LeukopeniaPhase 3NCT00811928
Safety and Efficacy Study of Posaconazole vs. Fluconazole for Prevention of Invasive Fungal Infection (P05387 AM1)(COMPLETED)
A Phase 3 study testing Posaconazole and Fluconazole in people with Leukopenia, run by Merck Sharp & Dohme LLC.
Trial summary
A randomized, open label parallel controlled, multicenter study to evaluate safety and efficacy of Posaconazole oral suspension vs Fluconazole (capsule) in high-risk leukopenic patients for prevention of invasive fungal infection Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukopenia
- What is being tested?
- Posaconazole and Fluconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 252 participants
- Where
- No sites listed yet
- Study dates
- Nov 2008to May 2010
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must be 18-70 years of age of either sex
- Persistent neutropenia (Absolute Neutrophil Count [ANC] < 500/mm^3 [0.5x10^9/L]）or probable neutropenia in 3-5 days is anticipated. Neutropenia >= 7 days caused by the following reasons
- Standard or dose-intense chemotherapy, anthracyclines or other acceptable chemotherapies ( any investigational drug is not permitted) for Acute Myelogenous Leukemia (AML) treatment
- Retreatment of chemotherapy in case of AML recurrence
- Myelodysplastic syndrome (MDS) shifts to AML and bone marrow arrest induction chemotherapy is required (not including acute phase of chronic myelogenous leukemia [CML])
- Informed consent obtained from participant or legal guardian
Who cannot join
- Participants previously treated with amphotericin B (AMB), fluconazole (FLZ), or itraconazole (ITZ) within 30 days of enrollment.
- Participants who have taken the following drugs:
- terfenadine, cisapride, and ebastine within 24 hours before entry
- astemizole at entry or within 10 days before entry
- cimetidine, rifampin, carbamazepine, phenytoin, rifabutin, barbiturates, isoniazid atharanthine and anthracyclines within 24 hours before entry
- The above drugs are refrained during the investigation
Show all 18Show fewer
- Serious organ diseases except hematological disorder such as cardiac or neurologic disorders or impairment expected to be unstable or progressive during the course of this study (eg, seizures or demyelinating syndromes, acute myocardial infarction within 3 months of study entry, myocardial ischemia, congestive heart failure, atrial fibrillation with ventricular rate <60/min, or history of torsades de pointes, symptomatic ventricular or sustained arrhythmias), unstable electrolyte abnormalities.
- Participants who have used any investigational drugs or biologic agents other than their chemotherapy regimens within 30 days of study entry.
- Prior enrollment in this study.
- Participants with known or suspected hypersensitivity or idiosyncratic reaction to azole agents or amphotericin B.
- Participants with known or suspected invasive fungal infection (IFI) at screen
- Participants with severe renal insufficiency (estimated creatinine clearance less than 50 mL/minute or likely to require dialysis during the study), Alanine transaminase (ALT), Aspartate transaminase (AST), alkaline phosphatase or total bilirubin are >2× (Upper Limit of Normal) ULN.
- Participants having an electrocardiogram (ECG) with a prolonged QTc interval: QTc greater than 450 msec for men and greater than 470 msec for women.
- Participants with AML or CML history.
- Participants with a history of allogeneic hematopoietic stem cell, bone marrow transplantation, autologous stem cell transplantation history.
- Female participants who are pregnant or are nursing.
- Alcohol and/or drug abuse.
- Participants cannot be compliant in the opinion of the investigator.
About this study
Official title: A Randomized, Open Label Parallel Controlled, Multicenter Study to Evaluate Safety and Efficacy of Posaconazole Oral Suspension Vs. Fluconazole (Capsule) in High-risk Leukopenic Patients for Prevention of Invasive Fungal Infection
A randomized, open label parallel controlled, multicenter study to evaluate safety and efficacy of Posaconazole oral suspension vs Fluconazole (capsule) in high-risk leukopenic patients for prevention of invasive fungal infection
- Conditions
- Leukopenia
- Being tested
- Posaconazole, Fluconazole
- Keywords
- high-risk leukopenic patients
- Medical subject headings
- Leukopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PosaconazoleDrug
Also called Noxafil, SCH 056592
40 mg/mL; 200 mg (5 mL) TID
Treatment was continued with each cycle of chemotherapy until:
- The onset of a proven or probable diagnosis of invasive fungal infection (IFI)
- 3 chemotherapy cycles or
- Total treatment duration up to 12 weeks (84 days)
FluconazoleDrug
50 mg/capsule (2 capsules), 150 mg/capsule (2 capsules);
400 mg QD
Treatment was continued with each cycle of chemotherapy until:
- The onset of a proven or probable diagnosis of invasive fungal infection (IFI)
- 3 chemotherapy cycles or
- Total treatment duration up to 12 weeks (84 days)
| Study group | Role | What they receive |
|---|---|---|
| Posaconazole | Active comparator | Posaconazole oral suspension 200 mg three times a day (TID) Receives: Drug: Posaconazole |
| Fluconazole | Active comparator | Fluconazole 400 mg once daily (QD) Receives: Drug: Fluconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Proven or Probable Diagnosis of Invasive Fungal Infection (IFI) During the Treatment Period
Number of participants developing a proven or probable IFI from randomization to the last dosage date (up to 12 weeks [84 days]) plus 7 days. IFI diagnosis criteria may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, microbiological criteria with corresponding clinical signs and symptoms.
Measured: Up to 12 Weeks (84 days) plus 7 days
Secondary outcomes (6)
Number of Participants With Proven or Probable Diagnosis of IFI Within 100 Days From Randomization
Number of participants who developed a proven or probable IFI from randomization date to Day 100 of follow-up visit. IFI diagnosis criteria may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, microbiological criteria with corresponding clinical signs and symptoms.
Measured: From randomization date to Day 100
Time From Randomization to the First Onset of Proven or Probable IFI
The time measured in days to the first occurrence of proven/probable IFI diagnosis in the entire FAS population from randomization to Day 100 of follow-up visit. Participants may not have accepted immediate antifungal treatment and later received antifungal treatment based upon further investigator review of the participant's IFI condition. IFI diagnosis criteria may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, positive blood/biopsy cultures with corresponding clinical signs and symptoms.
Measured: From randomization date to Day 100
Time From Randomization to Administration of First Systemic Antifungal Intravenous (IV) Therapy
The time measured in days from randomization to the administration of the first concomitant systemic anti-fungal therapy in the entire FAS population. Not all participants who accepted systemic anti-fungal therapy may have had a IFI clinical diagnosis. IFI diagnosis criteria for antifungal therapy administration may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, microbiological criteria with corresponding clinical signs and symptoms.
Measured: Up to 12 weeks (84 days)
Number of Participants With Clinical Failure During Treatment
Clinical failure was defined as follows:
- Presence of a proven or probable IFI
- Systemic antifungal treatment (IV) for 4 consecutive days or more than 10 days total
- Discontinuation due to adverse event (AE) possibly or probably related to study drug
- Lost-to-follow-up or discontinuation from the study for any reason with loss to follow-up during the Treatment Phase
Measured: Up to 12 weeks (84 days)
Number of Participants in Whom All-cause Mortality Occurred Within 100 Days From Randomization
Death from any cause.
Measured: Randomization date to Day 100
Number of Participants in Whom Mortality is Unlikely, Possibly, and Probably Related to Fungal Infection Occurred Within 100 Days From Randomization
Exact Causes of Death and Their Relationship to IFI Episode Were As Follows:
- Unlikely related: participant completed treatment and cause of death was due to primary disease or complication
- Possibly related: IFI undergoing treatment without stabilization, or with failure to have a complete remission, where cause of death might have been due to IFI, including progression or relapse of primary disease
- Probably related: autopsy or clinical signs suggested that progression of IFI was the probable cause of death
Measured: From randomization date to Day 100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2008 (estimated)
- Study startNov 2008
- Primary completionMay 2010
- Study completionMay 2010
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukopeniaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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
- 252 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00811928
- Sponsor's protocol ID
- P05387
- Status last verified
- Mar 2017
- First submitted
- 18 Dec 2008
- Last updated
- 7 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php
Publications
Shen Y, Huang XJ, Wang JX, Jin J, Hu JD, Yu K, Wu DP, Wang SJ, Yu L, Chen XQ, Liu T, Liang YM, Chen FP, Li Y, Shen ZX. Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study. Int J Clin Pharmacol Ther. 2013 Sep;51(9):738-45. doi: 10.5414/CP201880.
PubMed 23924680
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open Label Parallel Controlled, Multicenter Study to Evaluate Safety and Efficacy of Posaconazole Oral Suspension Vs. Fluconazole (Capsule) in High-risk Leukopenic Patients for Prevention of Invasive Fungal Infection
- ClinicalTrials.gov ID
- NCT00811928
- Acronym / sponsor ID
- P05387
- Conditions
- Leukopenia
- Keywords
- high-risk leukopenic patients
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 252 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Nov 2008
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 19 Dec 2008 (estimated)
- Results
- Posted 13 Sep 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, open label parallel controlled, multicenter study to evaluate safety and efficacy of Posaconazole oral suspension vs Fluconazole (capsule) in high-risk leukopenic patients for prevention of invasive fungal infection
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Posaconazole | Active comparator | Drug: PosaconazolePosaconazole oral suspension 200 mg three times a day (TID) |
| Fluconazole | Active comparator | Drug: FluconazoleFluconazole 400 mg once daily (QD) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Participants must be 18-70 years of age of either sex
- Persistent neutropenia (Absolute Neutrophil Count [ANC] < 500/mm^3 [0.5x10^9/L]）or probable neutropenia in 3-5 days is anticipated. Neutropenia >= 7 days caused by the following reasons
- Informed consent obtained from participant or legal guardian
Key exclusion criteria (18 listed)
- Participants previously treated with amphotericin B (AMB), fluconazole (FLZ), or itraconazole (ITZ) within 30 days of enrollment.
- Participants who have taken the following drugs:
- The above drugs are refrained during the investigation
- Serious organ diseases except hematological disorder such as cardiac or neurologic disorders or impairment expected to be unstable or progressive during the course of this study (eg, seizures or demyelinating syndromes, acute myocardial infarction within 3 months of study entry, myocardial ischemia, congestive heart failure, atrial fibrillation with ventricular rate <60/min, or history of torsades de pointes, symptomatic ventricular or sustained arrhythmias), unstable electrolyte abnormalities.
- Participants who have used any investigational drugs or biologic agents other than their chemotherapy regimens within 30 days of study entry.
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 |
|---|---|---|
| PosaconazoleAlso: Noxafil, SCH 05659240 mg/mL; 200 mg (5 mL) TID Treatment was continued with each cycle of chemotherapy until: * The onset of a proven or probable diagnosis of invasive fungal infection (IFI) * 3 chemotherapy cycles or * Total treatment duration up to 12 weeks (84 days) | Drug | Posaconazole |
| Fluconazole50 mg/capsule (2 capsules), 150 mg/capsule (2 capsules); 400 mg QD Treatment was continued with each cycle of chemotherapy until: * The onset of a proven or probable diagnosis of invasive fungal infection (IFI) * 3 chemotherapy cycles or * Total treatment duration up to 12 weeks (84 days) | Drug | Fluconazole |
Primary outcome
Number of Participants With Proven or Probable Diagnosis of Invasive Fungal Infection (IFI) During the Treatment Period
Time frame: Up to 12 Weeks (84 days) plus 7 days
Number of participants developing a proven or probable IFI from randomization to the last dosage date (up to 12 weeks [84 days]) plus 7 days. IFI diagnosis criteria may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, microbiological criteria with corresponding clinical signs and symptoms.
6 secondary outcomes
Number of Participants With Proven or Probable Diagnosis of IFI Within 100 Days From Randomization
Time frame: From randomization date to Day 100
Time From Randomization to the First Onset of Proven or Probable IFI
Time frame: From randomization date to Day 100
Time From Randomization to Administration of First Systemic Antifungal Intravenous (IV) Therapy
Time frame: Up to 12 weeks (84 days)
Number of Participants With Clinical Failure During Treatment
Time frame: Up to 12 weeks (84 days)
Number of Participants in Whom All-cause Mortality Occurred Within 100 Days From Randomization
Time frame: Randomization date to Day 100
Number of Participants in Whom Mortality is Unlikely, Possibly, and Probably Related to Fungal Infection Occurred Within 100 Days From Randomization
Time frame: From randomization date to Day 100
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23924680Shen Y, Huang XJ, Wang JX, Jin J, Hu JD, Yu K, Wu DP, Wang SJ, Yu L, Chen XQ, Liu T, Liang YM, Chen FP, Li Y, Shen ZX. Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study. Int J Clin Pharmacol Ther. 2013 Sep;51(9):738-45. doi: 10.5414/CP201880.
- Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Posaconazole and Fluconazole in people with Leukopenia, run by Merck Sharp & Dohme LLC.
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 6 inclusion and 18 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 7 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
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 13 Sep 2011). 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?
Number of Participants With Proven or Probable Diagnosis of Invasive Fungal Infection (IFI) During the Treatment Period (time frame: Up to 12 Weeks (84 days) plus 7 days). 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 NCT00811928, which also lists 1 linked publication.
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 Apr 2017.