HIV InfectionsPhase 2NCT00000838
Antiviral Activity of and Resistance to Lamivudine in Combination With Zidovudine, Stavudine, or Didanosine
A Phase 2 study testing Lamivudine, Stavudine and Zidovudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 32 sites in 2 countries.
Trial summary
To evaluate the efficacy, safety, and pharmacokinetics of lamivudine (3TC) combined with zidovudine (AZT), stavudine (d4T), or didanosine (ddI) in comparison with d4T or ddI monotherapy in HIV-infected patients with no prior nucleoside therapy. 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?
- Lamivudine, Stavudine and Zidovudine
- How many people
- 256 participants
- Where
- 32 sitesin 2 countries
- Study dates
- Start not givento Mar 1998
- Phase
- Phase 2
- 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:
- PCP prophylaxis.
- Patients must have:
- HIV infection.
- CD4 count 200 - 600 cells/mm3.
- Life expectancy of at least 24 weeks.
- Consent of parent or guardian if less than 18 years old.
Who cannot join
- Co-existing Condition:
- Patients with the following symptoms or conditions are excluded:
- Unexplained temperature >= 38.5 C for 7 consecutive days within 30 days prior to study entry.
- PER AMENDMENT 1/25/96:
- A malignancy that requires systemic chemotherapies other than Kaposi's sarcoma.
- Concurrent Medication:
Show all 19Show fewer
- Excluded:
- Concurrent other antiretroviral or immunologic agents.
- Other experimental therapies.
- Systemic corticosteroids (except as adjuvant therapy for acute PCP) and other immunosuppressive drugs.
- Systemic cytotoxic chemotherapy.
- Induction or maintenance with foscarnet or ganciclovir (oral or IV).
- Patients with the following prior conditions are excluded:
- History of acute or chronic pancreatitis.
- History of grade 2 or higher peripheral neuropathy.
- Prior Medication:
- Excluded:
- Antiretrovirals within 90 days prior to study entry.
- More than 7 days total lifetime use of any antiretroviral nucleoside.
Trial locations and contacts
32 sites in 2 countries.
32 sites in 2 countries
United States31 sites
University of Colorado Hospital CRS
Aurora, Colorado, 80262
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, 21287
Alabama Therapeutics CRS
Birmingham, Alabama
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, 14215
Unc Aids Crs
Chapel Hill, North Carolina
Carolinas HealthCare System, Carolinas Med. Ctr.
Charlotte, North Carolina
Cook County Hosp. CORE Ctr.
Chicago, Illinois, 60612
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, 60612
Weiss Memorial Hosp.
Chicago, Illinois, 60640
Northwestern University CRS
Chicago, Illinois
MetroHealth CRS
Cleveland, Ohio, 44109
The Ohio State University Medical Center
Columbus, Ohio, 43210
Regional Center for Infectious Disease, Wendover Medical Center CRS
Greensboro, North Carolina
Queens Med. Ctr.
Honolulu, Hawaii, 96816
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, 96816
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 46202
Methodist Hosp. of Indiana
Indianapolis, Indiana, 46202
UCLA CARE Center CRS
Los Angeles, California, 90095
Univ. of Miami AIDS CRS
Miami, Florida, 33136
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, 10003
NYU Med. Ctr., Dept. of Medicine
New York, New York, 10016
Stanford CRS
Palo Alto, California, 94115
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104
Univ. of Rochester ACTG CRS
Rochester, New York
Ucsd, Avrc Crs
San Diego, California, 92103
Santa Clara Valley Med. Ctr.
San Jose, California, 95128
San Mateo County AIDS Program
San Mateo, California
University of Washington AIDS CRS
Seattle, Washington, 98122
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, 63112
Washington U CRS
St Louis, Missouri
About this study
Official title: A Phase II, Randomized Study of the Antiviral Activity and Resistance Interactions of Lamivudine (3TC) in Combination With Zidovudine (AZT), Stavudine (d4T), or Didanosine (ddI) Versus Monotherapy With ddI or d4T in HIV-Infected Individuals With 200 - 600 CD4+ Cells/mm3 and No Previous Nucleoside Experience
To evaluate the efficacy, safety, and pharmacokinetics of lamivudine (3TC) combined with zidovudine (AZT), stavudine (d4T), or didanosine (ddI) in comparison with d4T or ddI monotherapy in HIV-infected patients with no prior nucleoside therapy.
3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.
Read the detailed description
3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.
Patients are randomized to either a ddI limb or d4T limb, then randomized a second time to one of six treatment arms, as follows: ddI alone, d4T alone, 3TC/AZT (on both ddI and d4T limbs), 3TC/ddI, and 3TC/d4T. Treatment is given for 48 weeks. At study week 24, patients on monotherapy will have 3TC added to their regimen (in a blinded fashion).
PER AMENDMENT 10/18/96: A treatment extension phase has been added to the study design in order to allow subjects who complete 48 weeks of therapy to remain on their same blinded treatment until approximately 2 months after the last enrolled subject completes 48 weeks on the study.
- Conditions
- HIV Infections
- Being tested
- Lamivudine, Stavudine, Zidovudine, Didanosine
- Keywords
- Didanosine, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Antiviral Agents, Zidovudine, Stavudine, Lamivudine
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome, AIDS-Related Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LamivudineDrug
StavudineDrug
ZidovudineDrug
DidanosineDrug
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 completionMar 1998
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)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 2
- Primary purpose
- Treatment
- Enrolment
- 256 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kuritzkes D, Study chairJohnson V, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000838
- Sponsor's protocol ID
- ACTG 306
- Other IDs
- 11281
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
Marschner I, Betensky RA, Degruttola V, Kuritzkes DR. Biases in the assessment of viral load reduction in HIV clinical trials. Int Conf AIDS. 1998;12:802 (abstract no 42149)
Hill A, Demasi R, Kuhn M. Different analyses give highly variable estimates of HIV-1 RNA undetectability and log reduction in clinical trials. Int Conf AIDS. 1998;12:813-4 (abstract no 42204)
Kuritzkes DR, Marschner IC, Johnson VA, Bassett RL, Eron JJ, Fischl MA, Boone G, Skovronski J, Wood K, Bell DL, Pettinelli CB, Sommadossi JP. A randomized, double-blind, placebo-controlled trial of lamivudine (3TC) in combination with zidovudine (ZDV), stavudine (d4T), or didanosine (ddI) in treatment naive patients. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 1)
Kuritzkes DR, Marschner I, Johnson VA, Bassett R, Eron JJ, Fischl MA, Murphy RL, Fife K, Maenza J, Rosandich ME, Bell D, Wood K, Sommadossi JP, Pettinelli C. Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators. AIDS. 1999 Apr 16;13(6):685-94. doi: 10.1097/00002030-199904160-00009.
PubMed 10397563Kuritzkes DR, Bassett RL, Hazelwood JD, Barrett H, Rhodes RA, Young RK, Johnson VA; Adult ACTG Protocol 306 370 Teams. Rate of thymidine analogue resistance mutation accumulation with zidovudine- or stavudine-based regimens. J Acquir Immune Defic Syndr. 2004 May 1;36(1):600-3. doi: 10.1097/00126334-200405010-00008.
PubMed 15097303Fisher M. Nucleoside combinations for antiretroviral therapy: efficacy of stavudine in combination with either didanosine or lamivudine. AIDS. 1998;12 Suppl 3:S9-16.
PubMed 15168718
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized Study of the Antiviral Activity and Resistance Interactions of Lamivudine (3TC) in Combination With Zidovudine (AZT), Stavudine (d4T), or Didanosine (ddI) Versus Monotherapy With ddI or d4T in HIV-Infected Individuals With 200 - 600 CD4+ Cells/mm3 and No Previous Nucleoside Experience
- ClinicalTrials.gov ID
- NCT00000838
- Acronym / sponsor ID
- ACTG 306
- Conditions
- HIV Infections
- Keywords
- Didanosine, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Antiviral Agents, Zidovudine, Stavudine, Lamivudine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 256 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Mar 1998 (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 efficacy, safety, and pharmacokinetics of lamivudine (3TC) combined with zidovudine (AZT), stavudine (d4T), or didanosine (ddI) in comparison with d4T or ddI monotherapy in HIV-infected patients with no prior nucleoside therapy.
3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.
Detailed description
3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.
Patients are randomized to either a ddI limb or d4T limb, then randomized a second time to one of six treatment arms, as follows: ddI alone, d4T alone, 3TC/AZT (on both ddI and d4T limbs), 3TC/ddI, and 3TC/d4T. Treatment is given for 48 weeks. At study week 24, patients on monotherapy will have 3TC added to their regimen (in a blinded fashion).
PER AMENDMENT 10/18/96: A treatment extension phase has been added to the study design in order to allow subjects who complete 48 weeks of therapy to remain on their same blinded treatment until approximately 2 months after the last enrolled subject completes 48 weeks on the study.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- PCP prophylaxis.
- HIV infection.
- CD4 count 200 - 600 cells/mm3.
- Life expectancy of at least 24 weeks.
- Consent of parent or guardian if less than 18 years old.
Key exclusion criteria (19 listed)
- Unexplained temperature >= 38.5 C for 7 consecutive days within 30 days prior to study entry.
- A malignancy that requires systemic chemotherapies other than Kaposi's sarcoma.
- Concurrent other antiretroviral or immunologic agents.
- Other experimental therapies.
- Systemic corticosteroids (except as adjuvant therapy for acute PCP) and other immunosuppressive drugs.
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 |
|---|---|---|
| Lamivudine | Drug | – |
| Stavudine | Drug | – |
| Zidovudine | Drug | – |
| Didanosine | 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 Nov 2021.
- BackgroundMarschner I, Betensky RA, Degruttola V, Kuritzkes DR. Biases in the assessment of viral load reduction in HIV clinical trials. Int Conf AIDS. 1998;12:802 (abstract no 42149)
- BackgroundHill A, Demasi R, Kuhn M. Different analyses give highly variable estimates of HIV-1 RNA undetectability and log reduction in clinical trials. Int Conf AIDS. 1998;12:813-4 (abstract no 42204)
- BackgroundKuritzkes DR, Marschner IC, Johnson VA, Bassett RL, Eron JJ, Fischl MA, Boone G, Skovronski J, Wood K, Bell DL, Pettinelli CB, Sommadossi JP. A randomized, double-blind, placebo-controlled trial of lamivudine (3TC) in combination with zidovudine (ZDV), stavudine (d4T), or didanosine (ddI) in treatment naive patients. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 1)
- Background: PubMed 10397563Kuritzkes DR, Marschner I, Johnson VA, Bassett R, Eron JJ, Fischl MA, Murphy RL, Fife K, Maenza J, Rosandich ME, Bell D, Wood K, Sommadossi JP, Pettinelli C. Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators. AIDS. 1999 Apr 16;13(6):685-94. doi: 10.1097/00002030-199904160-00009.
- Background: PubMed 15097303Kuritzkes DR, Bassett RL, Hazelwood JD, Barrett H, Rhodes RA, Young RK, Johnson VA; Adult ACTG Protocol 306 370 Teams. Rate of thymidine analogue resistance mutation accumulation with zidovudine- or stavudine-based regimens. J Acquir Immune Defic Syndr. 2004 May 1;36(1):600-3. doi: 10.1097/00126334-200405010-00008.
- Background: PubMed 15168718Fisher M. Nucleoside combinations for antiretroviral therapy: efficacy of stavudine in combination with either didanosine or lamivudine. AIDS. 1998;12 Suppl 3:S9-16.
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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.
Kuritzkes D study chair
Johnson V study chair
32 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lamivudine, Stavudine and Zidovudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 32 sites in 2 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 8 inclusion and 19 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 4 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 32 sites in United States, Puerto Rico. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 NCT00000838, which also lists 6 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 Nov 2021.