EBQ:CORTICUS Trial - Revision history

Danbot: Added Criticisms section

2026-03-21T22:39:03Z

Added Criticisms section

← Revisión anterior		Revisión del 22:39 21 mar 2026
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	# The Annane Trial used hydrocortisone plus the pure mineralocorticoid fludrocortisone and CORTICUS only used hydrocortisone		# The Annane Trial used hydrocortisone plus the pure mineralocorticoid fludrocortisone and CORTICUS only used hydrocortisone
	# In 2013 Boonen et al<ref>[http://www.nejm.org/doi/full/10.1056/NEJMoa1214969 Boonen E et al. "Reduced cortisol metabolism during critical illness." ''The New England Journal of Medicine.'' 2013;368:1477-1488.]</ref> in the NEJM questioned conventional plasma measurements of the cortisone during critical illness since there was a reduction in mediators of cortisol degradation in ICU patients. The ACTH stimulation test may be an inaccurate measurement of adrenal insufficiency during critical illness.		# In 2013 Boonen et al<ref>[http://www.nejm.org/doi/full/10.1056/NEJMoa1214969 Boonen E et al. "Reduced cortisol metabolism during critical illness." ''The New England Journal of Medicine.'' 2013;368:1477-1488.]</ref> in the NEJM questioned conventional plasma measurements of the cortisone during critical illness since there was a reduction in mediators of cortisol degradation in ICU patients. The ACTH stimulation test may be an inaccurate measurement of adrenal insufficiency during critical illness.

			==Criticisms==
			*Enrollment was slow (5 years), and the trial was underpowered due to difficulty reaching target enrollment
			*Patients were enrolled up to 72 hours after onset of septic shock, which is later than many clinicians would consider for steroid initiation
			*The study allowed open-label corticosteroid use at clinician discretion, potentially contaminating the control group
			*Sicker patients (higher APACHE II scores) may have been underrepresented compared to the Annane 2002 trial
			*Contradicted results of the earlier Annane trial, creating ongoing controversy about steroid use in septic shock

	==Funding==		==Funding==

JaredCWebb: /* Further Discussion */

2025-12-22T23:25:18Z

Further Discussion

← Revisión anterior		Revisión del 23:25 22 dic 2025
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	==Further Discussion==		==Further Discussion==
	* The authors note that they did not ~~each~~ their goal ~~enrollment~~ of 800 patients.		* The authors note that they did not reach their goal enrolment of 800 patients.

	*The CORTICUS trial questioned the outcome of the Annane Trial. Differences in the conclusions between the two trials may be due to		*The CORTICUS trial questioned the outcome of the Annane Trial. Differences in the conclusions between the two trials may be due to
Línea 98:		Línea 98:

	==Funding==		==Funding==
	~~Eu- ropean~~ Commission, the European Society of Intensive Care Medicine, the European Critical Care Research Network, the International Sepsis Forum, and the Gorham Foundation. Roche Diagnostics provided the Elecsys cortisol immunoassay		European Commission, the European Society of Intensive Care Medicine, the European Critical Care Research Network, the International Sepsis Forum, and the Gorham Foundation. Roche Diagnostics provided the Elecsys cortisol immunoassay

	==Sources==		==Sources==

Ostermayer: /* Criticisms */

2015-10-31T20:27:35Z

Criticisms

← Revisión anterior		Revisión del 20:27 31 oct 2015
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	:Hydrocortisone 3.9 vs. placebo 6.0 days (P=0.06)		:Hydrocortisone 3.9 vs. placebo 6.0 days (P=0.06)

	==~~Criticisms~~==		==Further Discussion==
	* The authors note that they did not each their goal enrollment of 800 patients.		* The authors note that they did not each their goal enrollment of 800 patients.

Ostermayer: /* Review Questions */

2015-10-31T20:27:18Z

Review Questions

@@ Línea 99: / Línea 99: @@
 ==Funding==
 Eu- ropean Commission, the European Society of Intensive Care Medicine, the European Critical Care Research Network, the International Sepsis Forum, and the Gorham Foundation. Roche Diagnostics provided the Elecsys cortisol immunoassay
 ==Sources==

Ostermayer: /* CME */

2014-04-03T14:44:57Z

CME

← Revisión anterior		Revisión del 14:44 3 abr 2014
Línea 100:		Línea 100:
	Eu- ropean Commission, the European Society of Intensive Care Medicine, the European Critical Care Research Network, the International Sepsis Forum, and the Gorham Foundation. Roche Diagnostics provided the Elecsys cortisol immunoassay		Eu- ropean Commission, the European Society of Intensive Care Medicine, the European Critical Care Research Network, the International Sepsis Forum, and the Gorham Foundation. Roche Diagnostics provided the Elecsys cortisol immunoassay

	==~~CME~~==		==Review Questions==
	<quiz display=simple>		<quiz display=simple>
	{Regarding hydrocortisone therapy for patients with septic shock, which of the following statements is true?		{Regarding hydrocortisone therapy for patients with septic shock, which of the following statements is true?

Ostermayer at 02:34, 30 March 2014

2014-03-30T02:34:14Z

← Revisión anterior		Revisión del 02:34 30 mar 2014
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	\| fulltexturl=http://www.nejm.org/doi/full/10.1056/NEJMoa071366		\| fulltexturl=http://www.nejm.org/doi/full/10.1056/NEJMoa071366
	\| pdfurl=http://www.nejm.org/doi/pdf/10.1056/NEJMoa071366		\| pdfurl=http://www.nejm.org/doi/pdf/10.1056/NEJMoa071366
			\| status= Complete
	}}		}}

Ostermayer: /* Funding */

2014-03-10T11:42:00Z

Funding

← Revisión anterior		Revisión del 11:42 10 mar 2014
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	==Funding==		==Funding==
	~~Supported by the European~~ Commission, the European Society of Intensive Care Medicine, the European Critical Care Research Network, the International Sepsis Forum, and the Gorham Foundation. Roche Diagnostics provided the Elecsys cortisol immunoassay.		Eu- ropean Commission, the European Society of Intensive Care Medicine, the European Critical Care Research Network, the International Sepsis Forum, and the Gorham Foundation. Roche Diagnostics provided the Elecsys cortisol immunoassay

	==CME==		==CME==
	<quiz display=simple>		<quiz display=simple>

Ostermayer: /* Outcome */

2014-03-10T11:41:14Z

Outcome

← Revisión anterior		Revisión del 11:41 10 mar 2014
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	==Outcome==		==Outcome==
	~~''Hydrocortisone vs. placebo.''~~

	===Primary Outcomes===		===Primary Outcomes===
	; 28-day mortality		; 28-day mortality
	: 34% vs. 32% (P=0.51)		: Hydrocortisone 34% vs. placebo 32% (P=0.51)

	===Secondary Outcomes===		===Secondary Outcomes===
	; Reversal of shock		; Reversal of shock
	: 76% vs. 70.4% (P=0.41)		: Hydrocortisone 76% vs. placebo 70.4% (P=0.41)

	; Time to reversal of shock		; Time to reversal of shock
	: 3.3 vs. 5.8 days (P<0.001)		: Hydrocortisone 3.3 vs. placebo 5.8 days (P<0.001)

	~~Other outcomes were not statistically different: length of stay, reversal of organ failure, rates of new infection, hypernatremia, hyperglycemia.~~

	===Subgroup analysis===		===Subgroup analysis===
	''Responsive to corticotropin''		''Responsive to corticotropin''
	; 28-day mortality		; 28-day mortality
	:39% vs. 36% (P=0.69)		:Hydrocortisone 39% vs. placebo 36% (P=0.69)
	; Reversal of shock		; Reversal of shock
	:94.7% vs. 76.5% (P=0.13)		:Hydrocortisone 94.7% vs. placebo 76.5% (P=0.13)
	; Time to reversal of shock		; Time to reversal of shock
	: 2.8 vs. 5.8 days (P<0.001)		: Hydrocortisone 2.8 vs. placebo 5.8 days (P<0.001)

	''Non-responsive to corticotropin''		''Non-responsive to corticotropin''
	; 28-day mortality		; 28-day mortality
	:29% vs. 29% (P=1.00)		:Hydrocortisone 29% vs. placebo 29% (P=1.00)
	; Reversal of shock		; Reversal of shock
	:79.7% vs. 74.2% (P=0.18)		:Hydrocortisone 79.7% vs. placebo 74.2% (P=0.18)
	; Time to reversal of shock		; Time to reversal of shock
	:3.9 vs. 6.0 days (P=0.06)		:Hydrocortisone 3.9 vs. placebo 6.0 days (P=0.06)

	==Criticisms==		==Criticisms==

Ostermayer at 11:36, 10 March 2014

2014-03-10T11:36:45Z

← Revisión anterior		Revisión del 11:36 10 mar 2014
Línea 23:		Línea 23:

	==Major Points==		==Major Points==
			This trial was performed to address the suggestion that there was a survival benefit with hydrocortisone and fludrocortisone administration to patients in septic shock with insufficiency <ref>Annane D, et al. "Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock". Journal of the American Medical Association. 2002. 288(7):862-871</ref>. The Annane Trial caused epiric corticosteroid administration to be the standard of care in patients with sepsis and resumed adrenal insufficiency.

			The Corticosteroid Therapy of Septic Shock (CORTICUS) trial randomized 499 patients with septic shock to hydrocortisone or placebo administration. Prior to treatment, all patients received an ACTH stimulation test and were classified as responders (cortisol rise >9 mcg/dL) or non-responders (cortisol rise ≤9 mcg/dL).

	== ~~2012~~ Guidelines==		In contrast to the Annane Trial, CORTICUS demonstrated that hydrocortisone does not improve survival in patients with septic shock, regardless of response to ACTH. While there was no survival benefit, hydrocortisone conferred a more rapid reversal of shock in all subgroups studied.


			==Current Guidelines==
			{{Sepsis Guidelines Steroids}}

	==Design==		==Design==
			* Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
			* N=499
			** Hydrocortisone (n=251)
			** Placebo (n=248)
			* Mean follow-up: 28 days

	==Inclusion Criteria==		==Inclusion Criteria==
			* Patients 18 years and older
			* All patients hospitalized in ICU
			* Septic shock (SBP<90 with 20cc/kg fluid replacement or vasopressors need for >1hr) or organ dysfunction attributable to sepsis

	===Exclusion Criteria===		===Exclusion Criteria===
			* Life expectancy <24h
			* Immunosuppression
			* Underlying disease with poor prognosis
			* Treatment with long-term corticosteroids within past 6 months or short-term corticosteroids within past 4 weeks

	==Interventions==		==Interventions==
			* Sixty minutes prior to administration of study drug, a high-dose (250mcg) ACTH-stimulation test was performed in all patients
			* Patients were classified as responsive (cortisol >9 mcg/dL) or non-responsive to ACTH (cortisol ≤9 mcg/dL)
			* Lastly patients were randomized to hydrocortisone 50mg or placebo IV q 6 hrs, tapered over a 6-day period


	==Outcome==		==Outcome==
			''Hydrocortisone vs. placebo.''

	===Primary Outcomes===		===Primary Outcomes===
			; 28-day mortality
			: 34% vs. 32% (P=0.51)

	===Secondary Outcomes===		===Secondary Outcomes===
			; Reversal of shock
			: 76% vs. 70.4% (P=0.41)

			; Time to reversal of shock
			: 3.3 vs. 5.8 days (P<0.001)

			Other outcomes were not statistically different: length of stay, reversal of organ failure, rates of new infection, hypernatremia, hyperglycemia.

	===Subgroup analysis===		===Subgroup analysis===
			''Responsive to corticotropin''
			; 28-day mortality
			:39% vs. 36% (P=0.69)
			; Reversal of shock
			:94.7% vs. 76.5% (P=0.13)
			; Time to reversal of shock
			: 2.8 vs. 5.8 days (P<0.001)

			''Non-responsive to corticotropin''
			; 28-day mortality
			:29% vs. 29% (P=1.00)
			; Reversal of shock
			:79.7% vs. 74.2% (P=0.18)
			; Time to reversal of shock
			:3.9 vs. 6.0 days (P=0.06)

	==Criticisms==		==Criticisms==
			* The authors note that they did not each their goal enrollment of 800 patients.

			*The CORTICUS trial questioned the outcome of the Annane Trial. Differences in the conclusions between the two trials may be due to
			# The Annane Trial's population was more critically ill
			# The Annane Trial’s enrollment occurring within 8 hours (vs. 72 hours in CORTICUS).
			# The Annane Trial used hydrocortisone plus the pure mineralocorticoid fludrocortisone and CORTICUS only used hydrocortisone
			# In 2013 Boonen et al<ref>[http://www.nejm.org/doi/full/10.1056/NEJMoa1214969 Boonen E et al. "Reduced cortisol metabolism during critical illness." ''The New England Journal of Medicine.'' 2013;368:1477-1488.]</ref> in the NEJM questioned conventional plasma measurements of the cortisone during critical illness since there was a reduction in mediators of cortisol degradation in ICU patients. The ACTH stimulation test may be an inaccurate measurement of adrenal insufficiency during critical illness.

	==Funding==		==Funding==
	Supported by the European Commission, the European Society of Intensive Care Medicine, the European Critical Care Research Network, the International Sepsis Forum, and the Gorham Foundation. Roche Diagnostics provided the Elecsys cortisol immunoassay.		Supported by the European Commission, the European Society of Intensive Care Medicine, the European Critical Care Research Network, the International Sepsis Forum, and the Gorham Foundation. Roche Diagnostics provided the Elecsys cortisol immunoassay.

	==CME==		==CME==
	<quiz display=simple>		<quiz display=simple>

Ostermayer at 01:49, 12 December 2013

2013-12-12T01:49:30Z

← Revisión anterior		Revisión del 01:49 12 dic 2013
Línea 13:		Línea 13:
	\| fulltexturl=http://www.nejm.org/doi/full/10.1056/NEJMoa071366		\| fulltexturl=http://www.nejm.org/doi/full/10.1056/NEJMoa071366
	\| pdfurl=http://www.nejm.org/doi/pdf/10.1056/NEJMoa071366		\| pdfurl=http://www.nejm.org/doi/pdf/10.1056/NEJMoa071366
	~~\| status=Complete~~
	}}		}}