Individualisation of Voriconazole Antifungal Therapy Antifungal Therapy (PIVOTAL)

This study has suspended participant recruitment.
(Transfer of management of study)
Sponsor:
Collaborator:
Christie Hospital NHS Foundation Trust
Information provided by (Responsible Party):
Colin Lunt, Christie Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01887457
First received: June 7, 2013
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Immunocompromised Patient
Aspergillosis
Fusarium
Drug: VFEND
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Christie Hospital NHS Foundation Trust:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 33
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)
Arms Assigned Interventions
Experimental: 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.
Drug: VFEND
voriconazole will be administered in iv form
Other Name: voriconazole

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01887457

Locations
United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Colin Lunt
Christie Hospital NHS Foundation Trust
Investigators
Study Chair: William Hope University of Liverpool
  More Information

Additional Information:
No publications provided

Responsible Party: Colin Lunt, Clinical Trials Project Manager, Christie Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01887457     History of Changes
Other Study ID Numbers: 13_DOG06_172, 2013-002578-34
Study First Received: June 7, 2013
Last Updated: June 16, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Christie Hospital NHS Foundation Trust:
voriconazole
VFEND
individualised
personalised

Additional relevant MeSH terms:
Aspergillosis
Hyalohyphomycosis
Dermatomycoses
Skin Diseases, Infectious
Infection
Mycoses
Skin Diseases
Antifungal Agents
Clotrimazole
Miconazole
Voriconazole
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Local
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014