Effect of Hydrocortison on Post-ischemic Flow-mediated Dilation and on Thenar Oxygen Saturation in Human Septic Shock. (HyStOON)

Effect of Intravenous Hydrocortison on Post-ischemic Brachial Artery Dilation and on Thenar Oxygen Saturation in Adult Septic Shock. A Human Placebo-controlled Randomized Study.

The main objectives of the study are 1)to examine the immediate (2 hours) and delayed (8 hours) effects of intravenous hydrocortison on macro and microvascular post-ischemic vasoreactivity, in septic shock adult patients; 2) to examine possible correlations between post-ischemic flow-mediated dilation (FMD) of the brachial artery (assessed by ultrasound imaging) and post-ischemic recovery slope of the thenar oxygen saturation (StO2) (assessed by near-infrared spectroscopy).

Study Overview

• Status: Terminated
• Conditions: Septic Shock; Adult
• Intervention / Treatment: Drug: placebo followed by hydrocortisone hemisuccinate; Drug: hydrocortison hemisuccinate

Detailed Description

Two primary end points, considered as reflecting vasoreactivity will be assessed :

1. Flow-mediated dilation (FMD) of the brachial artery, measured by ultrasound imaging, expressed in mm or in percentage, will be calculated from artery diameters measured before and after a vascular occlusion test (cuff around arm or forearm).
2. recovery slope of thenar oxygen saturation (StO2), assessed by near infrared spectroscopy (NIRS), expressed in %/second, will be recorded after the vascular occlusion test.

The two primary end points (FMD and recovery slope of StO2)will be assessed at the following timepoints :

• baseline (before first injection of placebo or hydrocortison)
• 2 hours after first injection of placebo or hydrocortison
• 2 hours after second injection of placebo or hydrocortison (i.e. 8 hours after first injection)
• 4 to 6 hours after third injection
• 4 to 6 hours after fourth injection (optional)

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Orléans, France, 45000
    • Centre Hospitalier Regional D'Orleans

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:

• age over 18 yrs
• consent obtained
• septic shock (according to international definition)
• patient sedated and submitted to invasive mechanical ventilation
• no need for surgery expected within 24 hours after enrollment
• patient has received at least one dose of large spectrum antibiotics
• superior vena cava catheter in place
• patient carrying a thermodilution device for cardiac output measurement
• stable mean arterial pressure within 65-5 mmHg limits for at least 2 hours;

Exclusion Criteria:

• pregnancy
• age below 18 years
• patient treated with iv continuous epinephrine
• chronic occlusive arteriopathy of the upper limbs
• regular or recent treatment with glibenclamide or glipizide
• regular or recent treatment with steroids
• known surrenal insufficiency

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; 10 mL normal saline iv at H0 and H6 (2 first injections blinded), followed by hydrocortison (open label) 50 mg iv at H8, H14 and H20	Drug: placebo followed by hydrocortisone hemisuccinate
Active Comparator: hydrocortison; 50 mg hydrocortison iv at H0 and H6 (2 first injections blinded), followed by hydrocortison (open label) 50 mg iv at H12, H18 and H24	Drug: hydrocortison hemisuccinate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Vasoreactivity	every 6 hours over the first 24 hours of intervention

Collaborators and Investigators

• Sponsor: Centre Hospitalier Régional d'Orléans
• Investigators: Principal Investigator: Thierry Boulain, MD, Centre Hospitalier Régional d'Orléans, France

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2013
• Primary Completion (Actual): November 5, 2019
• Study Completion (Actual): November 5, 2019

Study Registration Dates

• First Submitted: March 20, 2013
• First Submitted That Met QC Criteria: March 20, 2013
• First Posted (Estimate): March 22, 2013

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

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: CHRO-2012-04; 2012-004736-39 (EudraCT Number)