Hydrocortisone 50 mg Every 6 Hours Compared to Hydrocortisone 300 mg Per Day in Treatment of Septic Shock. (HSHC00582434)

Double Blinded, Randomized Trial, Comparing Intravenous Bolus of 50 mg of Hydrocortisone Every 6 Hours for 7 Days With a Continuous Infusion of 300 mg Per Day of Hydrocortisone 300-mg Group During 5 Days in the Treatment of Septic Shock.

We performed a multicenter, prospective, randomized, double-blind, pilot study in four adult medical intensive care units. Patients presenting septic shock were rapidly administered one of two regimens of hydrocortisone, either a 50-mg intravenous bolus every six hours during seven days (200-mg group) or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for five days (300-mg group). Hydrocortisone was stopped abruptly at the end of treatment.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Hydrocortisone hemisuccinate

Detailed Description

Hydrocortisone hemisuccinate (Hydrocortisone Upjohn) was supplied as a powder in 100 mg vials to be reconstituted with 2 ml of sterile water diluent. The placebo was saline serum supplied as 10 ml ampoules. The study drugs were administered according to two protocols. In the 200-mg group, patients received an intravenous bolus of 50 mg of hydrocortisone every six hours for seven days associated with a continuous infusion of placebo for five days. In the 300-mg group, patients received an initial bolus of 100 mg of hydrocortisone followed by a continuous infusion of 300 mg per day for five days associated with a bolus of placebo every six hours for seven days. In the two groups, hydrocortisone was stopped abruptly at the end of treatment. The investigators had the choice or resuming hydrocortisone at the end of the fifth day if deemed necessary.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients over 18 years old
• septic shock in accordance with the American College of Chest Physicians/Society of Critical Care Medicine Consensus Committee criteria. Septic shock was managed in accordance with the 2004 edition of the Surviving Sepsis Campaign guidelines.
• no minimal vasopressor dose was needed to enter the trial.

Exclusion Criteria:

• medical history of adrenal insufficiency
• ongoing corticosteroid treatment
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 200 mg group; Patients received an intravenous bolus of 50 mg of hydrocortisone every six hours for seven days associated with a continuous infusion of placebo for five days.	Drug: Hydrocortisone hemisuccinate; In the 200-mg group, patients received an intravenous bolus of 50 mg of hydrocortisone every six hours for seven days associated with a continuous infusion of placebo for five days. In the 300-mg group, patients received an initial bolus of 100 mg of hydrocortisone followed by a continuous infusion of 300 mg per day for five days associated with a bolus of placebo every six hours for seven days.; Other Names: Saline solution as placebo
Experimental: 300 mg group; Patients received an initial bolus of 100 mg of hydrocortisone followed by a continuous infusion of 300 mg per day for five days associated with a bolus of placebo every six hours for seven days.	Drug: Hydrocortisone hemisuccinate; In the 200-mg group, patients received an intravenous bolus of 50 mg of hydrocortisone every six hours for seven days associated with a continuous infusion of placebo for five days. In the 300-mg group, patients received an initial bolus of 100 mg of hydrocortisone followed by a continuous infusion of 300 mg per day for five days associated with a bolus of placebo every six hours for seven days.; Other Names: Saline solution as placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	The primary end point was to determine a difference in 28-day mortality between the 200-mg and 300-mg groups.	28-day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of permanent shock between groups	Permanent shock (PS) was defined as permanent catecholamine support (epinephrine or norepinephrine) in the ICU, from the onset of septic shock to death without a period of reversal.	28-day
Incidence of shock relapse between groups	Shock relapse (SR) was defined as recurrence of septic shock requiring catecholamine resumption.	28-day
Incidence of post hydrocortisone hemodynamic rebound between groups	Post hydrocortisone hemodynamic rebound (PHHR) was defined as SR within 48 hours after hydrocortisone cessation.	28-day
Incidence of adverse events between groups.	Incidences of hemorrhagic events, superinfections and the amount of needed insulin were compared between the two groups.	28-day

Collaborators and Investigators

• Sponsor: Association Niçoise de Réanimation Médicale
• Investigators: Principal Investigator: Gilles Bernardin, M.D., Association Niçoise de Réanimation Médicale

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: May 10, 2016
• First Submitted That Met QC Criteria: May 10, 2016
• First Posted (Estimate): May 11, 2016

Study Record Updates

• Last Update Posted (Estimate): May 23, 2016
• Last Update Submitted That Met QC Criteria: May 20, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Anti-Inflammatory Agents; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
• Other Study ID Numbers: 2007-005824-34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: The data are available for additional analysis