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

• Status: Terminated
• Trial end date: 2010-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Cleveland Clinic
• Treatments: Cortisol succinate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate

Criteria

Inclusion Criteria:Patients who meet the following criteria will be enrolled in the study:

• 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:

1. presence of increased number of PMNs (neutrophils) in normally sterile body fluid

2. positive culture or gram stain of blood, sputum, urine, or normally sterile body for a pathogenic microorganism

3. 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

4. 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

5. 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:

1. Core temperature either > 38°C (> 100.4°F) or < 36°C (< 96.8°F)

2. Tachycardia. Heart rate greater > 90 beats/minute

3. Respiratory rate > 20 b/min or PaCO2 < 32 torr, or need for mechanical ventilation due to sepsis

4. WBC > 12 or < 4 K/mm3

• End-organ cardiovascular dysfunction defined as hypotension unresponsive to fluid replacement necessitating vasopressor therapy, or lactate ≥4 mmol/L

Exclusion Criteria:

• 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