CRITIC - Treatment of Candidemia and Invasive Candidiasis

Condition(s) targeted: Candidemia; Invasive Candidiasis

Intervention: AmBisome (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Gilead Sciences

Official(s) and/or principal investigator(s):
Pier Luigi Carriero, Study Director, Affiliation: Gilead Sciences

Overall contact:
Loredana Balzano, Phone: +39 02 43920239, Email: RosariaLoredana.Balzano@gilead.com

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

Official title: 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

Study design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: 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

Secondary outcome:

Efficacy at the 2nd and 4th week after the end of therapy

Safety of the 2 mg/kg/day regimen

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.

Minimum age: 14 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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).

Loredana Balzano, Phone: +39 02 43920239, Email: RosariaLoredana.Balzano@gilead.com

Gilead Sciences Srl, Milan 20146, Italy; Recruiting
Pier Luigi Carriero, Phone: +39 02 43920231, Email: PierLuigi.Carriero@gilead.com

Starting date: May 2007
Ending date: July 2009
Last updated: November 11, 2008