Individualisation of Voriconazole Antifungal Therapy Antifungal Therapy

Aspergillosis Clinical Trial

— PIVOTAL  

Official title:

PIVOTAL: Pharmacological Individualisation of VOriconazole Therapy for AntifungaL Treatment

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT01887457
• Other study ID #: 13_DOG06_172
• Secondary ID: 2013-002578-34
• Status: Suspended
• Phase: Phase 2
• First received: June 7, 2013
• Last updated: October 6, 2015
• Start date: September 2014
• Est. completion date: December 2016

Study information

• Verified date: October 2015
• Source: Christie Hospital NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 33
• Est. completion date: December 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Aspergillosis
• Fusarium
• Immunocompromised Patient

Intervention

Drug:
• VFEND
voriconazole will be administered in iv form

Locations

Country	Name	City	State
United Kingdom	The Christie NHS Foundation Trust	Manchester

Sponsors (2)

Lead Sponsor	Collaborator
Brynn Chappell	Christie Hospital NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose adjustment success	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.	Day 5 of treatment	No
Secondary	Mortality of patients	To examine the mortality of patients receiving individualised voriconazole dosing	35 Day after starting treatment	Yes
Secondary	Toxicity	To evaluate the adverse events that are attributable to voriconazole as assessed by CTCAE v4.	Day 5 of treatment and 35 day follow-up	Yes

External Links

•   Christie NHS website