SepsisPhase 4NCT00368381

Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis

A Phase 4 study testing Hydrocortisone and Fludrocortisone in people with Sepsis and Adrenal Insufficiency, run by CAMC Health System.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

The purpose of this study is to determine if the combination of hydrocortisone plus fludrocortisone is more efficacious than hydrocortisone alone in treating adrenal insufficiency in severe sepsis. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Sepsis, Adrenal Insufficiency
What is being tested?: Hydrocortisone and Fludrocortisone
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: Sep 2006to Sep 2009
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Males and non-pregnant females > 18 years of age
Patients admitted and/or pending admission to the intensive care unit
Positive corticotropin stimulation test (Basal cortisol level of ≤ 34 μg/dL with Δ ≤ 9 μg/dL after administration of 250 mg of cosyntropin)
Patient satisfies criteria for severe sepsis Infection - one or more of the following criteria
Documented or Suspected - positive culture results (from blood, sputum, urine, etc.)
Anti-Infective Therapy - patient is receiving antibiotic, antifungal, or other anti-infective therapy

Show all 22Show fewer

Pneumonia - documentation of pneumonia (x-ray, etc.)
WBCs - WBCs found in normally sterile .uid (urine, CSF, etc.)
Perforated Viscus - perforation of hollow organ (bowel)
SIRS - two or more of the following
Temperature > 38° or < 36°
Heart rate > 90 bpm
Respiratory rate above 20 breaths per minute
WBC > 14,000/mm3 , < 4000/mm3, or >10% Bands
Acute organ dysfunction - one or more of the following
Cardiovascular - SBP < 90 mmHg or MAP < 70 mmHg despite 20 mL/kg of fluid resuscitation
Respiratory - PaO2/FiO2 ratio < 250, PEEP > 7.5, or require mechanical ventilation
Renal - low urine output (eg, <0.5 mL/kg/hr for 1 hour despite 20mL/kg of fluid resuscitation, increased creatinine (>50% increase from baseline) or require acute dialysis
Hematologic - low platelet count (< 100,000/mm3) or PT/PTT > upper limit of normal
Metabolic - low pH with high lactate (eg, pH < 7.30 and plasma lactate > upper limit of normal
Hepatic - liver enzymes > 2x upper limit of normal
CNS - altered consciousness or reduced Glasgow Coma Score

Who cannot join

Patients who respond to the short cosyntropin stimulation test(Δ > 9mg/dL)
Pregnancy or breast-feeding mother
Evidence of acute myocardial infarction, meningitis, pulmonary embolism
AIDS (CD4 < 200 cells/mL)
Contraindications for corticosteroids
Formal indication for corticosteroids (specifically including patients with known adrenal insufficiency)

Show all 9Show fewer

Onset of shock > 24 hours
Etomidate administration within the 6 hours preceding randomization
Cardiac arrest prior to randomization.

About this study

Official title: A Blinded, Placebo Controlled Trial of Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis

The purpose of this study is to determine if the combination of hydrocortisone plus fludrocortisone is more efficacious than hydrocortisone alone in treating adrenal insufficiency in severe sepsis.

Read the detailed description

Sepsis is a significant cause of morbidity and mortality in critically ill patients in the United States. As evidenced by its increasing prevalence and high mortality rates, sepsis is a complex and difficult syndrome to treat. Current therapeutic management of sepsis includes fluid resuscitation, vasopressor and inotropic support, maintenance of oxygen delivery, drotrecogin alpha, and steroid replacement therapy in patients who are found to have adrenal insufficiency. Studies in septic patients suggest that the administration of stress doses of hydrocortisone alone, or the combination of hydrocortisone plus fludrocortisone promotes an improvement in cardiovascular performance and a quicker resolution of shock symptoms. Current therapeutic guidelines for the treatment of severe sepsis recommend either hydrocortisone alone or combination therapy with hydrocortisone and fludrocortisone as therapeutic options for the treatment of adrenal dysfunction in severe sepsis. This study will help determine which regimen is more efficacious in this patient population.

Conditions: Sepsis, Adrenal Insufficiency
Being tested: Hydrocortisone, Fludrocortisone
Keywords: sepsis, septicemia, sepsis syndrome, adrenal insufficiency, adrenal cortex hormones, hydrocortisone, fludrocortisone
Medical subject headings: Sepsis, Adrenal Insufficiency, Systemic Inflammatory Response Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

HydrocortisoneDrug
Hydrocortisone administered for the treatment of adrenal insufficiency in participants with severe sepsis.
FludrocortisoneDrug
Fludrocortisone administered in combination with hydrocortisone for the treatment of adrenal insufficiency in participants with severe sepsis.

Study groups in NCT00368381
Study group	Role	What they receive
Hydrocortisone	Active comparator	Participants with adrenal insufficiency associated with severe sepsis were treated with hydrocortisone therapy to evaluate the efficacy of hydrocortisone alone in the treatment of adrenal insufficiency. Receives: Drug: Hydrocortisone
Hydrocortisone Plus Fludrocortisone	Active comparator	Participants with adrenal insufficiency associated with severe sepsis were treated with combination therapy consisting of hydrocortisone and fludrocortisone to determine whether the addition of fludrocortisone improved treatment efficacy. Receives: Drug: Hydrocortisone; Drug: Fludrocortisone

What is being measured

The primary outcome is the main question the study is designed to answer.

All cause mortality
All cause mortality during first 28-days after study randomization.
Measured: 28 days

Secondary outcomes (1)

Intensive care unit survival, duration of intensive care unit stay, duration of hospitalization, survival to hospital discharge, time to vasopressor withdrawal
The various secondary endpoints are patient specific serrogate markers of improvement in clinical status. Time frame for these endpoints to occur is patient specific and can not be defined for the entire study population.
Measured: Unable to define

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2006Sep 2009

First posted24 Aug 2006 (estimated)
Study startSep 2006
Primary completionJul 2009
Study completionSep 2009

Why it stopped: Study closed for PI failure to submit renewal paperwork

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (27)Papers the sponsor has linked to this study.
Other trials for SepsisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00368381
Sponsor's protocol ID: 06-05-1813
Status last verified: Feb 2012
First submitted: 23 Aug 2006
Last updated: 31 Aug 2026
Results posted: No
Data monitoring committee: No

Publications

Balk RA. Severe sepsis and septic shock. Definitions, epidemiology, and clinical manifestations. Crit Care Clin. 2000 Apr;16(2):179-92. doi: 10.1016/s0749-0704(05)70106-8.
PubMed 10768078
Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001 Aug 23;345(8):588-95. doi: 10.1056/NEJMra002709. No abstract available.
PubMed 11529214
Dellinger RP. Cardiovascular management of septic shock. Crit Care Med. 2003 Mar;31(3):946-55. doi: 10.1097/01.CCM.0000057403.73299.A6. No abstract available.
PubMed 12627010
Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. doi: 10.1056/NEJMra021333. No abstract available.
PubMed 12519925
Vincent JL, Abraham E, Annane D, Bernard G, Rivers E, Van den Berghe G. Reducing mortality in sepsis: new directions. Crit Care. 2002 Dec;6 Suppl 3(Suppl 3):S1-18. doi: 10.1186/cc1860. Epub 2002 Dec 5.
PubMed 12720570
Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002 Jan 9;287(2):236-40. doi: 10.1001/jama.287.2.236. No abstract available.
PubMed 11779267
Lamberts SW, Bruining HA, de Jong FH. Corticosteroid therapy in severe illness. N Engl J Med. 1997 Oct 30;337(18):1285-92. doi: 10.1056/NEJM199710303371807. No abstract available.
PubMed 9345079
Marik PE, Zaloga GP. Adrenal insufficiency in the critically ill: a new look at an old problem. Chest. 2002 Nov;122(5):1784-96. doi: 10.1378/chest.122.5.1784.
PubMed 12426284
Annane D. Corticosteroids for septic shock. Crit Care Med. 2001 Jul;29(7 Suppl):S117-20. doi: 10.1097/00003246-200107001-00036.
PubMed 11445745
Williamson DR, Lapointe M. The hypothalamic-pituitary-adrenal axis and low-dose glucocorticoids in the treatment of septic shock. Pharmacotherapy. 2003 Apr;23(4):514-25. doi: 10.1592/phco.23.4.514.32123.
PubMed 12680481
Shenker Y, Skatrud JB. Adrenal insufficiency in critically ill patients. Am J Respir Crit Care Med. 2001 Jun;163(7):1520-3. doi: 10.1164/ajrccm.163.7.2012022. No abstract available.
PubMed 11401866
Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. 2003 Feb 20;348(8):727-34. doi: 10.1056/NEJMra020529. No abstract available.
PubMed 12594318
Barber AE, Coyle SM, Fischer E, Smith C, van der Poll T, Shires GT, Lowry SF. Influence of hypercortisolemia on soluble tumor necrosis factor receptor II and interleukin-1 receptor antagonist responses to endotoxin in human beings. Surgery. 1995 Aug;118(2):406-10; discussion 410-1. doi: 10.1016/s0039-6060(05)80352-6.
PubMed 7638758
van der Poll T, Barber AE, Coyle SM, Lowry SF. Hypercortisolemia increases plasma interleukin-10 concentrations during human endotoxemia--a clinical research center study. J Clin Endocrinol Metab. 1996 Oct;81(10):3604-6. doi: 10.1210/jcem.81.10.8855809.
PubMed 8855809
Bone RC, Fisher CJ Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med. 1987 Sep 10;317(11):653-8. doi: 10.1056/NEJM198709103171101.
PubMed 3306374

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Sepsis trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Blinded, Placebo Controlled Trial of Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis
ClinicalTrials.gov ID: NCT00368381
Acronym / sponsor ID: 06-05-1813
Conditions: Sepsis, Adrenal Insufficiency
Keywords: sepsis, septicemia, sepsis syndrome, adrenal insufficiency, adrenal cortex hormones, hydrocortisone, fludrocortisone
Phase: Phase 4
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Study closed for PI failure to submit renewal paperwork
Enrolment: 0 participants (actual)
Lead sponsor: CAMC Health SystemUniversity, hospital or other
Study start: Sep 2006
Primary completion: Jul 2009 (actual)
Study completion: Sep 2009 (actual)
First posted: 24 Aug 2006 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to determine if the combination of hydrocortisone plus fludrocortisone is more efficacious than hydrocortisone alone in treating adrenal insufficiency in severe sepsis.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Hydrocortisone	Active comparator	Drug: HydrocortisoneParticipants with adrenal insufficiency associated with severe sepsis were treated with hydrocortisone therapy to evaluate the efficacy of hydrocortisone alone in the treatment of adrenal insufficiency.
Hydrocortisone Plus Fludrocortisone	Active comparator	Drug: Hydrocortisone, Drug: FludrocortisoneParticipants with adrenal insufficiency associated with severe sepsis were treated with combination therapy consisting of hydrocortisone and fludrocortisone to determine whether the addition of fludrocortisone improved treatment efficacy.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

Males and non-pregnant females > 18 years of age
Patients admitted and/or pending admission to the intensive care unit
Positive corticotropin stimulation test (Basal cortisol level of ≤ 34 μg/dL with Δ ≤ 9 μg/dL after administration of 250 mg of cosyntropin)
Patient satisfies criteria for severe sepsis Infection - one or more of the following criteria
Documented or Suspected - positive culture results (from blood, sputum, urine, etc.)

Key exclusion criteria (9 listed)

Patients who respond to the short cosyntropin stimulation test(Δ > 9mg/dL)
Pregnancy or breast-feeding mother
Evidence of acute myocardial infarction, meningitis, pulmonary embolism
AIDS (CD4 < 200 cells/mL)
Contraindications for corticosteroids

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
HydrocortisoneHydrocortisone administered for the treatment of adrenal insufficiency in participants with severe sepsis.	Drug	Hydrocortisone, Hydrocortisone Plus Fludrocortisone
FludrocortisoneFludrocortisone administered in combination with hydrocortisone for the treatment of adrenal insufficiency in participants with severe sepsis.	Drug	Hydrocortisone Plus Fludrocortisone

Primary outcome

All cause mortality
Time frame: 28 days
All cause mortality during first 28-days after study randomization.

1 secondary outcome

Intensive care unit survival, duration of intensive care unit stay, duration of hospitalization, survival to hospital discharge, time to vasopressor withdrawal
Time frame: Unable to define

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
Background: PubMed 10768078Balk RA. Severe sepsis and septic shock. Definitions, epidemiology, and clinical manifestations. Crit Care Clin. 2000 Apr;16(2):179-92. doi: 10.1016/s0749-0704(05)70106-8.
Background: PubMed 11529214Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001 Aug 23;345(8):588-95. doi: 10.1056/NEJMra002709. No abstract available.
Background: PubMed 12627010Dellinger RP. Cardiovascular management of septic shock. Crit Care Med. 2003 Mar;31(3):946-55. doi: 10.1097/01.CCM.0000057403.73299.A6. No abstract available.
Background: PubMed 12519925Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. doi: 10.1056/NEJMra021333. No abstract available.
Background: PubMed 12720570Vincent JL, Abraham E, Annane D, Bernard G, Rivers E, Van den Berghe G. Reducing mortality in sepsis: new directions. Crit Care. 2002 Dec;6 Suppl 3(Suppl 3):S1-18. doi: 10.1186/cc1860. Epub 2002 Dec 5.
Background: PubMed 11779267Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002 Jan 9;287(2):236-40. doi: 10.1001/jama.287.2.236. No abstract available.
Background: PubMed 9345079Lamberts SW, Bruining HA, de Jong FH. Corticosteroid therapy in severe illness. N Engl J Med. 1997 Oct 30;337(18):1285-92. doi: 10.1056/NEJM199710303371807. No abstract available.
Background: PubMed 12426284Marik PE, Zaloga GP. Adrenal insufficiency in the critically ill: a new look at an old problem. Chest. 2002 Nov;122(5):1784-96. doi: 10.1378/chest.122.5.1784.
Background: PubMed 11445745Annane D. Corticosteroids for septic shock. Crit Care Med. 2001 Jul;29(7 Suppl):S117-20. doi: 10.1097/00003246-200107001-00036.
Background: PubMed 12680481Williamson DR, Lapointe M. The hypothalamic-pituitary-adrenal axis and low-dose glucocorticoids in the treatment of septic shock. Pharmacotherapy. 2003 Apr;23(4):514-25. doi: 10.1592/phco.23.4.514.32123.
Background: PubMed 11401866Shenker Y, Skatrud JB. Adrenal insufficiency in critically ill patients. Am J Respir Crit Care Med. 2001 Jun;163(7):1520-3. doi: 10.1164/ajrccm.163.7.2012022. No abstract available.
Background: PubMed 12594318Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. 2003 Feb 20;348(8):727-34. doi: 10.1056/NEJMra020529. No abstract available.

Related trials for Sepsis

Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
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Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
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Sepsis, Septic Shock

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

John A Bethea, Pharm.D. principal investigator

Charleston Area Medical Center (CAMC)

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Hydrocortisone and Fludrocortisone in people with Sepsis and Adrenal Insufficiency, run by CAMC Health System.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All cause mortality (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00368381, which also lists 27 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.