Septic ShockPhase 2/3CATSNCT00148278
Norepinephrine Plus Dobutamine Versus Epinephrine Alone for the Management of Septic Shock
A Phase 2/3 study testing norepinephrine and dobutamine in people with Septic Shock and Severe Sepsis, run by University of Versailles at 15 sites in France.
Trial summary
Catecholamines infusion is a major component of septic shock management. International guidelines recommend that norepinephrine should be preferred to epinephrine, though phase III trials are lacking. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Severe Sepsis, Infections
- What is being tested?
- norepinephrine and dobutamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 330 participants
- Where
- 15 sitesFrance
- Study dates
- Oct 1999to Dec 2005
- Phase
- Phase 2/3
- 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
- Adults over 18 years
- Informed consent
- Presenting from less than 7 days :
- One or more infectious site
- At least 2 of the following criteria: temperature > 38°C or < 36.5°C, respiratory rate > 20 breaths per min or PaCO2 < 32 mmHg or mechanical ventilation, heart rate > 90 beats/min, white blood cell count > 12,000/mm3 or < 4,000/mm3
- At least 2 of the following criteria: PaO2/FiO2 ratio <280 mmHg (if mechanical ventilation, urinary output of less than 0.5 mL/kg of body weight or < 30 mL/h at least 1 hour, plasma lactate > 2 mmol/L, platelet count < 100,000 /mm3
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- And presenting from at least 24 hours:
- Systolic blood pressure < 90 mmHg or mean blood pressure < 70 mmHg (for at least 30 min);
- 1000 mL fluid replacement or pulmonary capillary wedge pressure > 12 mmHg
- Dopamine infusion at 15 µg/kg/min for at least 1 hour, or epinephrine or norepinephrine in first intention
Who cannot join
- Pregnant woman
- Obstructive cardiomyopathy
- Acute coronary disease
- Non infectious shock
- Care limitation
- White blood cell count < 500 /mm3
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
France15 sites
Réanimation Médicale - Hôpital Louis Mourier
Colombes, 92700
Réanimation Polyvalente - Hôpital de Corbeil
Corbeil, 91100
Service de Réanimation Médicale - Hôpital Poincaré
Garches, 92380
Réanimation Médicale - Hôpital André Mignot
Le Chesnay, 78157
Réanimation Polyvalente - Hôpital Dupuytren
Limoges, 87000
Réanimation Polyvalente - Hôpital Nord
Marseille, 13009
Réanimation Chirurgicale - Hôpital Central
Nancy, 54035
Service de Réanimation Médicale - Hôpital Central
Nancy, 54035
Service d'anesthésiologie - HIA Val de Grâce
Paris, 75005
Réanimation Médicale - Hôpital Saint Louis
Paris, 75010
Réanimation Polyvalente - Hôpital Saint Joseph
Paris, 75014
Réanimation Médicale - Hôpital Georges Pompidou
Paris, 75908
Réanimation Médicale - CHI de Poissy
Poissy, 78303
Réanimation - CH Victor Provo
Roubaix, 59100
Réanimation Polyvalente - Institut Gustave Roussy
Villejuif, 94800
About this study
Official title: Prospective, Multicenter, Randomized, Double-Blind Study Comparing Safety and Efficacy of Norepinephrine Plus Dobutamine Versus Epinephrine Alone in Septic Shock.
Catecholamines infusion is a major component of septic shock management. International guidelines recommend that norepinephrine should be preferred to epinephrine, though phase III trials are lacking. The present study aimed at comparing the efficacy and safety of norepinephrine plus dobutamine to that of epinephrine in adults with septic shock.
Read the detailed description
The french Conference on Consensus on catecholamines use in septic shock has underlined the importance of carrying out a clinical trial to clarify the use of epinephrine, norepinephrine and dobutamine in the management of multiple organ failure associated with severe sepsis. The main objective of the study was therefore to compare the effects of the combination of dobutamine and norepinephrine to those of epinephrine alone in patients with septic shock. In this purpose, patients were randomly assigned to receive either epinephrine or norepinephrine plus dobutamine and drugs were titrated to maintain blood pressure over 70 mmHg. Main outcome was 28-day mortality.
- Conditions
- Septic Shock, Severe Sepsis, Infections
- Being tested
- norepinephrine and dobutamine, epinephrine plus placebo of dobutamine
- Keywords
- Catecholamines, Septic shock
- Medical subject headings
- Shock, Septic, Sepsis, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
norepinephrine and dobutamineDrug
continuous infusion of norepinephrine titrated to maintain a mean arterial pressure at 70mmHg or more and dobutamine could be added as a continuous infusion when cardiac index was of less than 2.5 liters per squared meter of body surface
epinephrine plus placebo of dobutamineDrug
epinephrine was titrated to maintain a mean arterial pressure at 70mmHg or more and placebo of dobutamine was titrated in case of a cardiac index lower than 2.5 liters per squared meters of body surface
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | norepinephrine plus dobutamine Receives: Drug: norepinephrine and dobutamine |
| 2 | Active comparator | epinephrine Receives: Drug: epinephrine plus placebo of dobutamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
28 Day mortality
Measured: 28 Day
Secondary outcomes (10)
-28-day survival distribution
Measured: Day 28
-Survival rate at days 14, 28, 90, 6 months and 1 year.
Measured: one year
-Rate of patients with secondary care limitation
Measured: one year
-Organ failure between randomization and day 28.
Measured: Day 28
-Serious adverse events between randomization and exit of intensive care unit.
Measured: one year
-Onset of a reversible clinical event between randomization and exit of intensive care unit (bronchospasm, cutaneous rash, tachycardia)
Measured: one year
-Time on vasopressors
Measured: Day 90
-Time in intensive care unit
Measured: one year
-Time in hospital
Measured: one year
-Costs
Measured: Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2005 (estimated)
- Study startOct 1999
- Primary completionDec 2004
- Study completionDec 2005
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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 330 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 director, Assistance Publique Hôpitaux de Paris - University of VersaillesEric Bellissant, MD, PhD, Study chair, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00148278
- Sponsor's protocol ID
- AFSSAPS 990931
- Other IDs
- AOM97123, CIC0203/001
- Acronym
- CATS
- Status last verified
- Jul 2010
- First submitted
- 1 Sep 2005
- Last updated
- 22 Jul 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troche G, Ricard JD, Nitenberg G, Papazian L, Azoulay E, Bellissant E; CATS Study Group. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet. 2007 Aug 25;370(9588):676-84. doi: 10.1016/S0140-6736(07)61344-0.
PubMed 17720019
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Multicenter, Randomized, Double-Blind Study Comparing Safety and Efficacy of Norepinephrine Plus Dobutamine Versus Epinephrine Alone in Septic Shock.
- ClinicalTrials.gov ID
- NCT00148278
- Acronym / sponsor ID
- CATS / AFSSAPS 990931
- Conditions
- Septic Shock, Severe Sepsis, Infections
- Keywords
- Catecholamines, Septic shock
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 330 participants (actual)
- Lead sponsor
- University of VersaillesUniversity, hospital or other
- Collaborators
- Assistance Publique - Hôpitaux de Paris
- Study start
- Oct 1999
- Primary completion
- Dec 2004 (actual)
- Study completion
- Dec 2005 (actual)
- First posted
- 7 Sep 2005 (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.
Catecholamines infusion is a major component of septic shock management. International guidelines recommend that norepinephrine should be preferred to epinephrine, though phase III trials are lacking. The present study aimed at comparing the efficacy and safety of norepinephrine plus dobutamine to that of epinephrine in adults with septic shock.
Detailed description
The french Conference on Consensus on catecholamines use in septic shock has underlined the importance of carrying out a clinical trial to clarify the use of epinephrine, norepinephrine and dobutamine in the management of multiple organ failure associated with severe sepsis. The main objective of the study was therefore to compare the effects of the combination of dobutamine and norepinephrine to those of epinephrine alone in patients with septic shock. In this purpose, patients were randomly assigned to receive either epinephrine or norepinephrine plus dobutamine and drugs were titrated to maintain blood pressure over 70 mmHg. Main outcome was 28-day mortality.
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 |
|---|---|---|
| 1 | Experimental | Drug: norepinephrine and dobutaminenorepinephrine plus dobutamine |
| 2 | Active comparator | Drug: epinephrine plus placebo of dobutamineepinephrine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adults over 18 years
- Informed consent
- One or more infectious site
- At least 2 of the following criteria: temperature > 38°C or < 36.5°C, respiratory rate > 20 breaths per min or PaCO2 < 32 mmHg or mechanical ventilation, heart rate > 90 beats/min, white blood cell count > 12,000/mm3 or < 4,000/mm3
- At least 2 of the following criteria: PaO2/FiO2 ratio <280 mmHg (if mechanical ventilation, urinary output of less than 0.5 mL/kg of body weight or < 30 mL/h at least 1 hour, plasma lactate > 2 mmol/L, platelet count < 100,000 /mm3
Key exclusion criteria (6 listed)
- Pregnant woman
- Obstructive cardiomyopathy
- Acute coronary disease
- Non infectious shock
- Care limitation
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 |
|---|---|---|
| norepinephrine and dobutaminecontinuous infusion of norepinephrine titrated to maintain a mean arterial pressure at 70mmHg or more and dobutamine could be added as a continuous infusion when cardiac index was of less than 2.5 liters per squared meter of body surface | Drug | 1 |
| epinephrine plus placebo of dobutamineepinephrine was titrated to maintain a mean arterial pressure at 70mmHg or more and placebo of dobutamine was titrated in case of a cardiac index lower than 2.5 liters per squared meters of body surface | Drug | 2 |
Primary outcome
28 Day mortality
Time frame: 28 Day
10 secondary outcomes
-28-day survival distribution
Time frame: Day 28
-Survival rate at days 14, 28, 90, 6 months and 1 year.
Time frame: one year
-Rate of patients with secondary care limitation
Time frame: one year
-Organ failure between randomization and day 28.
Time frame: Day 28
-Serious adverse events between randomization and exit of intensive care unit.
Time frame: one year
-Onset of a reversible clinical event between randomization and exit of intensive care unit (bronchospasm, cutaneous rash, tachycardia)
Time frame: one year
-Time on vasopressors
Time frame: Day 90
-Time in intensive care unit
Time frame: one year
-Time in hospital
Time frame: one year
-Costs
Time frame: Day 90
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 22 Jul 2010.
- Results publication: PubMed 17720019Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troche G, Ricard JD, Nitenberg G, Papazian L, Azoulay E, Bellissant E; CATS Study Group. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet. 2007 Aug 25;370(9588):676-84. doi: 10.1016/S0140-6736(07)61344-0.
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Sepsis
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 director
Assistance Publique Hôpitaux de Paris - University of Versailles
Eric Bellissant, MD, PhD study chair
Rennes University Hospital
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing norepinephrine and dobutamine in people with Septic Shock and Severe Sepsis, run by University of Versailles at 15 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 10 inclusion and 6 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 22 Jul 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
28 Day mortality (time frame: 28 Day). 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 NCT00148278, 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 22 Jul 2010.