A Study to Evaluate Pre-emptive Treatment for Invasive Candidiasis in High Risk Surgical Subjects (INTENSE)

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

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.

Study Overview

• Status: Completed
• Conditions: Mycoses
• Intervention / Treatment: Drug: micafungin; Drug: placebo

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)

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
  • Salzburg, Austria, 5020
  • Wien, Austria, 1030
  • Wien, Austria, 1090
• Belgium
  • Brussels, Belgium, 1200
  • Brussels, Belgium, 1070
  • Edegem, Belgium, 2650
  • Gent, Belgium, 9000
  • Liege, Belgium, 4000
• Denmark
  • Viborg, Denmark, 8800
• Finland
  • Jyvaskyla, Finland, 40620
  • Kuopio, Finland, 70210
  • Tampere, Finland, 33521
• France
  • Amiens, France, 84054
  • La Roche sur Yon Cedex 9, France, 85925
  • Limoges, France, 87042
  • Paris, France, 75679
  • Paris Cedex 14, France, 75674
  • Pierre Benite, France, 69495
  • Poitiers, France, 86021
• Germany
  • Freiburg, Germany, 79106
  • Hannover, Germany, 30625
  • Koln, Germany, 50937
  • Leipzig, Germany, 04103
  • Lubeck, Germany, 23562
• Greece
  • Athens, Greece, 12461
  • Thessaloniki, Greece, 57010
  • Thessaloniki, Greece, 57001
• Hungary
  • Debrecen, Hungary, 4032
  • Gyor, Hungary, 9023
  • Szeged, Hungary, 6720
• Israel
  • Ramat Gan, Israel, 52621
  • Tel Aviv, Israel, 64239
• Italy
  • Bologna, Italy, 40138
  • Milano, Italy, 20142
  • Monza, Italy, 20052
  • Pisa, Italy, 56126
  • Roma, Italy, 00161
  • Roma, Italy, 00168
  • Verona, Italy, 37126
• Romania
  • Bucharest, Romania, 50098
  • Oradea, Romania, 410168
  • Timisoara, Romania, 300748
• Spain
  • Barcelona, Spain, 08003
  • Madrid, Spain, 28006
  • Madrid, Spain, 28046
  • Valencia, Spain, 46014
  • Valladolid, Spain, 47012
• Switzerland
  • Lausanne, Switzerland, 1011
• Turkey
  • Ankara, Turkey, 06100
  • Ege, Turkey, 35100
  • Eskisehir, Turkey, 26480
  • Trabzon, Turkey, 61080
• United Kingdom
  • Blackpool, United Kingdom, FY3 8NR
  • Leeds, United Kingdom, LS1 3EX
  • Leeds, United Kingdom, LS9 7TF

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 Micafungin; IV	Drug: micafungin; IV; Other Names: FK463; mycamine
Placebo Comparator: 2 Placebo; IV	Drug: placebo; IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of Invasive Fungal Infection	During treatment
Time from baseline to the first confirmation of Invasive Fungal Infection	Baseline to End of Treatment visit

Secondary Outcome Measures

Outcome Measure	Time Frame
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)	At the EOT visit
The emergence or persistence of fungal colonization	At the EOT visit
The level of organ dysfunction	At the EOT visit
To assess the requirement for additional abdominal surgery/intervention.	At the End of Study visit
Organ failure-free days	From Day 1 until 28 days after end of study drug treatment
Fungal-free survival	From Day 1 until 28 days after end of study drug treatment
Intensive Care Unit (ICU)-free days	From Day 1 until 28 days after end of study drug treatment
All-cause mortality	At the End of Study and Long-Term Follow Up visit
Health-related quality of life	At the End of Study visit
Assessment of the safety of micafungin when used as a pre-emptive treatment	At the End of Study visit

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Chair: Use Central Contact, Astellas Pharma Europe Ltd.

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Link to results on the Astellas Clinical Study Results website.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2010
• Primary Completion (Actual): December 15, 2011
• Study Completion (Actual): December 15, 2011

Study Registration Dates

• First Submitted: May 10, 2010
• First Submitted That Met QC Criteria: May 12, 2010
• First Posted (Estimated): May 13, 2010

Study Record Updates

• Last Update Posted (Actual): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 15, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Micafungin; intra-abdominal surgery; invasive fungal infection; mycoses; intra-abdominal infection
• Additional Relevant MeSH Terms: Invasive Fungal Infections; Infections; Bacterial Infections and Mycoses; Mycoses; Candidiasis; Candidiasis, Invasive; Anti-Infective Agents; Antifungal Agents; Micafungin
• Other Study ID Numbers: 9463-EC-0002; 2008-006409-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR