A Randomized Study of a Short Duration Therapy for Candidemia (CANDISHORT)

Scientific justification Candidemia is a major public health problem. In France, the 30-day mortality of candidemia varies from 30% to 50% depending on the need for intensive care and it has not decreased in 30 years.

The duration of treatment for candidemia was set at a minimum of 14 days after the last positive blood culture following the Rex trial (1) comparing the efficacy of fluconazole vs amphotericin B where the minimum duration of treatment was imposed. The risk of a too short treatment is the absence of control of the candidemia with secondary dissemination, in particular cardiac and ophthalmic.

A retrospective study looking at the risk of ophthalmologic complications after candidemia found among the 21/78 treated for less than 14 days, only one case of late endophthalmitis in a patient who had only been treated for 48 hours. In addition, the prolonged duration of antifungals exposes the risk of selection of more resistant strains with a modification of the flora, with the possibility of acquiring resistance as early as 8 days of treatment with caspofungin, and has a greater liver toxicity.

There is no prospective study on the direct impact of antifungal agents (type of antifungal agent and duration) on the mycobiota.

Study Overview

• Status: Not yet recruiting
• Conditions: CANDIDEMIA
• Intervention / Treatment: Drug: Standard of Care (SOC); Drug: Shortened duration of antifungal therapy

• Study Type: Interventional
• Enrollment (Estimated): 362
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Blandine Denis, MD; Phone Number: +33 +33142494585; Email: blandine.denis@aphp.fr
• Study Contact Backup: Name: Jérôme Lambert, MD PhD; Phone Number: +33 +33 1 42 49 97 42; Email: jerome.lambert@u-paris.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults (Age ≥ 18 years old)
• With an uncomplicated candidemia defined by the absence of secondary sites requiring prolonged treatment: endocarditis, ophthalmologic involvement, thrombosed catheter, arthritis, meningitis, candida abscess that cannot be drained, pyelonephritis.
• Without expected aplasia duration greater than 7 days
• Being apyretic and having a 1st negative blood culture after diagnosis
• Removal of the vascular catheter if present
• Written informed consent from the patients or his/her relatives
• Patients with less than 7 days of aplasia predictable

Exclusion Criteria:

• Presence of an indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained and is likely to be the source of candidemia or the presence of secondary sites of candidemia requiring prolonged treatment
• Patients with more than 7 days of aplasia
• Candida strain resistant to the antifungal used
• Pregnancy, breastfeeding
• Hypersensitivity or previous severe adverse drug reaction to the antifungal treatments.
• unwilling, in the judgment of the investigator, to comply with the protocol
• Patient under legal guardianship or without healthcare coverage
• Women with childbearing potential not using adequate contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 14 days of antifungal treatment	Drug: Standard of Care (SOC); 14 days of antifungal therapy after the 1st negative blood culture
Experimental: 7 days of antifungal treatment	Drug: Shortened duration of antifungal therapy; 7 days of antifungal therapy after the 1st negative blood culture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality (ACM)	at day 28 after the 1st negative blood culture under antifungal treatment for all patients included with an uncomplicated candidemia	At day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with secondary localizations		At day 28
Cumulative incidence of death related to fungal infection	at Day 28 after the 1st negative blood culture under antifungal treatment	At day 28
Aspartate Amino-transferase level		At day 14
Aspartate Amino-transferase level		At day 28
alanine aminotransférase (ALAT) level		At day 14
alanine aminotransférase (ALAT) level		At day 28
Gamma-Glutamyl Transférase (GGT) level		At day 14
Gamma-Glutamyl Transférase (GGT) level		At day 28
Bilirubin blood levels		At day 14
Bilirubin blood levels		At day 28
Cost per extra-day alive without antifungal treatment	Incremental cost effectiveness ratio	Up to day 28

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: February 28, 2025
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Invasive Fungal Infections; Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Mycoses; Candidiasis, Invasive; Candidiasis; Fungemia; Candidemia; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Anti-Infective Agents, Local; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; 14-alpha Demethylase Inhibitors; Antifungal Agents; Clotrimazole; Miconazole
• Other Study ID Numbers: APHP230824

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No