Efficacy of Interferon-gamma in Combination With Anidulafungin for the Treatment of Candidemia

A Multicentre, Prospective, Randomized Open-label Pilot Study to Assess the Feasibility and Preliminary Efficacy of Interferon-gamma in Combination With Anidulafungin for the Treatment of Candidemia

The purpose of this study is to assess the feasibility and preliminary efficacy of interferon-gamma in combination with anidulafungin for the treatment of candidemia

Study Overview

• Status: Unknown
• Conditions: Candidemia
• Intervention / Treatment: Drug: Interferon-gamma, Recombinant

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Corine Delsing, MD; Phone Number: +31-24-3618819; Email: C.Delsing@aig.umcn.nl
• Study Contact Backup: Name: Mihai Netea, MD. PhD; Phone Number: +31-24-3618819; Email: M.Netea@AIG.umcn.nl

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • Radboud University Medical Centre Nijmegen
    • Contact: Corine Delsing, MD; Phone Number: +31-24-3618819; Email: C.Delsing@aig.umcn.nl
    • Principal Investigator: Corine Delsing, MD
    • Sub-Investigator: Chantal Bleeker-Rovers, MD, PhD
    • Sub-Investigator: Mihai Netea, MD, PhD
    • Sub-Investigator: Bart Jan Kullberg, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or non-pregnant females (who must agree to use barrier methods of contraception during the study therapy period, women of childbearing age must have a negative urine pregnancy or serum test at baseline).
• Subjects who are 18 years of age or older
• Subjects with at least one positive blood culture isolation of Candida species from a specimen drawn within 96 hours prior to study entry.

• Subjects who have clinical evidence of infection AT SOME TIME WITHIN 96 HOURS PRIOR TO ENROLLMENT, including AT LEAST ONE of the following:

  • Temperature >37.8 ˚C on 2 occasions at least 4 hours apart or one measurement > 38.2 ˚C
  • Systolic blood pressure <90 or a >30 mmHg decrease in systolic BP from the subject's normal baseline.
  • Signs of inflammation (swelling, heat, erythema, purulent drainage) from a site infected with Candida (eg, joint, skin, eye, bone, esophagus)
  • Radiologic findings of invasive candidiasis
• Subject or their legal representative must sign a written informed consent form.

Exclusion Criteria:

• Subjects with a history of allergy or intolerance to echinocandins or IFNgamma
• Subjects with a history of documented epileptic seizures
• Subjects with severe renal impairment (creatinine clearance less than 30/mL/min)
• Subjects with severe liver failure (impaired synthesis of proteins such as coagulation factors manifested by increased prothrombin time)
• Subjects with an absolute neutrophil count of less than 500/mm3 at study entry
• Women who are pregnant or lactating
• Subjects who are unlikely to survive more than 24 hours
• Subjects who have failed previous systemic antifungal therapy for the Candida spp. infection which is being studied.
• Subjects who have received more than 48 hours of systemic antifungal therapy for the current episode, within 96 hours prior to study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Interferon-gamma	Drug: Interferon-gamma, Recombinant; Interferon 50 mcg/m2 to be administered three times per week during two weeks
NO_INTERVENTION: No intervention; No adjunctive treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the time to negative blood cultures	at fixed time points during follow up (at least until 8 weeks after end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival		until 8 weeks after end of treatment
time to death		Until 8 weeks after end of treatment
outcome of fungal infection	resolution at week 2 and 8 after end of treatment, patient status at end of therapy, microbiological parameters	Until 8 weeks after end of treatment
duration of antifungal therapy		Until end of treatment
duration of hospitalization		Until end of hospitilization
immunological parameters		Until 8 weeks after end of treatment
tolerability and safety		until 8 weeks after end of treatment

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: BioMérieux
• Investigators: Study Director: Mihai Netea, MD PhD, Radboud University Medical Center; Principal Investigator: Corine Delsing, MD, Radboud University Medical Center

Publications and helpful links

General Publications

• Delsing CE, Gresnigt MS, Leentjens J, Preijers F, Frager FA, Kox M, Monneret G, Venet F, Bleeker-Rovers CP, van de Veerdonk FL, Pickkers P, Pachot A, Kullberg BJ, Netea MG. Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series. BMC Infect Dis. 2014 Mar 26;14:166. doi: 10.1186/1471-2334-14-166.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ANTICIPATED): January 1, 2013

Study Registration Dates

• First Submitted: January 4, 2011
• First Submitted That Met QC Criteria: January 4, 2011
• First Posted (ESTIMATE): January 5, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2012
• Last Update Submitted That Met QC Criteria: February 13, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: candidemia; invasive fungal disease; candida sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Mycoses; Invasive Fungal Infections; Fungemia; Candidiasis; Candidiasis, Invasive; Candidemia; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons; Interferon-gamma
• Other Study ID Numbers: Interferon-gamma 001; 2009-014600-66 (EUDRACT_NUMBER); NL28823.091.10 (OTHER: Dutch Central Committee on Research inv. Human Subjects)