None listed
Conditions
Interventions
Group 1 Type of group
First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin 100 mg IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy
First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV BID plus anidulafungin placebo IV qd. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin placebo IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin placebo IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.
Sponsors
PFIZER S.A.,
Eligibility
Age
16 Years to 80 Years
Inclusion criteria
Inclusion criteria: • Immunosuppressed status due to: Reception of allogeneic hematopoietic stem cell transplantation after myeloablative or non-myeloablative conditioning; Malignant haematological disease (excluding participants with progressive hematological disease who have not responded (or probably do not respond) to treatment); • Diagnosis of proven or probable or possible aspergillosis (based on a modified version of the revised EORTC / MSG consensus definitions, see Annex 1); • Men or women> 16 years of age; • In the case of women of childbearing age, the patient has been negative in the urine pregnancy test. • Proof of a signed and personally dated informed consent document in accordance with local legal provisions that indicate that the participant (or a legally acceptable representative) has been informed of all aspects related to the study. • Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Exclusion criteria
Exclusion criteria: • Known history of allergy, hypersensitivity or serious reaction to azole or echinocandin antifungals; • Patients who are pregnant or breastfeeding; • Patients with sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA); • Patients with chronic invasive aspergillosis with a duration of symptoms or radiological findings for more than 4 weeks before entering the study; • Patients who are receiving and can not discontinue the use of the following drugs at least 24 hours before randomization: terfenadine, astemizole, cisapride, pimozide or quininidine (due to the possibility of QT prolongation); • Patients receiving one of the following medications: sirolimus, rifampin, rifabutin, carbamazepine, long-acting barbiturates (eg phenobarbital, mephobarbital), ritonavir, efavirenz, or ergot alkaloids eg, ergotamine, dihydroergotamine); • There are other potentially clinically relevant interactions between voriconazole and some drugs that are prescribed regularly. Although these drugs are not contraindicated, it is advisable to monitor or adjust the dosage, as described in Annex 2. • The reception of 4 or more days of systemic antifungal treatment for the current episode of invasive aspergillosis. • Severe hepatic dysfunction (defined as total bilirubin> 10x upper limit of normal, or AST, ALT, alkaline phosphatase> 5x upper limit of normal). The results of the local laboratory can be used to qualify the participants for enrollment. However, if the laboratory values ​​obtained in the Baseline visit exceed the above limits for exclusion, the medical monitor should be contacted without delay to discuss the continuation of the study treatment; • Patients with artificial ventilation; • Patients with any clinical condition that, in the opinion of the investigator, may affect patient safety, impede the evaluation of the response, or make it unlikely that the proposed course of therapy can be completed; • Patients who are receiving, or likely to receive, any Phase 1 research drug. Patients receiving Phase II or Phase III research drugs may only enroll with the prior approval of the medical monitor. Patients can be enrolled • To receive research drugs that are currently authorized for other indications; • Inclusion of a patient more than once in this study is not allowed; • Patients who are not expected to survive for at least 5 days or who already have a Kamofsky score of <30 • Patients with a high probability of death due to factors unrelated to aspergillosis (for example, due to a recurrent malignancy, severe graft-versus-host disease, other underlying diseases, etc.) within 30 days after to the planned enrollment (at the investigator´s discretion); • Another severe, acute or chronic medical or psychiatric condition or laboratory test with an abnormal result that could increase the risk associated with participation in the study or administration of investigational products or that could interfere with the interpretation of the results of the study and , in the opinion of the researcher, may make the participant unsuitable to enter this study; • Concomitant administration of systemic agents active against Aspergillus species is not allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:The primary significance test will be carried out on the difference of mortality rates in the two treatment arms, adjusted for the randomization stratum, using the normal approximation to the binomial distribution. Measure:Mortality from all causes, evaluated at the end of the 6 weeks of treatment Timepoints:6 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:The overall response to treatment, which incorporates both clinical and radiological responses. It will be qualified in complete response, partial response, stable and fails. Measure:Global response after 6 weeks Timepoints:6 weeks ; Outcome name:Participants will be contacted (phone, mail or email) to determine the survival status in Week 6 (if they are no longer hospitalized) Measure:Mortality from all causes after 6 weeks in participants with possible, probable or proven AI (ITT population) Timepoints:Week 6 ; Outcome name:Participants will be contacted (phone, mail or email) to determine the survival status in Week 12 (if they are no longer hospitalized) Measure:Mortality from all causes after 12 weeks in participants with probable or proven AI Timepoints:12 weeks ; Outcome name:Participants will be contacted (phone, mail or email) to determine the survival status in Week 6 (if they are no longer hospitalized) Measure:Mortality due to AI after 6 weeks Timepoints:6 weeks ; Outcome name:Participants will be contacted (phone, mail or email) to determine the survival status in Week 6 (if they are no longer hospitalized) Measure:Survival time (mortality from all causes) Timepoints:During the study ; Outcome name:Participants will be contacted (phone, mail or email) to determine the survival status in Week 6 (if they are no longer hospitalized) Measure:Survival time due to AI Timepoints:During the study ; Outcome name:Adverse events: Intercurrent diseases will be reported (for example, graft-versus-host disease, graft rejection, cytomegalovirus disease, etc.) and surgical procedures. • Lab tests. • Blood tests will be performed at all visits; • Urine pregnancy tests will be performed on all women of childbearing age in Basal and on Day 42 (Week 6). Measure:Safety and tolerability of voriconazole monotherapy compared to the combination of voriconazole | — |
Countries
Arabia Saudi, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, France, Germany, Greece, India, Italy, Korea South, Netherlands, Poland, Portugal, Russian Federation, Singapore, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kindgdom, United States
Contacts
Public ContactLuciana Obreros
PFIZER S.A.
Outcome results
None listed