the prevalence, risk and correlation of the level of sepsis with mitochondrial dysfunction in sepsis patients Aim 1.1 To investigate the prevalence of mitochondria dysfunction among sepsis patients Aim 1.2 To investigate the risk associated with mitochondrial dysfunction in sepsis patients. Aim 1.3 To investigate the association between sepsis severity (SOFA scoring system) and the degree of mitochondrial dysfunction Aim #2 To investigate the association of mitochondrial dysfunction in sepsis with ScvO2, lactate and ∆PCO2 Aim 3.1 To investigate the therapeutic efficacy of steroids on the improvement mitochondrial function in sepsis patients Aim 3.2. To investigate the efficacy of steroids on the reduction mortality rate in sepsis patients with norepinephrine-resistant hypotension

Conditions

Sepsis; Septic Shock

Outcome Measures

Primary Outcomes (3)

• To investigate the level of mitochondrial respiration after steroid administration

  Mean level comparative of mitochondrial respiration\* in "Hydrocortisone" and "No intervention" groups will be investigated at before, day 1 after and day 7 after administration of intervention. \*Mitochondrial function are mitochondrial respiration (Oxygen consumption rate in basal respiration, adenosine triphosphate (ATP) production, maximal respiration, spare capacity, proton leak, and non-mitochondrial respiration; Report in picomole/min)

  7 days

• To investigate the level of mitochondrial stress after steroid administration

  Mean level comparative of mitochondrial stress\* in "Hydrocortisone" and "No intervention" groups will be investigated at before, day 1 after and day 7 after administration of intervention. \*Mitochondrial stress (mass of superoxide per mitochondrial mass) and oxidative phosphorylation in each complex (densitometric analysis by western blot)

  7 days

• To evaluate survival in septic patients who have refractory shock after steroid administration

  Evaluate survival comparison in "Hydrocortisone" and "No intervention" groups. In 28 days survival and survival analysis until 28 day.

  28 days

Secondary Outcomes (5)

• To investigate risk factor (Age, underlying disease, number of organ dysfunction) correlation with the mitochondrial function in sepsis patients

  since emergency department admission until blood examination was collected, up to 24 hours.

• To investigate severity level of sepsis (SOFA Score) correlation with the mitochondrial function in sepsis patients

  since emergency department admission until blood examination was collected, up to 24 hours.

• To investigate the association of level of mitochondrial function in sepsis with central venous oxygen saturation (ScvO2)

  since emergency department admission until patient disposition form emergency department, up to 24 hours.

• To investigate the association of level of mitochondrial function in sepsis with serum lactate.

  since emergency department admission until patient disposition form emergency department, up to 24 hours.

• To investigate the association of level of mitochondrial function in sepsis with venous-to-arterial carbon dioxide tension difference (delta PCO2).

  since emergency department admission until patient disposition form emergency department, up to 24 hours.

Study Arms (2)

Hydrocortisone

EXPERIMENTAL

Hydrocortisone will be administered intravenously at 200 mg every 24 hours for 5 days, then tapered to a 50 mg intravenous bolus every 12 hours for days 6 to 8 and 50 mg every 24 hours for days 9 to 11, and then stopped.

Drug: Hydrocortisone

No Hydrocortisone

NO INTERVENTION

In control group, patient will not receive any corticosteroids for seven day after inclusion.

Interventions

Hydrocortisone DRUG

After resuscitation, hypoperfusion in the sepsis patients will be treated by fluid resuscitation and vasopressor. Some groups of patients may be not responsive to this treatment (MAP \<65 mmHg), administration of steroids to this group will be blindly randomized (treatment and control group). During resuscitation of septic shock patients with fluid resuscitation and vasopressors, some may not respond to treatment (MAP \< 65 mmHg). Patients who have shock refractory to fluid resuscitation and norepinephrine therapy for more than 0.5 mcg/kg/min will be blindly randomized to receive steroid (treatment group) or placebo (control group). Blood samples will be obtained to determine mitochondrial functioning before, at day 1 and day 7 after administration of study medications in both groups.

Also known as: Cortisol

Hydrocortisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (≥18 years of age)
• Diagnosis of sepsis within 1 hour after presentation to the emergency department: known or presumed infection and SOFA score \> 2 (table1)
• Norepinephrine-resistant hypotension (refractory hypotension and not response to norepinephrine dose ≥ 0.5 mcg/k/min)

You may not qualify if:

• Known pregnancy
• Primary diagnosis of:
• acute cerebral vascular event
• acute coronary syndrome
• acute cardiogenic pulmonary edema
• status asthmaticus
• major cardiac arrhythmia (as part of primary diagnosis)
• seizure
• drug overdose
• injury from burn or trauma
• Hemodynamic instability due to active hemorrhage
• Requirement for immediate surgery
• Do-Not-Attempt-Resuscitation (DNAR) order
• Advanced directives restricting implementation of the resuscitation protocol
• Transferred from another in-hospital setting

Sponsors & Collaborators

• Chiang Mai University: lead

Study Sites (1)

Emergency Department, Faculty of Medicine, Chaing Mai University

Chiang Mai, 50200, Thailand

Location

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• BORWON WITTAYACHAMNANKUL, MD

  Emergency Department, Medicine Faculty, Chiang Mai University, Thailand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Eligible patients for aim#3 will be randomly assigned in a 1:1 ratio of hydrocortisone and no hydrocortisone administration (control group), in a block of four patterns. Serum cortisol will be collected before administration. Hydrocortisone will be administered intravenously at 200 mg every 24 hours for 5 days, then tapered to a 50 mg intravenous bolus every 12 hours for days 6 to 8 and 50 mg every 24 hours for days 9 to 11, and then stopped. In control group, patient will not receive any corticosteroids for seven day after inclusion.

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: November 21, 2018
• Study Start: January 1, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: January 27, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)