AspergillosisPhase 1NCT00005912
Voriconazole to Prevent Systemic Fungal Infections in Children
A Phase 1 study testing Voriconazole in people with Aspergillosis and Candidiasis, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study will examine how children's bodies metabolize and eliminate the anti-fungal drug voriconazole. The results will yield information needed to make recommendations for safe and effective dosing of the drug in children. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Aspergillosis, Candidiasis, Fungal Diseases
- What is being tested?
- Voriconazole
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2000to Jan 2001
- Phase
- Phase 1
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Children (male or female) ages 2-12 years who require treatment for the prevention of systemic fungal infection.
Children who are expected to develop neutropenia lasting for more than 10 days following chemotherapy for one of the following conditions: leukemia, lymphoma, aplastic anemia, or as the preparative regimen for bone marrow transplantation.
Patients who are anticipated to live more than 3 months.
Females of child-bearing potential (post-menarchal) must have a negative pregnancy test at entry.
Informed consent of the parent or legally authorized representative obtained prior to entry.
Assent will be obtained from minors capable of understanding.
No patients who are receiving and cannot discontinue the following drugs at least 24 hours prior to study start: terfenadine and cisapride (due to the possibility of QTc prolongation). Omegprazole (an inhibitor of CYP2C19) which is known to increase plasma voriconazole levels.
No patients who have received the following drugs within 14 days prior to study entry: rifampicin, rifabutin, carbamazepine, phenytoin, nevirapine and barbiturates as these are potent inducers of hepatic enzymes and will result in undetectable levels of voriconazole.
No patients who have received astemizole within the previous 60 days.
No patients who are taking or are likely to receive any investigational drugs except: used for cancer treatment, antiretroviral agents, and drugs used for treatments of any AIDS defining opportunistic infections.
No patients with a history or hypersensitivity to or severe intolerance of azole antifungal agents.
No patients who have already been entered onto this protocol once.
No patient with medical history or evidence of cardiac arrhythmia.
No patients with AST and ALT greater than or equal to 5XULN.
No patients with moderate and severe renal impairment (i.e., calculated creatine clearance less than 30ml/min). If creatinine clearance is reduced to less than 30 ml/min at any time during the study, the patient must be discontinued from the study. Creatine clearance will be calculated using the following equation: 0.55 X height (cm)/serum creatinine (mg/dL).
Any other condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Official title: An Open Intravenous Multiple Dose, Multi-Center Study to Investigate the Pharmacokinetics, Safety and Toleration of Voriconazole in Children Aged 2-12 Years Who Require Treatment for the Prevention of Systemic Fungal Infection
This study will examine how children's bodies metabolize and eliminate the anti-fungal drug voriconazole. The results will yield information needed to make recommendations for safe and effective dosing of the drug in children. Children with reduced immune function-such as those receiving drugs for cancer treatment-are at high risk for serious fungal infections.
Children between 2 and 12 years old who need treatment to prevent fungal infections may be eligible for this study. Candidates will be screened with a physical examination, eye examination, and blood and urine tests.
Read more
Children in the study will be hospitalized for 21 days. They will receive voriconazole twice a day (every 12 hours) for 8 days, infused through a vein over a period of 1 to 2 hours. The dose will be determined based on the individual child's weight. Blood samples will be collected at various intervals before and after the infusions on days 1, 2, 4 and 8 to determine the amount of drug in the blood. On day 8, the child will have another physical and eye examination, as well as additional blood and urine tests. If additional treatment is required, voriconazole may be continued for up to day 21. (Children who require the drug for more than 21 days may receive it under another research protocol.) On the last day of treatment, the child will have another physical examination, and blood and urine tests. These procedures will be repeated again at 30 to 35 days following the last dose of drug. A small sample of blood will also be analyzed for genetic information related to the rate of metabolism of voriconazole-that is, how fast or slow it is cleared (eliminated) by the liver.
Voriconazole is effective against several different fungi. It may protect children against serious fungal infections with fewer side effects than standard available therapy.
Read the detailed description
The objective of this study is to evaluate the serum levels and pharmacokinetic parameters achieved following two dosage levels of voriconazole. In addition, the safety and toleration of intravenous voriconazole at two dosage levels in an immunocompromised pediatric patient population will be evaluated. Also, the plasma concentrations of the major metabolite of voriconazole (N-oxide) in these patients will be performed. The study is designed as a multi-center, open label multi-dose study of intravenous voriconazole. Intravenous voriconazole will be administered prophylactically twice daily to immunocompromised children at high risk for invasive mycoses. The patient population consists of children ages 2 years to 12 years of age; two age groups will be studied (2-<6, 6-12). Initial dosage levels will be 3mg/kg q12h and 4mg/kg q12h. The planned sample size is 24 children. For those children who do not complete the full 8 days of kinetics, a replacement patient will be added. Immunocompromised children at high risk for invasive mycoses will receive voriconazole prophylactically. Therapy will be initiated within 48 hours after completion of chemotherapy. Voriconazole therapy will continue until recovery from neutropenia. The first 12 children will initially receive a loading dose of 6mg/kg X 2 doses followed by 3mg/kg BID through day 4 of therapy. Twelve hour pharmacokinetics will be collected on day 4. Children will then receive 4mg/kg starting on the second dose of day 4 and will continue at that dosage level until recovery from neutropenia. Kinetics will again be collected at the 4mg/kg dosage level on day 8 of therapy. If the mean peak plasma concentration of voriconazole in the first 12 patients following 4mg/kg q12h dosing is less than 4,000ng/ml., the remaining 12 patients will receive voriconazole after day 4 at a dosage of 5mg/kg.
- Conditions
- Aspergillosis, Candidiasis, Fungal Diseases, Mycoses
- Being tested
- Voriconazole
- Keywords
- Aspergillosis, Candidiasis, Fungal Infections, Fungemia, Prophylactic Antifungal Therapy, Pediatric Fungal Infection
- Medical subject headings
- Aspergillosis, Candidiasis, Mycoses, Fungemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VoriconazoleDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startJun 2000
- Study completionJan 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for AspergillosisStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 1
- Primary purpose
- Treatment
- Enrolment
- 48 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005912
- Sponsor's protocol ID
- 000150
- Other IDs
- 00-C-0150
- Status last verified
- Jun 2000
- First submitted
- 14 Jun 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Walsh TJ, Hiemenz JW, Anaissie E. Recent progress and current problems in treatment of invasive fungal infections in neutropenic patients. Infect Dis Clin North Am. 1996 Jun;10(2):365-400. doi: 10.1016/s0891-5520(05)70303-2.
PubMed 8803625Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med. 1982 Jan;72(1):101-11. doi: 10.1016/0002-9343(82)90594-0. No abstract available.
PubMed 7058815Walsh TJ, Gonzalez C, Lyman CA, Chanock SJ, Pizzo PA. Invasive fungal infections in children: recent advances in diagnosis and treatment. Adv Pediatr Infect Dis. 1996;11:187-290. No abstract available.
PubMed 8718464
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Intravenous Multiple Dose, Multi-Center Study to Investigate the Pharmacokinetics, Safety and Toleration of Voriconazole in Children Aged 2-12 Years Who Require Treatment for the Prevention of Systemic Fungal Infection
- ClinicalTrials.gov ID
- NCT00005912
- Acronym / sponsor ID
- 000150
- Conditions
- Aspergillosis, Candidiasis, Fungal Diseases, Mycoses
- Keywords
- Aspergillosis, Candidiasis, Fungal Infections, Fungemia, Prophylactic Antifungal Therapy, Pediatric Fungal Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2000
- Study completion
- Jan 2001
- First posted
- 10 Dec 2002 (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 study will examine how children's bodies metabolize and eliminate the anti-fungal drug voriconazole. The results will yield information needed to make recommendations for safe and effective dosing of the drug in children. Children with reduced immune function-such as those receiving drugs for cancer treatment-are at high risk for serious fungal infections.
Children between 2 and 12 years old who need treatment to prevent fungal infections may be eligible for this study. Candidates will be screened with a physical examination, eye examination, and blood and urine tests.
Children in the study will be hospitalized for 21 days. They will receive voriconazole twice a day (every 12 hours) for 8 days, infused through a vein over a period of 1 to 2 hours. The dose will be determined based on the individual child's weight. Blood samples will be collected at various intervals before and after the infusions on days 1, 2, 4 and 8 to determine the amount of drug in the blood. On day 8, the child will have another physical and eye examination, as well as additional blood and urine tests. If additional treatment is required, voriconazole may be continued for up to day 21. (Children who require the drug for more than 21 days may receive it under another research protocol.) On the last day of treatment, the child will have another physical examination, and blood and urine tests. These procedures will be repeated again at 30 to 35 days following the last dose of drug. A small sample of blood will also be analyzed for genetic information related to the rate of metabolism of voriconazole-that is, how fast or slow it is cleared (eliminated) by the liver.
Voriconazole is effective against several different fungi. It may protect children against serious fungal infections with fewer side effects than standard available therapy.
Detailed description
The objective of this study is to evaluate the serum levels and pharmacokinetic parameters achieved following two dosage levels of voriconazole. In addition, the safety and toleration of intravenous voriconazole at two dosage levels in an immunocompromised pediatric patient population will be evaluated. Also, the plasma concentrations of the major metabolite of voriconazole (N-oxide) in these patients will be performed. The study is designed as a multi-center, open label multi-dose study of intravenous voriconazole. Intravenous voriconazole will be administered prophylactically twice daily to immunocompromised children at high risk for invasive mycoses. The patient population consists of children ages 2 years to 12 years of age; two age groups will be studied (2-<6, 6-12). Initial dosage levels will be 3mg/kg q12h and 4mg/kg q12h. The planned sample size is 24 children. For those children who do not complete the full 8 days of kinetics, a replacement patient will be added. Immunocompromised children at high risk for invasive mycoses will receive voriconazole prophylactically. Therapy will be initiated within 48 hours after completion of chemotherapy. Voriconazole therapy will continue until recovery from neutropenia. The first 12 children will initially receive a loading dose of 6mg/kg X 2 doses followed by 3mg/kg BID through day 4 of therapy. Twelve hour pharmacokinetics will be collected on day 4. Children will then receive 4mg/kg starting on the second dose of day 4 and will continue at that dosage level until recovery from neutropenia. Kinetics will again be collected at the 4mg/kg dosage level on day 8 of therapy. If the mean peak plasma concentration of voriconazole in the first 12 patients following 4mg/kg q12h dosing is less than 4,000ng/ml., the remaining 12 patients will receive voriconazole after day 4 at a dosage of 5mg/kg.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| Voriconazole | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 8803625Walsh TJ, Hiemenz JW, Anaissie E. Recent progress and current problems in treatment of invasive fungal infections in neutropenic patients. Infect Dis Clin North Am. 1996 Jun;10(2):365-400. doi: 10.1016/s0891-5520(05)70303-2.
- Background: PubMed 7058815Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med. 1982 Jan;72(1):101-11. doi: 10.1016/0002-9343(82)90594-0. No abstract available.
- Background: PubMed 8718464Walsh TJ, Gonzalez C, Lyman CA, Chanock SJ, Pizzo PA. Invasive fungal infections in children: recent advances in diagnosis and treatment. Adv Pediatr Infect Dis. 1996;11:187-290. No abstract available.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Voriconazole in people with Aspergillosis and Candidiasis, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. 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 States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005912, which also lists 3 linked publications.
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 4 Mar 2008.