Contact information
Type
Scientific
Primary contact
Dr Oliver Cornely
ORCID ID
Contact details
University Hospital of Cologne
Department of Internal Medicine
Cologne
50924
Germany
+49 221 478 6209
oliver.cornely@uni-koeln.de
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NRA 150 0009
Study information
Scientific title
Acronym
Voriconazole prophylaxis
Study hypothesis
Voriconazole is superior to placebo in the prophylaxis of lung infiltrates until day 21 after start of induction chemotherapy.
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Condition
Acute Myelogenous Leukaemia (AML)
Intervention
Voriconazole 200 mg twice a day (bid) orally (po) or placebo
This trial was prematurely terminated on 19 January 2006 due to establishment of a new standard treatment, which made the placebo group of the trial ethically unjustifiable.
Intervention type
Drug
Phase
Phase III
Drug names
Voriconazole
Primary outcome measures
Incidence of lung infiltrates
Secondary outcome measures
1. Incidence of fever and other signs of infection
2. Incidence and type of documented bacteremia
3. Rate of patients with systemic open-label antifungal therapy
4. Time to initiation of systemic open-label antifungal therapy
5. Duration of absolute neutrophil count <500/µl
6. Rate and type of proven, probable and possible breakthrough invasive fungal infections
7. Rate of patients with fever of unknown origin
8. Incidence and severity of adverse events
9. Trough voriconazole plasma level
10. Direct costs of systemic antibiotics, antifungals and antivirals and diagnostic imaging
11. Overall costs in terms of the diagnosis related groups applied to the study patients
Overall trial start date
01/11/2004
Overall trial end date
31/12/2007
Reason abandoned
This trial was prematurely terminated on 19 January 2006 due to establishment of a new standard treatment, which made the placebo group of the trial ethically unjustifiable.
Eligibility
Participant inclusion criteria
Patients with first induction chemotherapy for acute myelogenous leukaemia (AML):
1. Newly diagnosed or relapsed, de novo or secondary AML
2. First induction chemotherapy cycle
3. Expected neutropenic phase of a minimum duration of 10 days
4. Age greater than 18 years
5. Legally signed informed consent
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
Planned: 150 patients, analyzed: 25 patients.
Participant exclusion criteria
1. Known proven, probable or possible invasive fungal infection at randomization or in patient history
2. CT with any signs of a fungal infection according to the EORTC/MSG criteria, i.e. with any infiltrate (Ascioglu, et al 2002)
3. Any current fever unless explained by non-infectious causes
4. Antibacterial prophylaxis other than TMP/SMX
5. LFT (AST/ALT/bilirubin) more than 3x the upper normal limit
6. Subjects who are receiving and cannot discontinue one of the following drugs at least 24 hours prior to randomization:
6.1. Drugs with a known possibility of QTc prolongation (e.g. terfenadine, astemizole, cisapride, pimozide, quinidine)
6.2. Drugs whose plasma levels may be increased by voriconazole therapy (e.g. sulphonylureas, ergot alkaloids, sirolimus, vinca alkaloids)
7. Subjects who have received the following drugs within 14 days prior to randomization: Potent inducers of hepatic enzymes that will reduce voriconazole levels (e.g. rifampicin, carbamazepine and barbiturates)
8. Concomitant therapy with absorbable antifungals
9. Patient has a diagnosis of acute hepatitis or cirrhosis due to any cause
10. Known hypersensitivity or other contraindication to voriconazole
11. Patient unwilling or unable to comply with the protocol
12. Diseases or disabilities preventing the patient from participating in the trial
13. Females of childbearing potential without negative serum pregnancy test at baseline or within 72 hours prior to start of study drug
Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, Denning DW, Donnelly JP, Edwards JE, Erjavec Z, Fiere D, Lortholary O, Maertens J, Meis JF, Patterson TF, Ritter J, Selleslag D, Shah PM, Stevens DA, Walsh TJ; Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer; Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002 Jan 1;34(1):7-14.
Recruitment start date
01/11/2004
Recruitment end date
31/12/2007
Locations
Countries of recruitment
Germany
Trial participating centre
University Hospital of Cologne
Cologne
50924
Germany
Funders
Funder type
Industry
Funder name
Pfizer GmbH, Karlsruhe (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary