Antifungal Prophylaxis of Invasive Fungal InfectionsPhase 3IMPROVITNCT00289991

Voriconazole Versus Itraconazole In Primary Prophylaxis Of Invasive Fungal Infection (IFI) In Subjects With Allogeneic Hematopoietic Stem Cell Transplants (HSCT)

A Phase 3 study testing Itraconazole and Vfend - voriconazole in people with Antifungal Prophylaxis of Invasive Fungal Infections, run by Pfizer at 49 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Study is to compare antifungal prophylaxis of Voriconazole and Itraconazole in subjects who have had a Stem Cell Transplant. The success of the end point will be measured using evidence of Infection, drug compliance and survival. Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: Antifungal Prophylaxis of Invasive Fungal Infections
What is being tested?: Itraconazole and Vfend - voriconazole
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 489 participants
Where: 49 sitesin 12 countries
Study dates: Mar 2006to Feb 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Allogeneic HSCT for acute leukemia (AML, ALL or myelodysplastic syndrome) failed lymphoma therapy or transformation of CML
Male and Female over 12 years or greater

Who cannot join

Possible, probable or proven IFI at study entry or at any time in 6 months prior to study entry, defined according to the 'consensus criteria' (Ascioglu et al 2002)
Previous history of zygomycosis
Anticipated survival less than one month

Trial locations and contacts

49 sites in 12 countries.

Country

City, postcode or hospital

49 sites in 12 countries

United Kingdom12 sites

Pfizer Investigational Site
Bristol, BS2 8BL
Pfizer Investigational Site
Cambridge, CB2 2QQ
Pfizer Investigational Site
Cardiff, CF14 4XW
Pfizer Investigational Site
Glasgow, G12 0YN
Pfizer Investigational Site
Glasgow, G4 0SF
Pfizer Investigational Site
Leeds, LS9-7TF
Pfizer Investigational Site
Leicester, LW1 5WW
Pfizer Investigational Site
London, Nw3 2qg
Pfizer Investigational Site
London, SE1 9RT
Pfizer Investigational Site
London, SE5 9RS
Pfizer Investigational Site
Manchester, M20 4BX
Pfizer Investigational Site
Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Spain10 sites

Pfizer Investigational Site
Badalona, Barcelona, 08916
Pfizer Investigational Site
Barcelona, Barcelona, 08025
Pfizer Investigational Site
Barcelona, Barcelona, 08036
Pfizer Investigational Site
Madrid, Madrid, 28006
Pfizer Investigational Site
Madrid, Madrid, 28034
Pfizer Investigational Site
Madrid, Madrid, 28041
Pfizer Investigational Site
Salamanca, Salamanca, 37007
Pfizer Investigational Site
Seville, Sevilla, 41013
Pfizer Investigational Site
Valencia, Valencia, 46009
Pfizer Investigational Site
Valencia, Valencia, 46010

Other trials in Spain

France8 sites

Pfizer Investigational Site
Caen, 14033
Pfizer Investigational Site
Créteil, 94010
Pfizer Investigational Site
Marseille, Cedex 09, 13273
Pfizer Investigational Site
Paris, 75475
Pfizer Investigational Site
Pessac, 33600
Pfizer Investigational Site
Rouen, 76038
Pfizer Investigational Site
Vandœuvre-lès-Nancy, 54511
Pfizer Investigational Site
Villejuif, 94805

Other trials in France

Canada5 sites

Pfizer Investigational Site
Hamilton, Ontario, L8N 3Z5
Pfizer Investigational Site
Montreal, Quebec, H1T 2M4
Pfizer Investigational Site
Vancouver, British Columbia, V5Z 1M9
Pfizer Investigational Site
Winnipeg, Manitoba, R3A 1R9
Pfizer Investigational Site
Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Czechia2 sites

Pfizer Investigational Site
Bmo, 625 00
Pfizer Investigational Site
Prague, 128 20

Other trials in Czechia

Greece2 sites

Pfizer Investigational Site
Athens, 11527
Pfizer Investigational Site
Exohi Asvestohoriou, Thessaloniki, 57010

Other trials in Greece

Portugal2 sites

Pfizer Investigational Site
Lisbon, 1099-023
Pfizer Investigational Site
Porto, 4200-072

Other trials in Portugal

Russia2 sites

Pfizer Investigational Site
Moscow, 117997
Pfizer Investigational Site
Saint Petersburg, 197089

Other trials in Russia

Switzerland2 sites

Pfizer Investigational Site
Ch-4031 Basel
Pfizer Investigational Site
Geneva, CH-1211

Other trials in Switzerland

Turkey (Türkiye)2 sites

Pfizer Investigational Site
Ankara, 06590
Pfizer Investigational Site
Kayseri, 38039

Other trials in Turkey (Türkiye)

Egypt1 site

Pfizer Investigational Site
Cairo

Other trials in Egypt

Jordan1 site

Pfizer Investigational Site
Amman

Other trials in Jordan

About this study

Official title: Prospective, Open-Label, Comparative, Multi-Center Study Of Voriconazole Compared To Itraconazole For The Primary Prophylaxis Of Invasive Fungal Infection (IFI) With Allogeneic Hematopoietic Stem Cell Transplants (HSCT)

Conditions: Antifungal Prophylaxis of Invasive Fungal Infections
Being tested: Itraconazole, Vfend - voriconazole

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ItraconazoleDrug
Prophylaxis
Vfend - voriconazoleDrug
Also called Vfend
Prophylaxis

Study groups in NCT00289991
Study group	Role	What they receive
Itraconazole	Active comparator	Not described Receives: Drug: Itraconazole
Voriconazole	Experimental	Not described Receives: Drug: Vfend - voriconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Success at Day 180: Percent of Responders (Randomization Strata)
Percent of responders (by randomization strata) with success of antifungal prophylaxis at 180 days after allogeneic hematopoietic stem cell transplant (HSCT). Success: alive at Day 180 (Visit 9), had not developed a breakthrough proven or probable invasive fungal infection (IFI) by Visit 9, and received full course of study drug prophylaxis without interruption of greater than 14 days in total during the prophylaxis period; defined as failure if these criteria were not met. Additionally, if subject withdrew from study completely before Visit 9, imputed as failure at Visit 9 (programmatically).
Measured: Day 180 (Visit 9)

Secondary outcomes (8)

Success at Day 100: Percent of Responders (Randomization Strata)
Percent of responders (by randomization strata) with success of antifungal prophylaxis at 100 days after allogeneic HSCT. Success defined as: alive at Day 100 (Visit 7), had not developed a breakthrough proven or probable IFI by Visit 7, and received full course of study drug prophylaxis without an interruption of >14 days in total during the prophylaxis period; defined as failure if these criteria were not met. Additionally, if subject withdrew from study completely before Visit 7, imputed as failure at Visit 7 (programmatically).
Measured: Day 100 (Visit 7)
Time to Breakthrough Invasive Fungal Infection (IFI)
Summary of time (in days) from start of prophylaxis to first recorded occurrence of breakthrough proven or probable IFI.
Measured: Day 1 up to Day 180 (Visit 9)
Percent of Subjects With Occurrence of Breakthrough IFI
Percent of subjects with occurrence of breakthrough IFI (proven or probable). Included all subjects in the MITT population.
Measured: Day 1 up to Day 100 (Visit 7) and Day 180 (Visit 9)
Survival: Percent of Subjects Who Died at or Before Day 180
Percent of subjects who died at or before Day 180, derived from the crude death rate. All subjects in the MITT population included in this proportion.
Measured: Day 1 up to Day 180 (Visit 9)
Time to Discontinuation of Study Treatment
Time in days to discontinuation of study treatment defined as the number of days from first dose to last dose inclusive as recorded in the dosing log.
Measured: Day 1 up to Day 180 (Visit 9)
Survival: Percent of Subjects Who Died Within 1 Year
Percent of subjects who died within 1 year after transplant, derived from the crude death rate. All subjects in the MITT population included in this proportion. Only deaths up until and including 365 days after first dose of study medication included in the analysis.
Measured: Day 1 up to 1 year (Day 365)
Duration of Treatment
Median duration in days of treatment. Treatment is defined as the total number of days on which subjects took medication.
Measured: Day 1 up to Day 180
Percent of Subjects With Use of Other Systemic Antifungal Agents as Empirical or Therapeutic Treatment
Percent of subjects who used other systemic antifungal agents as empirical or therapeutic treatment, defined as either empirical: subject took a systemic antifungal agent at any time after the day of first dose of medication and did not develop a breakthrough proven or probable IFI during the study or therapeutic: subject developed a breakthrough proven or probable IFI.
Measured: Day 1 up to Day 180

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2006Feb 2009

First posted10 Feb 2006 (estimated)
Study startMar 2006
Primary completionFeb 2009
Study completionFeb 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Antifungal Prophylaxis of Invasive Fungal InfectionsStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
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 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 489 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00289991
Sponsor's protocol ID: A1501073
Acronym: IMPROVIT
Status last verified: Oct 2015
First submitted: 9 Feb 2006
Last updated: 20 Nov 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Low-Dose Liposomal Amphotericin B for Invasive Fungal Infection Prophylaxis in Neutropenic Children
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RecruitingObservational study
Liposomal Amphotericin B and Isavuconazole/Posaconazole in Br-IFD（ Breakthrough Invasive Fungal Disease） in Patients With Malignant Hematological Diseases
Invasive Fungal Disease

All Antifungal Prophylaxis of Invasive Fungal Infections trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Prospective, Open-Label, Comparative, Multi-Center Study Of Voriconazole Compared To Itraconazole For The Primary Prophylaxis Of Invasive Fungal Infection (IFI) With Allogeneic Hematopoietic Stem Cell Transplants (HSCT)
ClinicalTrials.gov ID: NCT00289991
Acronym / sponsor ID: IMPROVIT / A1501073
Conditions: Antifungal Prophylaxis of Invasive Fungal Infections
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 489 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: Mar 2006
Primary completion: Feb 2009 (actual)
Study completion: Feb 2009 (actual)
First posted: 10 Feb 2006 (estimated)
Results: Posted 10 Mar 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Itraconazole	Active comparator	Drug: Itraconazole
Voriconazole	Experimental	Drug: Vfend - voriconazole

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (2 listed)

Allogeneic HSCT for acute leukemia (AML, ALL or myelodysplastic syndrome) failed lymphoma therapy or transformation of CML
Male and Female over 12 years or greater

Key exclusion criteria (3 listed)

Possible, probable or proven IFI at study entry or at any time in 6 months prior to study entry, defined according to the 'consensus criteria' (Ascioglu et al 2002)
Previous history of zygomycosis
Anticipated survival less than one month

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
ItraconazoleProphylaxis	Drug	Itraconazole
Vfend - voriconazoleAlso: VfendProphylaxis	Drug	Voriconazole

Primary outcome

Success at Day 180: Percent of Responders (Randomization Strata)
Time frame: Day 180 (Visit 9)
Percent of responders (by randomization strata) with success of antifungal prophylaxis at 180 days after allogeneic hematopoietic stem cell transplant (HSCT). Success: alive at Day 180 (Visit 9), had not developed a breakthrough proven or probable invasive fungal infection (IFI) by Visit 9, and received full course of study drug prophylaxis without interruption of greater than 14 days in total during the prophylaxis period; defined as failure if these criteria were not met. Additionally, if subject withdrew from study completely before Visit 9, imputed as failure at Visit 9 (programmatically).

8 secondary outcomes

Success at Day 100: Percent of Responders (Randomization Strata)
Time frame: Day 100 (Visit 7)
Time to Breakthrough Invasive Fungal Infection (IFI)
Time frame: Day 1 up to Day 180 (Visit 9)
Percent of Subjects With Occurrence of Breakthrough IFI
Time frame: Day 1 up to Day 100 (Visit 7) and Day 180 (Visit 9)
Survival: Percent of Subjects Who Died at or Before Day 180
Time frame: Day 1 up to Day 180 (Visit 9)
Time to Discontinuation of Study Treatment
Time frame: Day 1 up to Day 180 (Visit 9)
Survival: Percent of Subjects Who Died Within 1 Year
Time frame: Day 1 up to 1 year (Day 365)
Duration of Treatment
Time frame: Day 1 up to Day 180
Percent of Subjects With Use of Other Systemic Antifungal Agents as Empirical or Therapeutic Treatment
Time frame: Day 1 up to Day 180

Results and safety

Results posted to the registry on 10 Mar 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Voriconazole	234	176
Itraconazole	255	175

Primary outcome: Success at Day 180: Percent of Responders (Randomization Strata)

Time frame: Day 180 (Visit 9). Number. Unit: percent of participants

Measure	Voriconazole n = 224	Itraconazole n = 241
Myeloablative/matched related (n=66, 85)	59.1	44.7
Myeloablative/mismatched unrelated (n=59, 58)	52.5	25.9
Non-myeloablative/matched related (n=58, 57)	34.5	28.1
Non-myeloablative/mismatched unrelated (n=41, 41)	46.3	26.8

Voriconazole vs Itraconazole: percent difference adjusted proportions: 16.4 (95% CI 7.7 to 25.1), Difference in adjusted responder rates

Population analysed: Modified Intent to Treat (MITT): primary analysis population; all randomized subjects: received at least 1 dose of randomized study drug and had allogeneic HSCT; data from 1 site excluded due to Good Clinical Practice (GCP) deviations; (n)=number of subjects with analyzable data at observation for voriconazole and itraconazole, respectively.

8 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Voriconazole	111 of 234 (47.4%)	228 of 234 (97.4%)	Not reported
Itraconazole	95 of 255 (37.3%)	252 of 255 (98.8%)	Not reported

Limitations and caveats (from the sponsor): Data was excluded from 1 site due to Good Clinical Practices deviations.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.

Related trials for Antifungal Prophylaxis of Invasive Fungal Infections

RecruitingPhase 2
Phase 2 EL219 Versus Liposomal Amphotericin B or Voriconazole for Early Antifungal Therapy
Invasive Mould Infection
RecruitingObservational study
Low-dose Liposomal Amphotericin B for Antifungal Prophylaxis in Prolonged Neutropenia Patients
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia
RecruitingObservational study
Low-Dose Liposomal Amphotericin B for Invasive Fungal Infection Prophylaxis in Neutropenic Children
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RecruitingObservational study
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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.

Pfizer CT.gov Call Center study director

Pfizer

49 sites in 12 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Itraconazole and Vfend - voriconazole in people with Antifungal Prophylaxis of Invasive Fungal Infections, run by Pfizer at 49 sites in 12 countries.

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 2 inclusion and 3 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: finished, as of the sponsor's last update on 20 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United Kingdom, Spain, France, Canada, Czechia and 7 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Mar 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Success at Day 180: Percent of Responders (Randomization Strata) (time frame: Day 180 (Visit 9)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00289991.

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 20 Nov 2015.