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 |
| Secondary identifying numbers | NRA 150 0009 |
- 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
Scientific
University Hospital of Cologne
Department of Internal Medicine
Cologne
50924
Germany
| Phone | +49 221 478 6209 |
|---|---|
| oliver.cornely@uni-koeln.de |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Voriconazole |
| Primary outcome measure | 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 study start date | 01/11/2004 |
| 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 number of participants | Planned: 150 patients, analyzed: 25 patients. |
| 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
50924
Germany
Sponsor information
University Hospital of Cologne (Germany)
Hospital/treatment centre
Hospital/treatment centre
Kerpener Strasse 62
Cologne
50924
Germany
"ROR" |
https://ror.org/05mxhda18 |
|---|
Funders
Funder type
Industry
Pfizer GmbH, Karlsruhe (Germany)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
