Septic ShockPhase 3COIITSSNCT00320099
Combination of Corticotherapy and Intensive Insulin Therapy for Septic Shock
A Phase 3 study testing recombinant human insulin, hydrocortisone and fludrocortisone in people with Septic Shock, run by University of Versailles at 8 sites in France.
Trial summary
This study will compare, in adults with septic shock, the safety and efficacy of a combination of moderate doses of corticosteroids and intensive insulin therapy to that of moderate doses of corticosteroids. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- recombinant human insulin, hydrocortisone and fludrocortisone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 508 participants
- Where
- 8 sitesFrance
- Study dates
- Jan 2006to Feb 2009
- Phase
- Phase 3
- 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
- Patients admitted in intensive care units for septic shock and meeting all following criteria
- Proven infection
- Need for vasopressor to maintain systemic arterial tension above 90 mmHg
- Multiple organ dysfunction as defined by a SOFA score ³ 8.
- Need for treatment with moderate dose of corticosteroids
Who cannot join
- One of the following :
- Pregnancy
- Less than 18 years old
- Moribund (i.e. expected to die on day of intensive care unit admission)
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
Hôpital Avicenne
Bobigny
Hôpital Jean Verdier
Bondy
CHU Grenoble
Grenoble
Hôpital central
Nancy
Hôpital Saint Louis
Paris, 75
Hôpital Bichat Claude Bernard
Paris
hôpital Cochin
Paris
Hôpital Delafontaine
Saint-Denis, 93
About this study
Official title: Phase 3 Study of Corticotherapy (Hydrocortisone Alone Versus Hydrocortisone Plus Fludrocortisone) Versus Corticotherapy Plus Intensive Insulin Therapy for Septic Shock
This study will compare, in adults with septic shock, the safety and efficacy of a combination of moderate doses of corticosteroids and intensive insulin therapy to that of moderate doses of corticosteroids. In addition, this study will compare the efficacy and safety of hydrocortisone alone versus hydrocortisone plus fludrocortisone
Read the detailed description
Objectives:
Comparison, in patients with septic shock, of efficacy and safety of the combination of moderate doses of corticosteroids and intensive insulin therapy to that of moderate doses of corticosteroids; and of efficacy and safety of hydrocortisone alone versus hydrocortisone plus fludrocortisone Methods
Study design :
This is a multicenter, prospective, randomised trial on parallel groups
Study treatments :
Experimental arm A:
A1=50 mg iv every 6 hours of hydrocortisone (hemisuccinate), 50µg through the nasogastric tube of 9 alpha fludrocortisone, for 7 days AND strict control of blood glucose levels with a target of 4,4 to 6 mmol/L using continuous iv infusion of insulin up to intensive care unit discharge.
A2=50 mg iv every 6 hours of hydrocortisone (hemisuccinate) for 7 days AND strict control of blood glucose levels with a target of 4,4 to 6 mmol/L using continuous iv infusion of insulin up to intensive care unit discharge.
Control arm B:
B1:50 mg iv every 6 hours of hydrocortisone (hemisuccinate), 50µg through the nasogastric tube of 9 alpha fludrocortisone, for 7 days.
B2:50 mg iv every 6 hours of hydrocortisone (hemisuccinate)for 7 days. Study Primary outcome : In-hospital mortality
Sample size calculation :
The expected in-hospital mortality rate in the control group is 50%. To detect an absolute reduction in in-hospital mortality rate of 12.5 %, that is 37.5% in the experimental arm versus 50% in the control arm, and considering risk alpha of 0,05 and a risk beta of 0,20, 254 patients per treatment arms are needed, for a total of 508 patients.
- Conditions
- Septic Shock
- Being tested
- recombinant human insulin, hydrocortisone, fludrocortisone
- Keywords
- septic shock, adrenal insufficiency, glucose control, mineralocorticoids
- Medical subject headings
- Shock, Septic, Adrenal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant human insulinDrug
intensive insulin therapy as a continuous infusion to maintain blood glucose levels between 4 and 6 mmol/l
hydrocortisoneDrug
50 mg as iv bolus every 6 hours for 7 days
fludrocortisoneDrug
50 µg once a day via a nasogastric tube for seven days
HydrocortisoneDrug
hydrocortisone 50mg q6 for 7 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Hydrocortisone and convention glycemic control Receives: Drug: hydrocortisone |
| 2 | Experimental | Hydrocortisone and fludrocortisone and conventional glucose control Receives: Drug: hydrocortisone; Drug: fludrocortisone |
| 3 | Experimental | Hydrocortisone and intensive insulin therapy Receives: Drug: recombinant human insulin; Drug: hydrocortisone |
| 4 | Experimental | hydrocortisone, fludrocortisone and intensive insulin therapy Receives: Drug: recombinant human insulin; Drug: hydrocortisone; Drug: fludrocortisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
In-hospital mortality
Measured: Day 180
Secondary outcomes (8)
Secondary outcomes :
Measured: Day 180
90-day and 180-day mortality.
Measured: Day 180
Duration of life-supporting treatments (i.e. vasopressors and mechanical ventilation)
Measured: Day 180
Time to resolve multiple organ dysfunction, i.e. to obtain a SOFA score < 8
Measured: Day 180
Hospital length of stay.
Measured: Day 180
Number of hypoglycaemic events (blood glucose < 4 mmol/l) during insulin infusion
Measured: Day 180
Muscle weakness at discharge from intensive care unit, 90-day and 180-day
Measured: Day 180
Post traumatic stress disorders
Measured: Day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2006 (estimated)
- Study startJan 2006
- Primary completionJan 2009
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 508 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Versailles
- Sponsor type
- University, hospital or other
- Collaborators
- Assistance Publique - Hôpitaux de Paris
- Investigators
- Djillali annane, MD, PhD, Study chair, Assistance Publique Hôpitaux de Paris - University of Versailles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00320099
- Sponsor's protocol ID
- AOM04100
- Other IDs
- P040421
- Acronym
- COIITSS
- Status last verified
- Apr 2010
- First submitted
- 27 Apr 2006
- Last updated
- 6 Apr 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
COIITSS Study Investigators; Annane D, Cariou A, Maxime V, Azoulay E, D'honneur G, Timsit JF, Cohen Y, Wolf M, Fartoukh M, Adrie C, Santre C, Bollaert PE, Mathonet A, Amathieu R, Tabah A, Clec'h C, Mayaux J, Lejeune J, Chevret S. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA. 2010 Jan 27;303(4):341-8. doi: 10.1001/jama.2010.2.
PubMed 20103758
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Study of Corticotherapy (Hydrocortisone Alone Versus Hydrocortisone Plus Fludrocortisone) Versus Corticotherapy Plus Intensive Insulin Therapy for Septic Shock
- ClinicalTrials.gov ID
- NCT00320099
- Acronym / sponsor ID
- COIITSS / AOM04100
- Conditions
- Septic Shock
- Keywords
- septic shock, adrenal insufficiency, glucose control, mineralocorticoids
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 508 participants (actual)
- Lead sponsor
- University of VersaillesUniversity, hospital or other
- Collaborators
- Assistance Publique - Hôpitaux de Paris
- Study start
- Jan 2006
- Primary completion
- Jan 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 3 May 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.
This study will compare, in adults with septic shock, the safety and efficacy of a combination of moderate doses of corticosteroids and intensive insulin therapy to that of moderate doses of corticosteroids. In addition, this study will compare the efficacy and safety of hydrocortisone alone versus hydrocortisone plus fludrocortisone
Detailed description
Objectives:
Comparison, in patients with septic shock, of efficacy and safety of the combination of moderate doses of corticosteroids and intensive insulin therapy to that of moderate doses of corticosteroids; and of efficacy and safety of hydrocortisone alone versus hydrocortisone plus fludrocortisone Methods
Study design :
This is a multicenter, prospective, randomised trial on parallel groups
Study treatments :
Experimental arm A:
A1=50 mg iv every 6 hours of hydrocortisone (hemisuccinate), 50µg through the nasogastric tube of 9 alpha fludrocortisone, for 7 days AND strict control of blood glucose levels with a target of 4,4 to 6 mmol/L using continuous iv infusion of insulin up to intensive care unit discharge.
A2=50 mg iv every 6 hours of hydrocortisone (hemisuccinate) for 7 days AND strict control of blood glucose levels with a target of 4,4 to 6 mmol/L using continuous iv infusion of insulin up to intensive care unit discharge.
Control arm B:
B1:50 mg iv every 6 hours of hydrocortisone (hemisuccinate), 50µg through the nasogastric tube of 9 alpha fludrocortisone, for 7 days.
B2:50 mg iv every 6 hours of hydrocortisone (hemisuccinate)for 7 days. Study Primary outcome : In-hospital mortality
Sample size calculation :
The expected in-hospital mortality rate in the control group is 50%. To detect an absolute reduction in in-hospital mortality rate of 12.5 %, that is 37.5% in the experimental arm versus 50% in the control arm, and considering risk alpha of 0,05 and a risk beta of 0,20, 254 patients per treatment arms are needed, for a total of 508 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: hydrocortisoneHydrocortisone and convention glycemic control |
| 2 | Experimental | Drug: hydrocortisone, Drug: fludrocortisoneHydrocortisone and fludrocortisone and conventional glucose control |
| 3 | Experimental | Drug: recombinant human insulin, Drug: hydrocortisoneHydrocortisone and intensive insulin therapy |
| 4 | Experimental | Drug: recombinant human insulin, Drug: hydrocortisone, Drug: fludrocortisonehydrocortisone, fludrocortisone and intensive insulin therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients admitted in intensive care units for septic shock and meeting all following criteria
- Proven infection
- Need for vasopressor to maintain systemic arterial tension above 90 mmHg
- Multiple organ dysfunction as defined by a SOFA score ³ 8.
- Need for treatment with moderate dose of corticosteroids
Key exclusion criteria (4 listed)
- Pregnancy
- Less than 18 years old
- Moribund (i.e. expected to die on day of intensive care unit admission)
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 |
|---|---|---|
| recombinant human insulinintensive insulin therapy as a continuous infusion to maintain blood glucose levels between 4 and 6 mmol/l | Drug | 3, 4 |
| hydrocortisone50 mg as iv bolus every 6 hours for 7 days | Drug | 1, 2, 3, 4 |
| fludrocortisone50 µg once a day via a nasogastric tube for seven days | Drug | 2, 4 |
| Hydrocortisonehydrocortisone 50mg q6 for 7 days | Drug | 1 |
Primary outcome
In-hospital mortality
Time frame: Day 180
8 secondary outcomes
Secondary outcomes :
Time frame: Day 180
90-day and 180-day mortality.
Time frame: Day 180
Duration of life-supporting treatments (i.e. vasopressors and mechanical ventilation)
Time frame: Day 180
Time to resolve multiple organ dysfunction, i.e. to obtain a SOFA score < 8
Time frame: Day 180
Hospital length of stay.
Time frame: Day 180
Number of hypoglycaemic events (blood glucose < 4 mmol/l) during insulin infusion
Time frame: Day 180
Muscle weakness at discharge from intensive care unit, 90-day and 180-day
Time frame: Day 180
Post traumatic stress disorders
Time frame: Day 180
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2010.
- Results publication: PubMed 20103758COIITSS Study Investigators; Annane D, Cariou A, Maxime V, Azoulay E, D'honneur G, Timsit JF, Cohen Y, Wolf M, Fartoukh M, Adrie C, Santre C, Bollaert PE, Mathonet A, Amathieu R, Tabah A, Clec'h C, Mayaux J, Lejeune J, Chevret S. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA. 2010 Jan 27;303(4):341-8. doi: 10.1001/jama.2010.2.
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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.
Djillali annane, MD, PhD study chair
Assistance Publique Hôpitaux de Paris - University of Versailles
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing recombinant human insulin, hydrocortisone and fludrocortisone in people with Septic Shock, run by University of Versailles at 8 sites in France.
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 5 inclusion and 4 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: finished, as of the sponsor's last update on 6 Apr 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
In-hospital mortality (time frame: Day 180). 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 NCT00320099, which also lists 1 linked publication.
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 6 Apr 2010.