HIV InfectionsPhase 1NCT00000696
A Phase I/II Open Label Study To Evaluate the Antiviral Potential of Combination Low-Dose Therapy With Zidovudine and Interferon-Alpha 2A in Patients With Symptomatic HIV Disease
A Phase 1 study testing Interferon alfa-2a and Zidovudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.
Trial summary
To evaluate the anti-HIV effect of single agent versus combination therapy with zidovudine (AZT) and interferon alfa-2a (IFN-A2a), as measured by p24 protein expression, viral growth and infectivity in patients with symptomatic HIV disease. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Interferon alfa-2a and Zidovudine
- How many people
- 48 participants
- Where
- 6 sitesUnited States
- Study dates
- Start not givento Nov 1993
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Concurrent Medication:
- Allowed:
- Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), as aerosolized pentamidine.
- Ibuprofen.
- Acute therapy (7 days) with oral acyclovir.
- Acute therapy with ketoconazole.
Show all 11Show fewer
- Patients must have:
- A diagnosis of AIDS related complex as well as defined symptoms within 12 months of study entry in the absence of concurrent illness or conditions other than HIV infection.
- Estimated life expectancy of at least 12 weeks.
- Positive serum p24 antigen > 70 pg/ml. Patients may have received prior zidovudine (AZT) and / or interferon alpha therapy, provided that:
- The total duration of treatment was < 6 months. Patients treated > 12 weeks but < 6 months should have received continuous therapy (no more than 14 consecutive days or 21 total days off during the treatment period). For patients treated = or < 12 weeks, continuous treatment means < 7 days off total during the treatment period. For all patients, a washout period of = or > 4 weeks must have elapsed prior to study entry. Treatment did not result in a major adverse reaction attributable to AZT or IFN-A2a such that rechallenge at a randomly assigned dosage level would be precluded.
Who cannot join
- Co-existing Condition:
- Patients with the following are excluded:
- Acquired immunodeficiency syndrome (AIDS) as defined by opportunistic infections.
- Significant cardiac (New York Heart Association Class 3 or 4), hepatic, renal, or neurologic disorder.
- Concurrent neoplasm other than basal cell carcinoma or in situ carcinoma of the cervix.
- Significant neurological disorder which impairs the patient's ability to give or receive informed consent or reduces the patient's performance status to the extent that protocol requirements and self-administration of drug cannot be accurately completed.
Show all 43Show fewer
- Concurrent Medication:
- Excluded:
- All concomitant medications should be kept to a minimum.
- Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), other than aerosolized pentamidine.
- Other antiretroviral agents.
- Experimental medications.
- Biologic response modifiers.
- Systemic corticosteroids.
- Cimetidine.
- Ranitidine.
- Aspirin, acetaminophen, and nonsteroidal anti-inflammatory agents with the exception of ibuprofen.
- Barbiturates.
- Cardiac glycosides, antiarrhythmics, or vasodilators.
- Systemic treatment for an active infection, including pulmonary tuberculosis.
- Concurrent Treatment:
- Excluded:
- Systemic treatment for an active infection, including pulmonary tuberculosis.
- Patients with the following will be excluded from the study:
- AIDS as defined by opportunistic infections, Kaposi's sarcoma, or other AIDS defining neoplasms, HIV dementia complex, or HIV wasting disease.
- HIV constitutional disease. Any one of the following:
- Fever of > 38.5 degrees persisting for > 1 month.
- Involuntary weight loss of = or > 10 lbs or 10 percent of body weight.
- Diarrhea defined as = or > 2 liquid stools per day persisting for at least a total of 14 days without definable cause.
- Significant cardiac (New York Heart Association Class 3 or 4), hepatic, renal, or neurologic disorder.
- Concurrent neoplasm other than basal cell carcinoma or in situ carcinoma of the cervix.
- Significant neurological disorder which impairs the patient's ability to give or receive informed consent or reduces the patient's performance status to the extent that protocol requirements and self-administration of drug cannot be accurately completed.
- Prior AZT or IFN-A2a therapy for = or > 6 months.
- Previous major adverse reaction to AZT or IFN-A2a.
- Prior Medication:
- Excluded:
- Prior zidovudine (AZT) or interferon therapy for = or > 6 months.
- Excluded within 4 weeks of study entry:
- Any antiretroviral agent, Cytotoxic chemotherapy, or immunomodulator, including corticosteroids.
- Excluded within 30 days of study entry:
- Anti-infectives or agents likely to produce hematologic side effects (e.g., trimethoprim / sulfamethoxazole).
- Excluded: Cardiac glycosides, antiarrhythmics, or vasodilators.
- Active substance abuse.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts
USC CRS
Los Angeles, California, 90033
Univ. of Miami AIDS CRS
Miami, Florida
University of Minnesota, ACTU
Minneapolis, Minnesota, 55455
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, 10029
About this study
To evaluate the anti-HIV effect of single agent versus combination therapy with zidovudine (AZT) and interferon alfa-2a (IFN-A2a), as measured by p24 protein expression, viral growth and infectivity in patients with symptomatic HIV disease. To assess the safety of low dose schedules of AZT and IFN-A2a, alone and in combination, as measured by neutrophil counts and hepatic transaminase levels. To evaluate the comparative effects of single agent versus combination therapy with AZT and IFN-A2a on CD4 cell counts and skin test reactivity.
AZT is known to be an effective treatment for HIV infection. However, patients may develop reactions to AZT when it is administered for long periods of time. Combining AZT with another drug at lower doses might reduce toxicity in patients and prevent the development of drug resistant strains. IFN-A2a can reduce the growth of HIV in test tube experiments and recent studies have shown that when AZT and IFN-A2a are used together they reduce the growth of HIV more effectively than when either drug is used alone. This study will examine the effectiveness and safety of these drugs when they are given together and compare these results with the effectiveness and safety of the drugs when they are used alone.
Read the detailed description
AZT is known to be an effective treatment for HIV infection. However, patients may develop reactions to AZT when it is administered for long periods of time. Combining AZT with another drug at lower doses might reduce toxicity in patients and prevent the development of drug resistant strains. IFN-A2a can reduce the growth of HIV in test tube experiments and recent studies have shown that when AZT and IFN-A2a are used together they reduce the growth of HIV more effectively than when either drug is used alone. This study will examine the effectiveness and safety of these drugs when they are given together and compare these results with the effectiveness and safety of the drugs when they are used alone.
AMENDED: 04-18-91 Treatment extended to 96 weeks. Patients are seen weekly for the first month and for the month following initiation of combination therapy (Cohorts 1, 2), then every other week until treatment week 48, followed by every week for the duration of the study. AMENDED: The doses have been modified to one of 4 total daily doses of AZT and one of 4 daily doses of IFN-A2a. AMENDED: Total treatment period will be 48 weeks. AMENDED: 9-24-90 Treatment will end 901214. Original Design: Before beginning any treatment, patients are carefully examined and evaluated. Each patient receives medication for 24 weeks, followed by a 4-week follow-up period. Patients are assigned randomly to one of four dosing schedules within one of three groups stratified according to whether or not they have ever received AZT and / or IFN-A2a:
- Group 1 receives AZT alone for 12 weeks, then AZT plus IFN-A2a for the following 12 weeks.
- Group 2 receives IFN-A2a alone for 12 weeks, then IFN-A2a plus AZT for the following 12 weeks.
- Group 3 receives the combination of AZT and IFN-A2a for 24 weeks. Medications are administered according to one of four possible daily dosing schedules of AZT plus IFN-A2a (increasing doses of each). AZT is taken by mouth as a capsule every 6 hours. IFN-A2a is given by an injection under the skin once a day. Initially, doses of IFN-A2a are given by one of the research staff, after which patients are taught to give their own injections. Patients are examined weekly for the first 4 weeks, then every other week until the end of the study. Patients assigned to groups receiving two drugs will be examined weekly again for 4 weeks when the second drug is added.
- Conditions
- HIV Infections
- Being tested
- Interferon alfa-2a, Zidovudine
- Keywords
- Interferon Alfa-2a, Drug Therapy, Combination, AIDS-Related Complex, Zidovudine
- Medical subject headings
- HIV Infections, AIDS-Related Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon alfa-2aDrug
ZidovudineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionNov 1993
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies 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 1
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 48 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- D Mildvan, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000696
- Sponsor's protocol ID
- ACTG 068
- Other IDs
- 11042
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 2 Nov 2021
- Results posted
- No
Publications
Zucker ML, Huberman KT, Hirschman SZ, Mildvan D. Stability of HIV-1 p24 antigen upon prolonged storage at -70 degrees C. The ACTG 068 Collaborative Team. Int Conf AIDS. 1992 Jul 19-24;8(3):44 (abstract no PuA 6203)
Mildvan D, Bassiakos Y. Zidovudine (ZDV) and interferon-alpha 2a (IFN): ongoing assessment of synergy and tolerance in early ARC patients, ACTG 068. The ACTG 068 Collaborative Group. Int Conf AIDS. 1992 Jul 19-24;8(2):B184 (abstract no PoB 3586)
Mildvan D, Ruprecht R, Krown S, Pettinelli C. Methodological issues in AIDS clinical trials. Application of the combination index method in the design of a clinical antiretroviral trial: ACTG 068. J Acquir Immune Defic Syndr (1988). 1990;3 Suppl 2:S111-3 discussion S114-9. No abstract available.
PubMed 2231291Mildvan D, Bassiakos Y, Zucker ML, Hyslop N Jr, Krown SE, Sacks HS, Zachary J, Paredes J, Fessel WJ, Rhame F, Kramer F, Fischl MA, Poiesz B, Wood K, Ruprecht RM, Kim J, Grossberg SE, Kasdan P, Berge P, Marshak A, Pettinelli C. Synergy, activity and tolerability of zidovudine and interferon-alpha in patients with symptomatic HIV-1 infection: AIDS Clincal Trial Group 068. Antivir Ther. 1996 Apr;1(2):77-88.
PubMed 11321183
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Open Label Study To Evaluate the Antiviral Potential of Combination Low-Dose Therapy With Zidovudine and Interferon-Alpha 2A in Patients With Symptomatic HIV Disease
- ClinicalTrials.gov ID
- NCT00000696
- Acronym / sponsor ID
- ACTG 068
- Conditions
- HIV Infections
- Keywords
- Interferon Alfa-2a, Drug Therapy, Combination, AIDS-Related Complex, Zidovudine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Nov 1993 (actual)
- First posted
- 31 Aug 2001 (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.
To evaluate the anti-HIV effect of single agent versus combination therapy with zidovudine (AZT) and interferon alfa-2a (IFN-A2a), as measured by p24 protein expression, viral growth and infectivity in patients with symptomatic HIV disease. To assess the safety of low dose schedules of AZT and IFN-A2a, alone and in combination, as measured by neutrophil counts and hepatic transaminase levels. To evaluate the comparative effects of single agent versus combination therapy with AZT and IFN-A2a on CD4 cell counts and skin test reactivity.
AZT is known to be an effective treatment for HIV infection. However, patients may develop reactions to AZT when it is administered for long periods of time. Combining AZT with another drug at lower doses might reduce toxicity in patients and prevent the development of drug resistant strains. IFN-A2a can reduce the growth of HIV in test tube experiments and recent studies have shown that when AZT and IFN-A2a are used together they reduce the growth of HIV more effectively than when either drug is used alone. This study will examine the effectiveness and safety of these drugs when they are given together and compare these results with the effectiveness and safety of the drugs when they are used alone.
Detailed description
AZT is known to be an effective treatment for HIV infection. However, patients may develop reactions to AZT when it is administered for long periods of time. Combining AZT with another drug at lower doses might reduce toxicity in patients and prevent the development of drug resistant strains. IFN-A2a can reduce the growth of HIV in test tube experiments and recent studies have shown that when AZT and IFN-A2a are used together they reduce the growth of HIV more effectively than when either drug is used alone. This study will examine the effectiveness and safety of these drugs when they are given together and compare these results with the effectiveness and safety of the drugs when they are used alone.
AMENDED: 04-18-91 Treatment extended to 96 weeks. Patients are seen weekly for the first month and for the month following initiation of combination therapy (Cohorts 1, 2), then every other week until treatment week 48, followed by every week for the duration of the study. AMENDED: The doses have been modified to one of 4 total daily doses of AZT and one of 4 daily doses of IFN-A2a. AMENDED: Total treatment period will be 48 weeks. AMENDED: 9-24-90 Treatment will end 901214. Original Design: Before beginning any treatment, patients are carefully examined and evaluated. Each patient receives medication for 24 weeks, followed by a 4-week follow-up period. Patients are assigned randomly to one of four dosing schedules within one of three groups stratified according to whether or not they have ever received AZT and / or IFN-A2a:
- Group 1 receives AZT alone for 12 weeks, then AZT plus IFN-A2a for the following 12 weeks.
- Group 2 receives IFN-A2a alone for 12 weeks, then IFN-A2a plus AZT for the following 12 weeks.
- Group 3 receives the combination of AZT and IFN-A2a for 24 weeks. Medications are administered according to one of four possible daily dosing schedules of AZT plus IFN-A2a (increasing doses of each). AZT is taken by mouth as a capsule every 6 hours. IFN-A2a is given by an injection under the skin once a day. Initially, doses of IFN-A2a are given by one of the research staff, after which patients are taught to give their own injections. Patients are examined weekly for the first 4 weeks, then every other week until the end of the study. Patients assigned to groups receiving two drugs will be examined weekly again for 4 weeks when the second drug is added.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), as aerosolized pentamidine.
- Ibuprofen.
- Acute therapy (7 days) with oral acyclovir.
- Acute therapy with ketoconazole.
- A diagnosis of AIDS related complex as well as defined symptoms within 12 months of study entry in the absence of concurrent illness or conditions other than HIV infection.
Key exclusion criteria (43 listed)
- Acquired immunodeficiency syndrome (AIDS) as defined by opportunistic infections.
- Significant cardiac (New York Heart Association Class 3 or 4), hepatic, renal, or neurologic disorder.
- Concurrent neoplasm other than basal cell carcinoma or in situ carcinoma of the cervix.
- Significant neurological disorder which impairs the patient's ability to give or receive informed consent or reduces the patient's performance status to the extent that protocol requirements and self-administration of drug cannot be accurately completed.
- All concomitant medications should be kept to a minimum.
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 |
|---|---|---|
| Interferon alfa-2a | Drug | – |
| Zidovudine | 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 2 Nov 2021.
- BackgroundZucker ML, Huberman KT, Hirschman SZ, Mildvan D. Stability of HIV-1 p24 antigen upon prolonged storage at -70 degrees C. The ACTG 068 Collaborative Team. Int Conf AIDS. 1992 Jul 19-24;8(3):44 (abstract no PuA 6203)
- BackgroundMildvan D, Bassiakos Y. Zidovudine (ZDV) and interferon-alpha 2a (IFN): ongoing assessment of synergy and tolerance in early ARC patients, ACTG 068. The ACTG 068 Collaborative Group. Int Conf AIDS. 1992 Jul 19-24;8(2):B184 (abstract no PoB 3586)
- Background: PubMed 2231291Mildvan D, Ruprecht R, Krown S, Pettinelli C. Methodological issues in AIDS clinical trials. Application of the combination index method in the design of a clinical antiretroviral trial: ACTG 068. J Acquir Immune Defic Syndr (1988). 1990;3 Suppl 2:S111-3 discussion S114-9. No abstract available.
- Background: PubMed 11321183Mildvan D, Bassiakos Y, Zucker ML, Hyslop N Jr, Krown SE, Sacks HS, Zachary J, Paredes J, Fessel WJ, Rhame F, Kramer F, Fischl MA, Poiesz B, Wood K, Ruprecht RM, Kim J, Grossberg SE, Kasdan P, Berge P, Marshak A, Pettinelli C. Synergy, activity and tolerability of zidovudine and interferon-alpha in patients with symptomatic HIV-1 infection: AIDS Clincal Trial Group 068. Antivir Ther. 1996 Apr;1(2):77-88.
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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.
D Mildvan study chair
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Interferon alfa-2a and Zidovudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.
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 11 inclusion and 43 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 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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 NCT00000696, which also lists 4 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 2 Nov 2021.