Phase III study of safety, tolerance, efficacy, pharmacokinetics, and costs of therapy with voriconazole or placebo in the prophylaxis of lung infiltrates in patients undergoing induction chemotherapy for acute myelogenous leukaemia

ISRCTN	ISRCTN64013427
DOI	https://doi.org/10.1186/ISRCTN64013427
Protocol serial number	NRA 150 0009
Sponsor	University Hospital of Cologne (Germany)
Funder	Pfizer GmbH, Karlsruhe (Germany)

Submission date: 27/09/2004
Registration date: 05/01/2005
Last edited: 13/12/2007

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Oliver Cornely
Scientific

University Hospital of Cologne
Department of Internal Medicine
Cologne
50924
Germany

Phone	+49 221 478 6209
Email	oliver.cornely@uni-koeln.de

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	Voriconazole prophylaxis
Study objectives	Voriconazole is superior to placebo in the prophylaxis of lung infiltrates until day 21 after start of induction chemotherapy.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Voriconazole
Primary outcome measure(s)	Incidence of lung infiltrates
Key secondary outcome measure(s)	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
Completion date	31/12/2007
Reason abandoned (if study stopped)	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 type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target sample size at registration	150
Key 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
Key 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.
Date of first enrolment	01/11/2004
Date of final enrolment	31/12/2007

Locations

Countries of recruitment

Germany

Study participating centre

University Hospital of Cologne

Cologne
50924
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan