Individualisation of Voriconazole Antifungal Therapy Antifungal Therapy (PIVOTAL)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||PIVOTAL: Pharmacological Individualisation of VOriconazole Therapy for AntifungaL Treatment|
- Dose adjustment success [ Time Frame: Day 5 of treatment ] [ Designated as safety issue: No ]Dose adjustment success will be evaluated by plasma trough concentration on day 5, successful dose adjustment is defined as a trough concentration of 1-3 mg/L of voriconazole.
- Mortality of patients [ Time Frame: 35 Day after starting treatment ] [ Designated as safety issue: Yes ]To examine the mortality of patients receiving individualised voriconazole dosing
- Toxicity [ Time Frame: Day 5 of treatment and 35 day follow-up ] [ Designated as safety issue: Yes ]To evaluate the adverse events that are attributable to voriconazole as assessed by CTCAE v4.
|Study Start Date:||September 2014|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
Standard adult Voriconazole (VFEND) Loading (1 hr infusion): 6mg/kg at 1 hour and 12 hours on day 1. Followed by standard maintenance dose 4mg/kg at 1 hour and 12 hours on day 2 (1 hour infusion). Day 3 follows the same schedule, expect the dose is adjusted, this dose is used on Day 4 and a further dose adjustment is made that is administered as above on Day 5.
voriconazole will be administered in iv form
Other Name: voriconazole
Invasive fungal infections are a major cause of morbidity and mortality in patients with haematological malignancy and haematopoietic stem cell transplantation.
Voriconazole is routinely used as a first-line agent for the treatment of invasive aspergillosis, invasive fusariosis and scedosporiosis. Voriconazole has extreme pharmacokinetic variability. Adult patients with a trough concentration of < 1 mg/L have a lower probability of clinical response whereas patients with trough concentrations > 6 mg/L a higher probability of toxicity.
Therapeutic drug monitoring for dose adjustment is advocated but there are no algorithms that enable voriconazole dosage to be reliably adjusted to achieve desired trough concentrations in a timely and optimally precise manner.
Novel ways to deliver optimised antifungal therapy are urgently required and this trial will evaluate whether giving a patients a tailored dose of voriconazole is safe and effective.
Plasma concentrations will be taken in real time and inputted in dose software that will calculate an optimum dose for the required trough concentration of 1-3 mg/L.
The software has been developed using data from phase I and III trials of voriconazole.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01887457
|The Christie NHS Foundation Trust|
|Manchester, United Kingdom, M20 4BX|
|Study Chair:||William Hope||University of Liverpool|