Time course of hypothalamic-pituitary adrenal alterations in response to critical illness

• Register: ISRCTN
• Last refreshed on: 4 December 2018
• Main ID: ISRCTN98806770
• Date of registration: 30/12/2014
• Prospective Registration: No
• Primary sponsor: KU Leuven
• Public title: Time course of hypothalamic-pituitary adrenal alterations in response to critical illness
• Scientific title: On the dynamics of the hypothalamus-pituitary-adrenal axis response to prolonged critical illness: a prospective observational study
• Date of first enrolment: 01/12/2014
• Target sample size: 562
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN98806770
• Study type: Observational
• Study design: Observational cohort study (Other)

Countries of recruitment

Belgium

Contacts

• Name: Greet Van den Berghe

Key inclusion & exclusion criteria

Inclusion criteria:
For patients:
1. Critically ill patients admitted for =7 days to one of the five ICUs from two departments (medical and surgical) in the University Hospitals Leuven
2. Age =18 years

For healthy volunteers:
1. Age-, gender- and BMI-matched to the included patients

Exclusion criteria:
For patients:
1. Predisposing factors of adrenal insufficiency:
1.1. Cerebral disease with intracranial hypertension threatening the neuroendocrine system
1.2. Pituitary disorders including (pan)hypopituitarism
1.3. Known adrenal disease (Cushing's syndrome or Addison's disease)
1.4. Treatment with glucocorticoids, other steroids or anti-steroid chemotherapy within the last 3 months
1.5. Use of etomidate within the last 72 hours
1.6. Other drugs predisposing to adrenal insufficiency: azoles, phenytoin, rifampicin, glitazones, imipramin, phenothiazine, phenobarbital
2. No arterial line in place
3. Ethical restrictions:
3.1. Moribund
3.2. Declined participation

For healthy volunteers:
1. Recent history of treatment with HPA-axis interfering drugs


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Critical illness
Not Applicable

Intervention(s)

To evaluate the evolution of the HPA-axis alterations during critical illness, 24h-urine collection samples and blood samples (4 ml) will be collected daily in critically ill patients from day 7 until day 28 of their ICU stay to determine evolution of ACTH and cortisol plasma concentrations and urine cortisol metabolites. A short ACTH-stimulation test (injection of 250 µg Synacthen®) will be performed weekly. In patients staying more than 28 days, a minority of the ICU population, an additional blood sample (4 ml), 24 h urine collection and ACTH-stimulation test will be taken weekly until ICU discharge or death. On the last day in ICU an additional blood sample (4 ml) will be collected to quantify plasma ACTH and cortisol concentrations at recovery/death. After discharge from the ICU, a final blood sample and ACTH stimulation test will be taken on day 7 post-ICU or on the day of discharge in patients discharged from the hospital before day 7.

Primary Outcome(s)

1. Determination of the evolution of ACTH and cortisol plasma concentrations and urine cortisol metabolites during prolonged critical illness and upon recovery, in comparison with ACTH and cortisol plasma concentrations of healthy volunteers.
2. To characterize the time course of the response to exogenous ACTH during prolonged critical illness and upon recovery, in comparison with response to exogenous ACTH in healthy volunteers.

Secondary Outcome(s)

Further mechanistic analyses using clinical and laboratory parameters.

Secondary ID(s)

S57249

Source(s) of Monetary Support

Methusalem (long term structural funding by the Flemish Government, Belgium), Research Foundation - Flanders (FWO) (Belgium)

Ethics review

Status:
Approval date:
Contact:

Ethics Committee (Institutional Review Board) of the University Hospitals Leuven, 30/10/2014, ref: ML11107

Results

• Results available: Yes
• Date Completed: 31/07/2017