Acquired Immunodeficiency SyndromePhase 3NCT00001646
Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
A Phase 3 study testing Voriconazole and Amphotericin B in people with Acquired Immunodeficiency Syndrome and Aspergillosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Invasive aspergillosis is a fungal disease which is increasing in incidence with the increase in immunocompromised persons in our population. Persons with prolonged neutropenia secondary to cytotoxic chemotherapies are at the highest risk for acute aspergillosis. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acquired Immunodeficiency Syndrome, Aspergillosis, HIV Infections
- What is being tested?
- Voriconazole and Amphotericin B
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 1997to Aug 2000
- Phase
- Phase 3
- 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
Males and females of greater than 12 years of age with any of the following conditions:
Allogeneic or autologous bone marrow/ peripheral stem cell transplant.
Hematological malignancy (including lymphoma).
Aplastic anemia and myelodysplastic syndromes (currently on immunosuppressive treatment).
Solid organ transplantation.
Solid organ malignancy (after cytotoxic chemotherapy).
HIV infection/AIDS.
High dose prolonged corticosteroid therapy (greater than or equal to 20 mg daily of prednisone or equivalent for greater than 3 weeks) or prolonged therapy with other immunosuppressive agents (e.g., azathioprine, methotrexate).
WITH a diagnosis of definite or probable acute invasive aspergillosis.
The fungal infection at baseline should represent a new episode of acute invasive aspergillosis. Any course of systemic treatment with amphotericin B (conventional or lipid formulation) or itraconazole should have been completed at least 8 weeks prior to study entry.
Signed informed consent must be obtained prior to study participation (patient, relative or legal representative). For patients aged 12-17 years, the written informed consent of the parents or legal guardian must also be obtained.
Women of child bearing potential must have a negative pregnancy test at entry and must agree to use barrier methods of contraception throughout the study.
No patients with sarcoidosis, aspergilloma or allergic bronchopulmonary aspergillosis.
No patients with chronic invasive aspergillosis with a duration of symptoms or radiological findings for more than 4 weeks prior to study entry.
No patients that have received systemic antifungal therapy at doses greater than 0.5 mg/kg/day for conventional or lipid formulations of amphotericin B or greater than 200 mg/day of itraconazole, for more than 96 hours during the two week period prior to study entry.
No patients with a diagnosis of CMV pneumonia.
No pregnant or lactating females.
No patients with a history of hypersensitivity or intolerance to azole antifungal agents including miconazole, ketoconazole, fluconazole, or itraconazole.
No patients with a history of hypersensitivity or severe intolerance (despite supportive therapy) to conventional or a lipid formulation of amphotericin B.
No subjects who are receiving and cannot discontinue the following drugs at least 24 hours prior to randomization: Terfenadine, cisapride and astemizole (due to the possibility of QTc prolongation); Sulphonylureas (as these compounds have a narrow therapeutic window and an increase in plasma levels may lead to hypoglycemia).
No subjects who have received the following drugs within 14 days prior to randomization: Rifampin, carbamazepine and barbiturates as these are potent inducers of hepatic enzymes and will result in undetectable levels of voriconazole.
No patients who are receiving or are likely to received any investigational drug (any unlicensed new chemical entity), except one of the following classes of medications: cancer chemotherapeutic agents, antiretrovirals, therapies for HIV/AIDS-related opportunistic infections.
No patients who are receiving the following medications or treatments during the study period: G-CSF or GM-CSF (for other than of granulocytopenia) any systemic antifungal medication active against Aspergillus white blood cell transfusions.
No patients with the following abnormalities of liver function tests: AST, ALT greater than 5x ULN (upper limit normal); alkaline phosphatase, total bilirubin greater than 5x ULN.
No patients with renal insufficiency that would contraindicate treatment with initial randomized therapy (serum creatinine greater than 2.5 mg/dl).
No patients with a life expectancy of less than 72 hours.
No patients on artificial ventilation, unlikely to be extubated within 24 hours of study entry.
No patients for whom written informed consent cannot be obtained.
No patients that have already participated in this trial.
No patients with any condition which, in the opinion of the investigator, could affect patient safety, preclude evaluation of response, or render it unlikely that the contemplated course of therapy can be completed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Invasive aspergillosis is a fungal disease which is increasing in incidence with the increase in immunocompromised persons in our population. Persons with prolonged neutropenia secondary to cytotoxic chemotherapies are at the highest risk for acute aspergillosis. Patients undergoing bone marrow transplantation, receiving prolonged corticosteroid or other immunosuppressive therapies, and persons with HIV infection and AIDS are also at risk. Even with antifungal therapy, aspergillosis in its acute invasive forms has a high mortality. In bone marrow transplantation patients and in those whose infection involves the brain, this mortality is greater than 90%. Amphotericin B in its conventional form, is the current standard treatment for this disease. Response to therapy with amphotericin B usually ranges between 20-60% in most studies. The higher response rates are usually seen in those patients who can tolerate this agent for at least 14 days. Because of its nephrotoxicity and other adverse effects, alternatives to conventional amphotericin B have been sought. These currently include liposomal forms of amphotericin B and itraconazole. Although these forms show a decrease in adverse effects, the efficacy of these drugs has not been shown to be equivalent to conventional amphotericin B.
Voriconazole is an investigational antifungal drug currently being brought to phase III trials in the US. This azole has been shown active against Aspergillus spp. in vitro, and in animal models and early human trials to be effective against aspergillosis. It has been shown to be well-tolerated and is available in an intravenous and oral formulation.
This study will evaluate the efficacy, safety, and toleration of voriconazole compared to conventional therapy with amphotericin B as primary treatment of acute invasive aspergillosis in immunocompromised patients. Patients will be randomized to open-labelled therapy with voriconazole or amphotericin B in a one-to-one ratio.
Read the detailed description
Invasive aspergillosis is a fungal disease which is increasing in incidence with the increase in immunocompromised persons in our population. Persons with prolonged neutropenia secondary to cytotoxic chemotherapies are at the highest risk for acute aspergillosis. Patients undergoing bone marrow transplantation, receiving prolonged corticosteroid or other immunosuppressive therapies, and persons with HIV infection and AIDS are also at risk. Even with antifungal therapy, aspergillosis in its acute invasive forms has a high mortality. In bone marrow transplantation patients and in those whose infection involves the brain, this mortality is greater than 90%. Amphotericin B, in its conventional form, is the current standard treatment for this disease. Response to therapy with amphotericin B usually ranges between 20-60% in most studies. The higher response rates are usually seen in those patients who can tolerate this agent for at least 14 days. Because of its nephrotoxicity and other adverse effects, alternatives to conventional amphotericin B have been sought. These currently include liposomal forms of amphotericin B and itraconazole. Although these forms show a decrease in adverse effects, the efficacy of these drugs has not been shown to be equivalent to conventional amphotericin B.
Voriconazole is an investigational antifungal drug currently being brought to phase III trials in the U.S. This azole has been shown active against Aspergillus sp. in vitro, and in animal models and early human trials to be effective against aspergillosis. It has been shown to be well-tolerated and is available in an intravenous and oral formulation.
This study will evaluate the efficacy, safety, and toleration of voriconazole compared to conventional therapy with amphotericin B as primary treatment of acute invasive aspergillosis in immunocompromised patients. Although the original protocol allows enrollment of subjects older than 12 years old we do not expect to enroll patients younger than 18 years old. Patients will be randomized to open-labelled therapy with voriconazole or amphotericin B in a one-to-one ratio.
- Conditions
- Acquired Immunodeficiency Syndrome, Aspergillosis, HIV Infections, Immunologic Deficiency Syndromes, Neutropenia
- Being tested
- Voriconazole, Amphotericin B
- Keywords
- Aspergillus, Azole, Immunocompromise
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Aspergillosis, HIV Infections, Immunologic Deficiency Syndromes, Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VoriconazoleDrug
Amphotericin BDrug
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 startAug 1997
- Study completionAug 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acquired Immunodeficiency SyndromeStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)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 3
- Primary purpose
- Treatment
- Enrolment
- 10 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001646
- Sponsor's protocol ID
- 970164
- Other IDs
- 97-I-0164
- Status last verified
- Sep 1999
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975 Mar;31(1):103-15.
PubMed 1100130
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
- Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
- ClinicalTrials.gov ID
- NCT00001646
- Acronym / sponsor ID
- 970164
- Conditions
- Acquired Immunodeficiency Syndrome, Aspergillosis, HIV Infections, Immunologic Deficiency Syndromes, Neutropenia
- Keywords
- Aspergillus, Azole, Immunocompromise
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Aug 1997
- Study completion
- Aug 2000
- 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.
Invasive aspergillosis is a fungal disease which is increasing in incidence with the increase in immunocompromised persons in our population. Persons with prolonged neutropenia secondary to cytotoxic chemotherapies are at the highest risk for acute aspergillosis. Patients undergoing bone marrow transplantation, receiving prolonged corticosteroid or other immunosuppressive therapies, and persons with HIV infection and AIDS are also at risk. Even with antifungal therapy, aspergillosis in its acute invasive forms has a high mortality. In bone marrow transplantation patients and in those whose infection involves the brain, this mortality is greater than 90%. Amphotericin B in its conventional form, is the current standard treatment for this disease. Response to therapy with amphotericin B usually ranges between 20-60% in most studies. The higher response rates are usually seen in those patients who can tolerate this agent for at least 14 days. Because of its nephrotoxicity and other adverse effects, alternatives to conventional amphotericin B have been sought. These currently include liposomal forms of amphotericin B and itraconazole. Although these forms show a decrease in adverse effects, the efficacy of these drugs has not been shown to be equivalent to conventional amphotericin B.
Voriconazole is an investigational antifungal drug currently being brought to phase III trials in the US. This azole has been shown active against Aspergillus spp. in vitro, and in animal models and early human trials to be effective against aspergillosis. It has been shown to be well-tolerated and is available in an intravenous and oral formulation.
This study will evaluate the efficacy, safety, and toleration of voriconazole compared to conventional therapy with amphotericin B as primary treatment of acute invasive aspergillosis in immunocompromised patients. Patients will be randomized to open-labelled therapy with voriconazole or amphotericin B in a one-to-one ratio.
Detailed description
Invasive aspergillosis is a fungal disease which is increasing in incidence with the increase in immunocompromised persons in our population. Persons with prolonged neutropenia secondary to cytotoxic chemotherapies are at the highest risk for acute aspergillosis. Patients undergoing bone marrow transplantation, receiving prolonged corticosteroid or other immunosuppressive therapies, and persons with HIV infection and AIDS are also at risk. Even with antifungal therapy, aspergillosis in its acute invasive forms has a high mortality. In bone marrow transplantation patients and in those whose infection involves the brain, this mortality is greater than 90%. Amphotericin B, in its conventional form, is the current standard treatment for this disease. Response to therapy with amphotericin B usually ranges between 20-60% in most studies. The higher response rates are usually seen in those patients who can tolerate this agent for at least 14 days. Because of its nephrotoxicity and other adverse effects, alternatives to conventional amphotericin B have been sought. These currently include liposomal forms of amphotericin B and itraconazole. Although these forms show a decrease in adverse effects, the efficacy of these drugs has not been shown to be equivalent to conventional amphotericin B.
Voriconazole is an investigational antifungal drug currently being brought to phase III trials in the U.S. This azole has been shown active against Aspergillus sp. in vitro, and in animal models and early human trials to be effective against aspergillosis. It has been shown to be well-tolerated and is available in an intravenous and oral formulation.
This study will evaluate the efficacy, safety, and toleration of voriconazole compared to conventional therapy with amphotericin B as primary treatment of acute invasive aspergillosis in immunocompromised patients. Although the original protocol allows enrollment of subjects older than 12 years old we do not expect to enroll patients younger than 18 years old. Patients will be randomized to open-labelled therapy with voriconazole or amphotericin B in a one-to-one ratio.
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 | – |
| Amphotericin B | 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 1100130Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975 Mar;31(1):103-15.
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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 3 study testing Voriconazole and Amphotericin B in people with Acquired Immunodeficiency Syndrome and Aspergillosis, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 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?
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 NCT00001646, 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 4 Mar 2008.