Invasive CandidiasisPhase 3EMPIRICUSNCT01773876
Empirical Antifungal Treatment in ICUS
A Phase 3 study testing Micafungin in people with Invasive Candidiasis, run by University Hospital, Grenoble at 22 sites in France.
Trial summary
Invasive Candida infections are burdened with a high mortality rate and is very common in intensive care units. This study aims to evaluate the efficacy of empirical treatment with micafungin in adult patients with suspected invasive candidiasis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Invasive Candidiasis
- What is being tested?
- Micafungin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 260 participants
- Where
- 22 sitesFrance
- Study dates
- Jul 2012to Feb 2015
- 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
- Age ≥ 18 years
- Persistent sepsis without documented invasive candidiasis:
- systemic inflammatory response syndrome (SIRS) presence of two signs on the 4 [temperature <36 ° C or> 38 ° C, heart rate> 90/min, respiratory rate> 20/min or PaCO2 <32 mmHg, leukocytosis> 12,000 / mm3, <4.000/mm3 or presence of circulating immature forms (> 10% of cells)] mechanical ventilation (intubation or tracheostomy) for over 4 days (96 hours) central line use of broad-spectrum antibacterial for more than 4 calendar days (96 hours) in the previous week presence of at least one extra-digestive site colonized by Candida sp. (Urine, mouth, throat, upper and lower respiratory tract, skin folds, and suction drains after surgery ...), not lower digestive tract, are not taken into account the positive samples of rectal swabs and / or stool cultures, absence of proven bacterial infections untreated no evidence of invasive fungal infections (positive blood culture, positive culture of a surgical site, deep biopsy with fungal) infection or mold according to the criteria of the group "fungal infection of the EORTC" organ failure
- Hospitalization in intensive care for over 5 days (120 hours)
- Giving a free, informed and in writing. In the absence of the person of trust or a family member (if present)consent to emergency possible.
- Receiving a social security system,
- Negative pregnancy test for patients of childbearing age
Who cannot join
- Proven invasive fungal infection (positive blood culture, positive culture of a surgical site, deep biopsy with fungal infection), including aspergillosis requiring antifungal therapy at the time of randomization
- Prognosis of less than 48 hours (for which the patient outcome will be fatal whatever treatment),
- Echinocandin antifungal treatment by more than one day or another antifungal for over 72 hours in the week before the inclusion visit,
- Allergy, hypersensitivity or known intolerance to echinocandins antifungal or any of the excipients of the drug
- Neutropenia (ANC <500/mm3)
- History of organ and bone marrow,
Show all 13Show fewer
- Recent chemotherapy (less than 6 months)
- Systemic immunosuppressive therapy in progress, other than with corticosteroids at doses below 2 mg / kg / day of prednisolone or equivalent
- Participation in another interventional study in the same ICU stay or making treatment being evaluated within 28 days prior to randomization
- Any clinical investigator deems incompatible with the conduct of the study in acceptable security conditions
- Pregnant and lactating women,
- Adults subject to a legal protection measure
- Persons deprived of their liberty by a judicial or administrative decision, those hospitalized without consent, persons admitted to a health facility or social purposes other than research
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
France22 sites
Hospital Aix en Provence
Aix-en-Provence, 13616
Hospital University of Besançon
Besançon, 67091
University Hospital of Avicennes
Bobigny, 93009
Hospital University of Bordeaux
Bordeaux, 33000
Hospital University of Clermont Ferrand
Clermont-Ferrand, 63003
University Hospital of Beaujon
Clichy, 92110
University Hospital of Dijon
Dijon, 21000
Hospital of Draguignan
Draguignan, 83300
Hospital University of Grenoble
Grenoble, 38043
Departemental Hospital of Roche sur Yon
La Roche-sur-Yon, 85925
Hospital of Versailles
Le Chesnay, 78150
University Hospital Edouard Herriot
Lyon, 96433
Hospital University of Montpellier
Montpellier, 34295
Interegional Hospital André Grégoire
Montreuil, 93105
University Hospital Saint Louis
Paris, 75010
University Hospital of La Pitié Salpetrière
Paris, 75013
Hospital St Joseph
Paris, 75014
Hospital University of Bichat
Paris, 75877
Hospital of Pontoise
Pontoise, 95303
Hospital University of Reims
Reims, 51092
University Hospital of Saint Etienne
Saint-Etienne, 42055
University Hospital of Strasbourg
Strasbourg, 67091
About this study
Official title: Micafungin Versus Placebo in the Nosocomial Sepsis in Patients Multi-colonized With Candida, Randomized Controlled Trial
Invasive Candida infections are burdened with a high mortality rate and is very common in intensive care units. This study aims to evaluate the efficacy of empirical treatment with micafungin in adult patients with suspected invasive candidiasis.
Read the detailed description
Multicenter, randomized, double-blind parallel groups comparing adult patients with suspected invasive candidiasis input from a 14-day empirical treatment with micafungin (MYCAMINE 100 mg) with placebo on survival without invasive candidiasis in 28 days after initiation of study treatment.
- Conditions
- Invasive Candidiasis
- Being tested
- Micafungin, PLACEBO
- Keywords
- survival without proven invasive candidiasis, effectiveness, micafungin versus placebo, pharmacokinetic, pharmacodynamic, tolerance
- Medical subject headings
- Candidiasis, Invasive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MicafunginDrug
MYCAMINE 100 mg intravenous 100 mg of powder reconstituted in a 100 ml infusion bag of sodium chloride 0.9%
infusion over 24 hours for 14 days discontinuation of treatment if proven invasive candidiasis
PLACEBODrug
solution of sodium chloride 0.9% 100 ml for intravenous infusion infusion over 24 hours for 14 days discontinuation of placebo if proven invasive candidiasis
| Study group | Role | What they receive |
|---|---|---|
| Micafungin | Active comparator | MYCAMINE 100 mg intravenous an injection of 24 hours Receives: Drug: Micafungin |
| PLACEBO | Placebo comparator | 0.9% sodium chlorides 100ml infusion Receives: Drug: PLACEBO |
What is being measured
The primary outcome is the main question the study is designed to answer.
survival to 28 days without proven fungal infection (a fungal infection occurring within 48 hours after inclusion will be considered available for inclusion)
breakthrough infection defined as a proven infection occurs at least 48 hours after initiation of treatment Proven infection is considered purchased after enrollment if the first significant positive levy occurs after the 48 th hour after enrollment.
Measured: 28 days follow-up
Secondary outcomes (11)
pharmacokinetic parameters: estimated gross exposure indices: AUC, Cmax, Cmin
Reports AUC / MIC and Cmax / MIC will be calculated
Measured: during 24 hours (between the two first infusions)
evaluation of tolerance
For all patients who received at least one dose of treatment:
- number of adverse events reported after randomization up to 28 days, only death will count up to 3 months post-randomization (information on the long-term survival collected by telephone),
- changes in the clinical examination, vital signs and laboratory results,
- overall survival defined as the time from randomization to date of death from any cause.
- Changes in liver function tests (bilirubin, ALT, AST, rate prothrombin, alkaline phosphatase) at the end of treatment and at the end study
Measured: 3 months
pharmacodynamic parameters: potential serum biomarkers of treatment efficacy (PCR Candida,1,3 β-D-glucan,mannan antigenemia,anti-mannan,Procalcitonin (proCT))
Measured: during 28 days
pharmacodynamic parameters: Early prognostic factors of response: J7 survival without proven invasive candidiasis
Measured: during 14 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible on all-cause mortality at day 28 (end of study) and J90 (3 months post-randomization)
Measured: during 90 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis can free survival antifungal treatment at day 28
Measured: during 28 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of organ failure during the study
Measured: during 90 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible the use of mechanical ventilation during the study
Measured: during 90 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of the colonization index during study
Measured: during 90 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible changes in serum biomarkers (1-3 β-D-glucan, mannan antigenemia, anti-mannan Candida PCR) during the study
Measured: during 90 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible on the incidence of pneumonia acquired bacterial mechanical ventilation (VAP).
Measured: during 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2013 (estimated)
- Study startJul 2012
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Invasive CandidiasisStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 260 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- TIMSIT JFT Jean François, PU-PH, Principal investigator, University Hospital, Grenoble
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01773876
- Sponsor's protocol ID
- 1126
- Other IDs
- 2011-005451-14
- Acronym
- EMPIRICUS
- Status last verified
- Mar 2015
- First submitted
- 14 Jan 2013
- Last updated
- 24 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Timsit JF, Azoulay E, Schwebel C, Charles PE, Cornet M, Souweine B, Klouche K, Jaber S, Trouillet JL, Bruneel F, Argaud L, Cousson J, Meziani F, Gruson D, Paris A, Darmon M, Garrouste-Orgeas M, Navellou JC, Foucrier A, Allaouchiche B, Das V, Gangneux JP, Ruckly S, Maubon D, Jullien V, Wolff M; EMPIRICUS Trial Group. Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure: The EMPIRICUS Randomized Clinical Trial. JAMA. 2016 Oct 18;316(15):1555-1564. doi: 10.1001/jama.2016.14655.
PubMed 27706483Timsit JF, Azoulay E, Cornet M, Gangneux JP, Jullien V, Vesin A, Schir E, Wolff M. EMPIRICUS micafungin versus placebo during nosocomial sepsis in Candida multi-colonized ICU patients with multiple organ failures: study protocol for a randomized controlled trial. Trials. 2013 Nov 21;14:399. doi: 10.1186/1745-6215-14-399.
PubMed 24261608
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Micafungin Versus Placebo in the Nosocomial Sepsis in Patients Multi-colonized With Candida, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01773876
- Acronym / sponsor ID
- EMPIRICUS / 1126
- Conditions
- Invasive Candidiasis
- Keywords
- survival without proven invasive candidiasis, effectiveness, micafungin versus placebo, pharmacokinetic, pharmacodynamic, tolerance
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 260 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 23 Jan 2013 (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.
Invasive Candida infections are burdened with a high mortality rate and is very common in intensive care units. This study aims to evaluate the efficacy of empirical treatment with micafungin in adult patients with suspected invasive candidiasis.
Detailed description
Multicenter, randomized, double-blind parallel groups comparing adult patients with suspected invasive candidiasis input from a 14-day empirical treatment with micafungin (MYCAMINE 100 mg) with placebo on survival without invasive candidiasis in 28 days after initiation of study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Micafungin | Active comparator | Drug: MicafunginMYCAMINE 100 mg intravenous an injection of 24 hours |
| PLACEBO | Placebo comparator | Drug: PLACEBO0.9% sodium chlorides 100ml infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 18 years
- Persistent sepsis without documented invasive candidiasis:
- systemic inflammatory response syndrome (SIRS) presence of two signs on the 4 [temperature <36 ° C or> 38 ° C, heart rate> 90/min, respiratory rate> 20/min or PaCO2 <32 mmHg, leukocytosis> 12,000 / mm3, <4.000/mm3 or presence of circulating immature forms (> 10% of cells)] mechanical ventilation (intubation or tracheostomy) for over 4 days (96 hours) central line use of broad-spectrum antibacterial for more than 4 calendar days (96 hours) in the previous week presence of at least one extra-digestive site colonized by Candida sp. (Urine, mouth, throat, upper and lower respiratory tract, skin folds, and suction drains after surgery ...), not lower digestive tract, are not taken into account the positive samples of rectal swabs and / or stool cultures, absence of proven bacterial infections untreated no evidence of invasive fungal infections (positive blood culture, positive culture of a surgical site, deep biopsy with fungal) infection or mold according to the criteria of the group "fungal infection of the EORTC" organ failure
- Hospitalization in intensive care for over 5 days (120 hours)
- Giving a free, informed and in writing. In the absence of the person of trust or a family member (if present)consent to emergency possible.
Key exclusion criteria (13 listed)
- Proven invasive fungal infection (positive blood culture, positive culture of a surgical site, deep biopsy with fungal infection), including aspergillosis requiring antifungal therapy at the time of randomization
- Prognosis of less than 48 hours (for which the patient outcome will be fatal whatever treatment),
- Echinocandin antifungal treatment by more than one day or another antifungal for over 72 hours in the week before the inclusion visit,
- Allergy, hypersensitivity or known intolerance to echinocandins antifungal or any of the excipients of the drug
- Neutropenia (ANC <500/mm3)
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 |
|---|---|---|
| MicafunginMYCAMINE 100 mg intravenous 100 mg of powder reconstituted in a 100 ml infusion bag of sodium chloride 0.9% infusion over 24 hours for 14 days discontinuation of treatment if proven invasive candidiasis | Drug | Micafungin |
| PLACEBOsolution of sodium chloride 0.9% 100 ml for intravenous infusion infusion over 24 hours for 14 days discontinuation of placebo if proven invasive candidiasis | Drug | PLACEBO |
Primary outcome
survival to 28 days without proven fungal infection (a fungal infection occurring within 48 hours after inclusion will be considered available for inclusion)
Time frame: 28 days follow-up
breakthrough infection defined as a proven infection occurs at least 48 hours after initiation of treatment Proven infection is considered purchased after enrollment if the first significant positive levy occurs after the 48 th hour after enrollment.
11 secondary outcomes
pharmacokinetic parameters: estimated gross exposure indices: AUC, Cmax, Cmin
Time frame: during 24 hours (between the two first infusions)
evaluation of tolerance
Time frame: 3 months
pharmacodynamic parameters: potential serum biomarkers of treatment efficacy (PCR Candida,1,3 β-D-glucan,mannan antigenemia,anti-mannan,Procalcitonin (proCT))
Time frame: during 28 days
pharmacodynamic parameters: Early prognostic factors of response: J7 survival without proven invasive candidiasis
Time frame: during 14 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible on all-cause mortality at day 28 (end of study) and J90 (3 months post-randomization)
Time frame: during 90 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis can free survival antifungal treatment at day 28
Time frame: during 28 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of organ failure during the study
Time frame: during 90 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible the use of mechanical ventilation during the study
Time frame: during 90 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of the colonization index during study
Time frame: during 90 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible changes in serum biomarkers (1-3 β-D-glucan, mannan antigenemia, anti-mannan Candida PCR) during the study
Time frame: during 90 days
Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible on the incidence of pneumonia acquired bacterial mechanical ventilation (VAP).
Time frame: during 90 days
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 24 Mar 2015.
- Derived from this study: PubMed 27706483Timsit JF, Azoulay E, Schwebel C, Charles PE, Cornet M, Souweine B, Klouche K, Jaber S, Trouillet JL, Bruneel F, Argaud L, Cousson J, Meziani F, Gruson D, Paris A, Darmon M, Garrouste-Orgeas M, Navellou JC, Foucrier A, Allaouchiche B, Das V, Gangneux JP, Ruckly S, Maubon D, Jullien V, Wolff M; EMPIRICUS Trial Group. Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure: The EMPIRICUS Randomized Clinical Trial. JAMA. 2016 Oct 18;316(15):1555-1564. doi: 10.1001/jama.2016.14655.
- Derived from this study: PubMed 24261608Timsit JF, Azoulay E, Cornet M, Gangneux JP, Jullien V, Vesin A, Schir E, Wolff M. EMPIRICUS micafungin versus placebo during nosocomial sepsis in Candida multi-colonized ICU patients with multiple organ failures: study protocol for a randomized controlled trial. Trials. 2013 Nov 21;14:399. doi: 10.1186/1745-6215-14-399.
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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.
TIMSIT JFT Jean François, PU-PH principal investigator
University Hospital, Grenoble
22 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 Micafungin in people with Invasive Candidiasis, run by University Hospital, Grenoble at 22 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 7 inclusion and 13 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 24 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 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. Some participants in this study may receive a placebo. 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?
survival to 28 days without proven fungal infection (a fungal infection occurring within 48 hours after inclusion will be considered available for inclusion) (time frame: 28 days follow-up). 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 NCT01773876, which also lists 2 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 24 Mar 2015.