Individualisation of Voriconazole Antifungal Therapy Antifungal Therapy

NCT ID: NCT01887457

Last Updated: 2015-10-07

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2016-12-31

Brief Summary

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

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.

Conditions

Immunocompromised Patient; Aspergillosis; Fusarium

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Voriconazole

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.

Group Type: EXPERIMENTAL

VFEND

Intervention Type: DRUG

voriconazole will be administered in iv form

Interventions

VFEND

voriconazole will be administered in iv form

Intervention Type: DRUG

Other Intervention Names

voriconazole

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Christie NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Brynn Chappell

OTHER

Sponsor Role: lead

Responsible Party

Brynn Chappell

Clinical Trials Project Manager

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

William Hope

Role: STUDY_CHAIR

University of Liverpool

Locations

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

United Kingdom

Related Links

http://www.christie.nhs.uk/

Christie NHS website

Other Identifiers

2013-002578-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

13_DOG06_172

Identifier Type: -

Identifier Source: org_study_id