Hemodynamic and Inflammatory Effects of Abrupt Versus Tapered Corticosteroid Discontinuation in Septic Shock

NCT01150409 | Terminated Phase 4 Results DMC

• 1 other identifier: 08-336
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study will evaluate the potential benefit of a tapered course of hydrocortisone compared to abrupt cessation in patients initiated on hydrocortisone for septic shock. The study will include adult patients in the medical intensive care unit (MICU) who meet criteria for corticosteroid therapy for septic shock according to the current MICU protocol.All patients will receive 7 days of hydrocortisone (50mg/Q6hrs) as part of the routine management of septic shock, before being randomly assigned to receive hydrocortisone taper versus no taper. The primary study endpoint is the incidence of hypotension within 7 days after randomization. Secondary endpoints will include incidence of adrenal insufficiency, and changes in the inflammatory status (assessed by cytokine measurements) before, during, and after corticosteroid discontinuation. The cytokines to be measured include IL-1, IL-6, IL-9, IL-10, and TNF. Since there has not been a randomized clinical trial to investigate the potential benefit of weaning septic patients off low-dose hydrocortisone as opposed to stopping abruptly, this study has potential to change clinical practice by leading to a consistent approach of corticosteroid discontinuation and to a better understanding of their impact on the inflammatory modulation in septic shock.

Conditions

Septic Shock

Keywords

Sepsis; hydrocortisone

Outcome Measures

Primary Outcomes (1)

• Incidence of Hypotension Between Study Days 8 and 14 (Within 7 Days of the Initiation of Study Drug).

  Study screening/enrollment stopped due to lack of eligible subjects. No outcome measures were analyzed due to the low enrollment.

  Day 14

Study Arms (2)

hydrocortisone

EXPERIMENTAL

Hydrocortisone 50 mg IV every 12 hours x 4 doses (2 days), followed by Hydrocortisone 50 mg IV every 24 hours x 2 doses (2 days)

Drug: hydrocortisone; Drug: Normal Saline

Normal Saline (placebo)

PLACEBO COMPARATOR

0.9% sodium chloride (equal volume to hydrocortisone) IV every 12 hours x 4 doses (2-days), followed by 0.9% sodium chloride (equal volume to hydrocortisone) IV every 24 hours x 2 doses (2-days)

Drug: Normal Saline

Interventions

hydrocortisone DRUG

1\) Hydrocortisone 50 mg IV every 12 hours x 4 doses (2 days), followed by Hydrocortisone 50 mg IV every 24 hours x 2 doses (2 days)

Also known as: 11β,17α,21-trihydroxypregn-4-ene-3,20-dione

hydrocortisone

Normal Saline DRUG

0.9% sodium chloride (equal volume to hydrocortisone) IV every 12 hours x 4 doses (2-days), followed by 0.9% sodium chloride (equal volume to hydrocortisone) IV every 24 hours x 2 doses (2-days)

Also known as: 0.9% sodium chloride

Normal Saline (placebo); hydrocortisone

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• suspected septic shock
• initiation of hydrocortisone 50mg IV Q6H (per MICU protocol)
• written informed consent signed by patient or legal surrogate
• Septic shock is defined by meeting all of the following requirements:
• Clinical evidence of infection. Clinical evidence of infection is defined as the presence of a known or probable source of infection that has necessitated the initiation of systemic antimicrobial therapy. Clinical evidence of infection could include (but is not limited to) one or more of the following:
• presence of increased number of PMNs (neutrophils) in normally sterile body fluid
• positive culture or gram stain of blood, sputum, urine, or normally sterile body for a pathogenic microorganism
• chest radiograph consistent with a diagnosis of pneumonia with a positive culture, gram stain, diagnostic bronchoalveolar lavage, or protected specimen brush for a respiratory tract pathogen
• focus of infection identified by visual inspection (e.g., ruptured bowel found at surgery, wound with purulent drainage, radiographic or Computed tomographic evidence of an abscess or osteomyelitis, etc.) and
• patient has an underlying disease or condition that is highly likely to be associated with infection (e.g., ascending cholangitis, ischemic bowel, etc.)
• Two of the following:
• Core temperature either \> 38°C (\> 100.4°F) or \< 36°C (\< 96.8°F)
• Tachycardia. Heart rate greater \> 90 beats/minute
• Respiratory rate \> 20 b/min or PaCO2 \< 32 torr, or need for mechanical ventilation due to sepsis
• WBC \> 12 or \< 4 K/mm3

You may not qualify if:

• age less than 18
• previous systemic corticosteroid therapy in the past 90 days (prednisone \>5 mg/d or equivalent)
• pregnancy
• Acquired Immune Deficiency Syndrome (AIDS)
• hematological malignancies
• advanced form of cancer with less than 30-day life expectancy
• patients who receive fludrocortisone
• evidence of prior acute myocardial infarction

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Hydrocortisone; Saline Solution; Sodium Chloride

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; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Jorge Guzman MD
• Organization: The Cleveland Clinic Foundation

guzmanj@ccf.org

216-445-5765

Study Officials

• Jorge A Guzman, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2010
• First Posted: June 25, 2010
• Study Start: May 1, 2008
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: April 2, 2018
• Results First Posted: September 2, 2015

Record last verified: 2018-03

Locations

US (1)