Clinical trial NCT01122368: A Study to Evaluate Pre-emptive Treatment for Invasive Candidiasis in High Risk Surgical Subjects
Official title: An Exploratory Study to Compare the Efficacy and Safety of Micafungin as a Pre-emptive Treatment of Invasive Candidiasis Versus Placebo in High Risk Surgical Subjects - A Multicentre, Randomized, Double-blind Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mycoses
Keywords: mycoses
Micafungin
intra-abdominal surgery
invasive fungal infection
intra-abdominal infection
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2010-05-13
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Subjects with intra-abdominal infection requiring surgery and Intensive Care Unit stay will be treated early with micafungin or placebo to determine the incidence and time to confirmation of fungal infection.

Detailed description: Subjects will be assessed at the following visits:

* Baseline (after surgery, prior to randomization)
* End of Treatment (EOT) visit (EOT is defined as: requires alternative antifungal, sufficient improvement of surgical condition, confirmed fungal infection or death)
* End of Study visit (28 days after the EOT visit)
* Long-term Follow up visit (90 days after the EOT visit)

Eligibility criteria: Inclusion Criteria:

* Intra-abdominal infection requiring surgery and Intensive Care Unit stay
* If Community Acquired Intra-Abdominal Infection, at least 72 hours (but not more than 120 hours) of Intensive Care Unit stay, counted from the end of surgery, and a further expected duration of Intensive Care Unit stay of ≥ 48 hours
* If Nosocomial Intra-Abdominal Infection, duration of Intensive Care Unit stay ≤ 48 hours, counted from the end of surgery, and a further expected duration of Intensive Care Unit stay of ≥ 48 hours
* Female subject of childbearing potential must have a negative urine or serum pregnancy test prior to randomization and must agree to maintain highly effective birth control during the study

Exclusion Criteria:

* Acute pancreatitis
* Neutropenia (ANC \<1,000/mm3) at the time of randomization
* Infected intra-peritoneal dialysis
* Patients undergoing solid organ transplantation
* Documented invasive candidiasis at the time of randomization
* Expected survival \< 48 hours
* Any systemically active anti-fungal within 14 days prior to administration of the study drug
* Allergy, hypersensitivity, or any serious reaction to an echinocandin anti-fungal or any of the study drug excipients
* Currently receiving and/or has taken an investigational drug within 28 days prior to randomization
* Pregnant woman or breast-feeding mother
* 'Do Not Resuscitate' order

Primary outcomes:
measure: The incidence of Invasive Fungal Infection
timeFrame: During treatment
measure: Time from baseline to the first confirmation of Invasive Fungal Infection
timeFrame: Baseline to End of Treatment visit
Secondary outcomes:
measure: The incidence during the treatment period and the time to confirmation of the composite endpoint (defined as confirmation of Invasive Fungal Infection and/or administration of alternative anti-fungal therapy)
timeFrame: At the EOT visit
measure: The emergence or persistence of fungal colonization
timeFrame: At the EOT visit
measure: The level of organ dysfunction
timeFrame: At the EOT visit
measure: To assess the requirement for additional abdominal surgery/intervention.
timeFrame: At the End of Study visit
measure: Organ failure-free days
timeFrame: From Day 1 until 28 days after end of study drug treatment
measure: Fungal-free survival
timeFrame: From Day 1 until 28 days after end of study drug treatment
measure: Intensive Care Unit (ICU)-free days
timeFrame: From Day 1 until 28 days after end of study drug treatment
measure: All-cause mortality
timeFrame: At the End of Study and Long-Term Follow Up visit
measure: Health-related quality of life
timeFrame: At the End of Study visit
measure: Assessment of the safety of micafungin when used as a pre-emptive treatment
timeFrame: At the End of Study visit
Other outcomes:
Locations:
city: Innsbruck
country: Austria
city: Salzburg
country: Austria
city: Wien
country: Austria
city: Wien
country: Austria
city: Brussels
country: Belgium
city: Brussels
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Liege
country: Belgium
city: Viborg
country: Denmark
city: Jyvaskyla
country: Finland
city: Kuopio
country: Finland
city: Tampere
country: Finland
city: Amiens
country: France
city: La Roche sur Yon Cedex 9
country: France
city: Limoges
country: France
city: Paris Cedex 14
country: France
city: Paris
country: France
city: Pierre Benite
country: France
city: Poitiers
country: France
city: Freiburg
country: Germany
city: Hannover
country: Germany
city: Koln
country: Germany
city: Leipzig
country: Germany
city: Lubeck
country: Germany
city: Athens
country: Greece
city: Thessaloniki
country: Greece
city: Thessaloniki
country: Greece
city: Debrecen
country: Hungary
city: Gyor
country: Hungary
city: Szeged
country: Hungary
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
city: Bologna
country: Italy
city: Milano
country: Italy
city: Monza
country: Italy
city: Pisa
country: Italy
city: Roma
country: Italy
city: Roma
country: Italy
city: Verona
country: Italy
city: Bucharest
country: Romania
city: Oradea
country: Romania
city: Timisoara
country: Romania
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Valladolid
country: Spain
city: Lausanne
country: Switzerland
city: Ankara
country: Turkey
city: Ege
country: Turkey
city: Eskisehir
country: Turkey
city: Trabzon
country: Turkey
city: Blackpool
country: United Kingdom
city: Leeds
country: United Kingdom
city: Leeds
country: United Kingdom
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Use Central Contact
role: STUDY_CHAIR
References:
citation: White PL, Posso R, Parr C, Price JS, Finkelman M, Barnes RA. The Presence of (1-->3)-beta-D-Glucan as Prognostic Marker in Patients After Major Abdominal Surgery. Clin Infect Dis. 2021 Oct 5;73(7):e1415-e1422. doi: 10.1093/cid/ciaa1370.
citation: Knitsch W, Vincent JL, Utzolino S, Francois B, Dinya T, Dimopoulos G, Ozgunes I, Valia JC, Eggimann P, Leon C, Montravers P, Phillips S, Tweddle L, Karas A, Brown M, Cornely OA. A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections. Clin Infect Dis. 2015 Dec 1;61(11):1671-8. doi: 10.1093/cid/civ707. Epub 2015 Aug 13.