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Individualisation of Voriconazole Antifungal Therapy Antifungal Therapy

Information source: Christie Hospital NHS Foundation Trust
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Immunocompromised Patient; Aspergillosis; Fusarium

Intervention: VFEND (Drug)

Phase: Phase 2

Status: Suspended

Sponsored by: Colin Lunt

Official(s) and/or principal investigator(s):
William Hope, Study Chair, Affiliation: University of Liverpool

Summary

This is a trial to determine whether giving a patient a tailored dose of voriconazole is safe and effective.

Clinical Details

Official title: PIVOTAL: Pharmacological Individualisation of VOriconazole Therapy for AntifungaL Treatment

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Dose adjustment success

Secondary outcome:

Mortality of patients

Toxicity

Detailed description: 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Any adult ≥18 years old

- Patients where a new course of voriconazole is indicated for suspected or confirmed

invasive aspergillosis or other serious fungal infections that is deemed by the treating physician to be susceptible to voriconazole

- Patients must have venous access to permit the administration of voriconazole and

enable the procurement of multiple plasma samples to measure voriconazole concentrations.

- Estimated creatinine clearance ≥ 50 mL/min

- Able to give written informed consent

- Considered fit to receive the trial treatment

- Able to remain in the hospital for at least 5 days or until they complete their trial

treatment

- Female patients must satisfy the investigator that they are not pregnant, or are not

of childbearing potential, or are using adequate contraception

- Men must also use adequate contraception

Exclusion Criteria:

- Patients with an estimated creatinine clearance < 50 mL/minute (this precludes the

use of intravenous voriconazole)

- Patients receiving any form of renal replacement therapy i. e. haemodialysis or

haemofiltration

- Patients with hepatic insufficiency

- Female patients that are pregnant, breast feeding or planning pregnancy during the

study

- Past history of intolerance to voriconazole

- Age <18

- Evidence of a clinically relevant fungal isolate that is resistant to voriconazole

- QT prolongation on ECG

- Use of other medications that contraindicate the use of voriconazole

- Patients receiving any other medications that are contraindicated with the use of

voriconazole i. e. terfenadine, long acting barbiturates, ergot alkaloids, etc. (Refer to SMPC). Only patients on rifampicin, rifabutin, phenytoin, and carbamazepine would have voriconazole precluded. Voriconazole influences with the pharmacokinetics of many additional agents- (see SMPC)- most importantly anti-rejection compounds- cyclosporine, tacrolimus]

- Uncontrolled cardiac, respiratory or other disease or any serious medical or

psychiatric disorder that would preclude trial therapy or informed consent.

- Hypersensitivity to Voriconazole, its excipients or other triazoles

Locations and Contacts

The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
Additional Information

Christie NHS website

Starting date: September 2014
Last updated: June 16, 2014

Page last updated: August 23, 2015

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