CRITIC - Treatment of Candidemia and Invasive Candidiasis (CRITIC)

CRITIC: Phase II Pilot Multicenter Study on Efficacy and Safety of Liposomal Amphotericin B (AmBisome®) at 2 mg/kg/Day in the Treatment of Candidemia and Invasive Candidiasis in Non-Neutropenic Patients

Patients will receive 2mg/kg/day IV daily administration of AmBisome® over 30-60 minutes as a reaction to signs/symptoms and positive Candida culture

Study Overview

• Status: Completed
• Conditions: Candidemia; Invasive Candidiasis
• Intervention / Treatment: Drug: AmBisome

Detailed Description

Subjects will be enrolled to receive intravenously AmBisome® at 2 mg/kg/day for a maximum of 4 weeks. Treatment will be discontinued in case of failure, adverse events precluding treatment or success. In case of success AmBisome® at 2 mg/kg/day should be administered for at least 5 days after the complete resolution of all clinical findings of an active infection or for at least 8 days after the last positive blood culture or culture from a normally sterile site. It is not recommended to declare failure (and therefore change treatment) before giving at least 5 days of antifungal therapy. Failures in patients given less than 5 days of treatment should be well documented (e.g. persistent positive cultures despite catheter removal, clinical deterioration in absence of any explanation other than the fungal infection). Follow-up evaluations will be conducted at 2 and 4 weeks after the end of AmBisome® therapy. At end of treatment (time point for success or failure) patients may be shifted to oral (not intravenous) antifungals at the discretion of the local investigator, once a complete response has been achieved, if secondary prophylaxis is deemed necessary.

• Study Type: Interventional
• Enrollment (Anticipated): 39
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20146
    • Gilead Sciences Srl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients admitted to ICU for all medical reasons that meet the inclusion criteria
• Males or non pregnant females (women of child-bearing potential must have a negative serum or urine pregnancy test at baseline).
• Subjects who are 14 years old or older.
• Subjects with at least one positive blood culture isolation of a Candida spp. from a specimen or from a normally sterile site (including abdominal catheters), drawn within 96 hours prior to study entry.

• Subjects who have clinical evidence of infection AT SOME TIME WITHIN 48 HOURS PRIOR TO ENROLLMENT, including AT LEAST ONE of the following:

  1. temperature> 38°C on 2 occasions at least 4 hours apart or one determination greater than 38.5°C (internal, at oesophagus, tympani or bladder levels).
  2. systolic blood pressure < 90, or a >30 mm Hg decrease in systolic BP from the subject's normal baseline.
  3. Signs of inflammation (swelling, heat, erythema, purulent drainage) from a site infected with Candida
• Subjects or their legal representative (but the subject should sign it in any case when able to) must sign a written informed consent form. Written informed consent must be obtained before any study-related procedure is carried out.

Exclusion Criteria:

• Subjects with a history of allergy or intolerance to AmBisome®
• Subjects who have received systemic antifungal therapy within 15 days prior to inclusion in the study
• Any severe cardiovascular disease (such as arrhythmias, in particular) which may constitute a contra-indication to AmBisome® administration
• Subjects with an absolute neutrophil count of less than 500/mm3 in the 48 hours before enrolment in the study
• Subjects with a diagnosis of AIDS (positive HIV serology in association with either CD4 cell counts < 200 cells/mm3or history of an opportunistic infection /neoplasm), aplastic anemia, or Chronic Granulomatous Disease.

• Subjects with moderate or severe liver disease defined as any one or more of the following:

  * Alkaline phosphatase, ALT, AST, or total bilirubin greater than 5 times the ULN (upper limit of normal)

• Subjects with a severe renal impairment defined by a serum creatinine of more than 2.5 mg/dL.
• Women who are pregnant or breastfeeding.
• Subjects who are unlikely to survive more than 24 hours.
• Subjects who previously participated in this study.
• Subjects who have received within the two weeks before study entry, are receiving or likely to receive any investigational drug (unlicensed new chemical entity).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; AmBisome® 2 mg/kg/day in a unique daily IV administration	Drug: AmBisome; Patients will receive 2mg/kg/day IV daily administration of AmBisome® over 30-60 minutes as a reaction to signs/symptoms and positive Candida culture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Success at End of Trial (EOT) - Success is defined as: The definition of success is (criteria a, b, c and d must be satisfied): a. i) Absence of all clinical signs and symptoms present at baseline and absence of any new signs and symptoms that may be	Through 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy at the 2nd and 4th week after the end of therapy	Through 4th week
Safety of the 2 mg/kg/day regimen	Through 4 weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Luigi Picaro, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (ACTUAL): December 1, 2008
• Study Completion (ACTUAL): January 1, 2009

Study Registration Dates

• First Submitted: April 29, 2008
• First Submitted That Met QC Criteria: May 1, 2008
• First Posted (ESTIMATE): May 2, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): March 27, 2009
• Last Update Submitted That Met QC Criteria: March 26, 2009
• Last Verified: March 1, 2009

More Information

Terms related to this study

• Keywords: candidemia; Ambisome; invasive candidiasis; liposomal amphotericin B
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Mycoses; Invasive Fungal Infections; Fungemia; Candidiasis; Candidemia; Candidiasis, Invasive; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Liposomal amphotericin B
• Other Study ID Numbers: GS-IT-131-0177