Voriconazole And Anidulafungin Combination For Invasive Aspergillosis In Pediatric Subjects

Study Overview
=================
Brief Summary
-----------------
This study aims to compare the safety, tolerability, and efficacy of voriconazole and anidulafungin in combination versus voriconazole alone in pediatric subjects aged 2 to 17 years with invasive aspergillosis.

Official Title
-----------------
A Prospective, Randomized Trial Comparing The Safety, Tolerability, And Efficacy Of Voriconazole And Anidulafungin In Combination To That Of Voriconazole Alone When Used For Primary Therapy Of Invasive Aspergillosis in Pediatric Subjects Aged 2 to 17 Years

Conditions
-----------------
Aspergillosis, Invasive Pulmonary Aspergillosis, Neuroaspergillosis

Intervention / Treatment
-----------------
* Drug: Voriconazole
* Drug: Anidulafungin
* Drug: Voriconazole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of proven, probable, or possible invasive aspergillosis. Hematologic malignancy or allogeneic hematopoetic stem cell transplant. Exclusion Criteria: Sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis. Chronic invasive aspergillosis. Receipt of antifungal treatment for more than 96 hours. Severe liver dysfunction.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voriconazole and Anidulafungin Combination<br>Subjects in the combination arm will receive voriconazole and anidulafungin in combination for 2-4 weeks followed by voriconazole monotherapy to complete 6-12 weeks of therapy. | Drug: Voriconazole<br>* For Children aged 2-11 years and adolescents aged 12-14 years weighing <50 kg: Voriconazole 9 mg/kg IV load q12h x 24h, then 8 mg/kg IV q12h, with option to switch to oral voriconazole at 9 mg/kg q12h (maximum 350 mg) after 7 days. For adolescents aged 12-17 years, excluding 12-14-year-olds weighing <50kg: Voriconazole 6 mg/kg IV q12h x 24h, then 4 mg/kg IV q12h, with an option to switch to oral voriconazole at 200 mg q12h after 7 days. Voriconazole therapy is to be given for 6-12 weeks.<br>Drug: Anidulafungin<br>* Anidulafungin 3 mg/kg IV load q24h x 24h (maximum 200 mg), then 1.5 mg/kg q24h (maximum 100 mg). Anidulafungin therapy is to be given for 2-4 weeks in combination with voriconazole.<br>|
| Active Comparator: Voriconazole Monotherapy<br>Subjects in the monotherapy arm will receive voriconazole monotherapy for 6-12 weeks of therapy. | Drug: Voriconazole<br>* For Children aged 2-11 years and adolescents aged 12-14 years weighing <50 kg: Voriconazole 9 mg/kg IV load q12h x 24h, then 8 mg/kg IV q12h, with option to switch to oral voriconazole at 9 mg/kg q12h (maximum 350 mg) after 7 days. For adolescents aged 12-17 years, excluding 12-14-year-olds weighing <50kg: Voriconazole 6 mg/kg IV q12h x 24h, then 4 mg/kg IV q12h, with an option to switch to oral voriconazole at 200 mg q12h after 7 days. Voriconazole therapy is to be given for 6-12 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of voriconazole and anidulafungin in combination versus voriconazole alone as determined by rates of adverse events |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of all-cause mortality at 6 weeks |  | 6 weeks | 
| Rate of all-cause mortality at EOT |  | 12 weeks | 
| Global response to therapy at 6 weeks |  | 6 weeks | 
| Global response to therapy at EOT |  | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aspergillosis, Combination Therapy, Voriconazole, Anidulafungin