INVASIVE ASPERGILLOSIS MedDRA version: 9.1 Level: PT Classification code 10003488 Term: Aspergillosis
Conditions
Interventions
Trade Name: Ecalta
Product Name: Anidulafungin
Product Code: PF-03910960
Pharmaceutical Form: Intravenous infusion
CAS Number: 166663-25-8
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
Pfizer Inc., 235 East 42nd Street, New York, NY 10017
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Immunocompromised state due to either: ? Receipt of allogeneic hematopoietic stem cell transplantation after myeloablative or non-myeloablative conditioning; or, ? Hematologic malignancy (excluding subjects with progressive hematologic disease who have not responded (or are not likely to respond) to treatment); 2. Diagnosis of proven or probable or possible invasive aspergillosis (based on a modified version of the revised EORTC/MSG consensus definitions); ? NOTE: Subjects enrolled with possible IA will be required to have a proven or probable diagnosis established based on tests done within 7 days of enrollment (See Section 6.6). Proven invasive aspergillosis is defined as: ? Histopathologic, cytopathologic, or direct microscopic examination of a needle aspiration or biopsy showing hyphal forms with evidence of associated tissue damage (either microscopically or as an infiltrate or lesion by imaging); or, ? Recovery of Aspergillus species by culture from a sample obtained by a sterile procedure from normally sterile and clinically or radiologically abnormal site consistent with an infectious disease process, excluding BAL, cranial sinus cavity, and urine. Probable invasive aspergillosis is defined by at least: ? One host factor; and; ? One clinical criterion; and; ? One microbiologic criterion. Possible invasive aspergillosis is defined by at least: ? One host factor; and; ? One clinical criterion. 3. Male or female greater than or equal to 16 years of age; 4. For women of childbearing potential, patient has had a negative pregnancy test. 5. Evidence of a personally signed and dated informed consent document in accordance with local regulatory and legal requirements indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. 6. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the trial: 1. Known history of allergy, hypersensitivity or serious reaction to azole or echinocandin antifungals; 2. Female patients who are pregnant or lactating; 3. Patients with sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA); 4. Patients with chronic invasive aspergillosis with a duration of symptoms or radiological finding for more than 4 weeks prior to study entry; 5. Patients who are receiving and cannot discontinue the following drugs at least 24 hours prior to randomization: terfenadine, astemizole, cisapride, pimozide or quinidine (because of the possibility of QT prolongation); 6. Patients receiving any of the following medications: sirolimus, rifampin, rifabutin, carbamazepine, long-acting barbiturates (eg, phenobarbital, mephobarbital), ritonavir, efavirenz, or ergot alkaloids (eg, ergotamine, dihydroergotamine); 7. There are other potentially clinically relevant interactions between voriconazole and some commonly prescribed drugs. While these drugs have not been contraindicated, advice on monitoring or dosage adjustments is made. 8. Receipt of systemic antifungal treatment for the current episode of invasive aspergillosis for a duration of greater than 96 hours. NOTE: Patients receiving mold-active prophylaxis may be enrolled provided that they meet criteria for proven or probable IA at the time of enrollment. 9. Severe liver dysfunction (defined as total bilirubin >10x upper limit of normal, or AST, ALT, or alkaline phosphatase >5x upper limit of normal). Local laboratory results may be used to qualify individuals for enrollment. However, if laboratory values drawn at the Baseline visit exceed the above limits for exclusion, the medical monitor must be contacted without delay to discuss continuation of study treatment; 10. Patients on artificial ventilation; 11. Patients with any condition which, in the opinion of the investigator, could affect patient safety, preclude evaluation of response, or make it unlikely that the proposed course of therapy can be completed; 12. Patients who are receiving, or are likely to receive, any Phase I investigational drug. Patients receiving Phase II or Phase III investigational drugs may be enrolled only with the prior approval of the medical monitor. Patients receiving investigational drugs that are currently licensed for other indications may be enrolled; 13. The inclusion of a patient more than once in this trial is not permissible; 14. Patients not expected to survive for at least 5 days or who have a Karnofsky score <20 (See Appendix 4); 15. Patients with a high likelihood of death due to factors unrelated to aspergillosis (eg, due to relapsed malignancy, severe graft versus host disease, other underlying diseases, etc.) within 30 days following planned enrollment (investigator's discretion); 16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study; 17. Concomitant administration of systemic agents active against Aspergillus species is not permissible.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare all cause mortality at 6 weeks in patients with hematologic malignancy or with allogeneic HSCT with a diagnosis of proven or probable IA receiving voriconazole and anidulafungin in combination versus voriconazole monotherapy.;Secondary Objective: • To compare (global response) and (mortality due to IA) at 6 weeks; • To compare all cause mortality at 6 weeks and 12 weeks in patients with hematologic malignancyor with allogeneic HSCT with a diagnosis of possible, proven or probable IA (ITT population) receiving the combination of voriconazole and anidulafungin to voriconazole monotherapy; • To compare time to death due to (IA ) and (all causes) in patients mentioned in third bullet • To compare the safety and tolerability of voriconazole monotherapy to that of voriconazole in combination with anidulafungin; ;Primary end point(s): The primary endpoint is all cause mortality, measured 6 weeks after IA diagnosis in subjects with proven or probable IA. | — |
Countries
Austria, Belgium, Czech Republic, France, Germany, Greece, Ireland, Italy, Portugal, Spain, United Kingdom
Outcome results
None listed