Immunocompromised PatientPhase 2PIVOTALNCT01887457
Individualisation of Voriconazole Antifungal Therapy Antifungal Therapy
A Phase 2 study testing VFEND in people with Immunocompromised Patient and Aspergillosis, run by Brynn Chappell at 1 site in United Kingdom.
Trial summary
This is a trial to determine whether giving a patient a tailored dose of voriconazole is safe and effective. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immunocompromised Patient, Aspergillosis, Fusarium
- What is being tested?
- VFEND
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2014to Dec 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The Christie NHS Foundation Trust
Manchester, M20 4BX
About this study
Official title: PIVOTAL: Pharmacological Individualisation of VOriconazole Therapy for AntifungaL Treatment
This is a trial to determine whether giving a patient a tailored dose of voriconazole is safe and effective.
Read the 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
- Being tested
- VFEND
- Keywords
- voriconazole, VFEND, individualised, personalised
- Medical subject headings
- Aspergillosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VFENDDrug
Also called voriconazole
voriconazole will be administered in iv form
| Study group | Role | What they receive |
|---|---|---|
| Voriconazole | Experimental | 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. Receives: Drug: VFEND |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 5 of treatment
Secondary outcomes (2)
Mortality of patients
To examine the mortality of patients receiving individualised voriconazole dosing
Measured: 35 Day after starting treatment
Toxicity
To evaluate the adverse events that are attributable to voriconazole as assessed by CTCAE v4.
Measured: Day 5 of treatment and 35 day follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2013 (estimated)
- Study startSep 2014
- Primary completionNov 2016 (estimated)
- Study completionDec 2016 (estimated)
Why it stopped: Transfer of management of study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immunocompromised PatientStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brynn Chappell
- Sponsor type
- University, hospital or other
- Collaborators
- The Christie NHS Foundation Trust
- Responsible party
- Sponsor-investigator, Brynn Chappell, The Christie NHS Foundation Trust
- Investigators
- William Hope, Study chair, University of Liverpool
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01887457
- Sponsor's protocol ID
- 13_DOG06_172
- Other IDs
- 2013-002578-34
- Acronym
- PIVOTAL
- Status last verified
- Oct 2015
- First submitted
- 7 Jun 2013
- Last updated
- 7 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PIVOTAL: Pharmacological Individualisation of VOriconazole Therapy for AntifungaL Treatment
- ClinicalTrials.gov ID
- NCT01887457
- Acronym / sponsor ID
- PIVOTAL / 13_DOG06_172
- Conditions
- Immunocompromised Patient, Aspergillosis, Fusarium
- Keywords
- voriconazole, VFEND, individualised, personalised
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Transfer of management of study
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Brynn ChappellUniversity, hospital or other
- Collaborators
- The Christie NHS Foundation Trust
- Study start
- Sep 2014
- Primary completion
- Nov 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 26 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Voriconazole | Experimental | Drug: VFENDStandard 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VFENDAlso: voriconazolevoriconazole will be administered in iv form | Drug | Voriconazole |
Primary outcome
Dose adjustment success
Time frame: Day 5 of treatment
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.
2 secondary outcomes
Mortality of patients
Time frame: 35 Day after starting treatment
Toxicity
Time frame: Day 5 of treatment and 35 day follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2015.
- Christie NHS websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Hope study chair
University of Liverpool
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VFEND in people with Immunocompromised Patient and Aspergillosis, run by Brynn Chappell at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 7 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose adjustment success (time frame: Day 5 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2015.