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AzTrials

HIV InfectionsPhase 2NCT00000671

A Phase II Efficacy Study Comparing 2',3'-Dideoxyinosine (ddI) (BMY-40900) and Zidovudine Therapy of Patients With HIV Infection Who Have Been on Long Term Zidovudine Treatment

A Phase 2 study testing Zidovudine and Didanosine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 71 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

To compare the effectiveness and toxicity of didanosine (ddI) and zidovudine (AZT) in patients with AIDS or advanced AIDS-related complex (ARC) who have tolerated AZT therapy for 12 months or longer. Per amendment, asymptomatic patients with CD4 counts less than 200 cells/mm3 are eligible. 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?
Zidovudine and Didanosine
How many people
750 participants
Where
71 sitesin 2 countries
Study dates
Start not givento Mar 1992
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:
  • Required:
  • Aerosolized pentamidine (300 mg every 4 weeks).
  • Allowed:
  • Chronic suppressive treatment for toxoplasmosis, Pneumocystis carinii pneumonia (PCP), cryptococcal meningitis, herpes simplex virus infection.
  • Ganciclovir for patients developing cytomegalovirus (CMV) infection while in study.
Show all 26Show fewer
  • Erythropoietin for patients under the relevant treatment IND.
  • Treatment of opportunistic infections with other than sulfonamide-containing regimens.
  • Aspirin, acetaminophen, or non-steroidal anti-inflammatory agents is discouraged, but is permitted for as short a period of time as possible.
  • Chronic use of trimethoprim - sulfamethoxazole or other sulfonamide preparations is not encouraged while on study.
  • Patients must:
  • Have had the diagnosis of AIDS or advanced AIDS related complex (ARC).
  • Have received AZT therapy for at least 12 months, with a minimal daily dose of 500 mg/day and with no more than 60 days off AZT therapy within the 12 month period; medical records with documentation of AZT dosing must be provided.
  • Provide informed consent (guardian as appropriate).
  • Be available for follow-up for at least 6 months.
  • Have the inclusion laboratory values within approximately 14 days of initiating therapy (except for CD4 cell counts).
  • Patients whose AIDS-defining condition is Kaposi's sarcoma alone must have CD4 cell counts < 300 cells/mm3.
  • Allowed:
  • Positive blood culture for Mycobacterium avium or Cytomegalovirus.
  • Prior history of toxoplasmosis, Herpes simplex, Cryptococcus, or Pneumocystis carinii pneumonia (PCP) requiring chronic suppressive therapy.
  • Occasional premature atrial or ventricular contractions.
  • Prior Medication:
  • Required:
  • Zidovudine (AZT) therapy for at least 12 months, with a minimal daily dose of 500 mg/day, and with no more than 60 days off AZT therapy within the 12-month period (documentation of AZT dosing must be provided).
  • Allowed:
  • Intralesional agents.

Who cannot join

  • Co-existing Condition:
  • Patients with the following are excluded:
  • Psychological or emotional problems sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy.
  • AIDS-dementia complex = or > stage 2.
  • Active AIDS defining opportunistic infections not specifically allowed.
  • Intractable diarrhea.
Show all 41Show fewer
  • Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyperreflexia.
  • Prior history of acute pancreatitis within past 2 years or chronic pancreatitis.
  • History of seizures within past 2 years or currently requiring anticonvulsants for control.
  • History of past or current heart disease.
  • Malignancy likely in the investigator's opinion to require cytotoxic chemotherapy during the expected course of this trial.
  • Life expectancy < 3 months.
  • Concurrent Medication:
  • Excluded:
  • Isoniazid (INH). Neurotoxic drugs. Oral acidifying agents.
  • Patients with the following are excluded:
  • Psychological or emotional problems sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy.
  • AIDS-dementia complex = or > stage 2.
  • Active AIDS defining opportunistic infections not specifically allowed.
  • Intractable diarrhea.
  • Prior history of acute pancreatitis within past 2 years or chronic pancreatitis.
  • History of seizures within past 2 years or currently requiring anticonvulsants for control.
  • History of past or current heart disease.
  • Malignancy likely in the investigator's opinion to require cytotoxic chemotherapy during the expected course of this trial.
  • Life expectancy = or < 3 months.
  • Previous participation in any study of ddI, ddC or d4T.
  • Prior Medication:
  • Excluded:
  • Ganciclovir (DHPG).
  • Excluded within 1 month of study entry:
  • ddI and any other antiretroviral drug or investigational anti-HIV agent except for zidovudine (AZT).
  • Interferons.
  • Immunomodulating drugs.
  • Cytotoxic agents not specifically allowed.
  • Neurotoxic drugs.
  • Excluded within 3 months of study entry:
  • Ribavirin.
  • Prior Treatment:
  • Excluded within 14 days of study randomization:
  • Blood transfusion.
  • Active alcohol or drug abuse that is sufficient, in investigator's opinion, to prevent adequate compliance with study therapy.

Trial locations and contacts

71 sites in 2 countries.

71 sites in 2 countries

United States70 sites

  • Harvard (Massachusetts Gen Hosp)

    Boston, Massachusetts, 02114

  • Boston Med Ctr

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess - West Campus

    Boston, Massachusetts, 02215

  • Beth Israel Deaconess Med Ctr

    Boston, Massachusetts, 02215

  • SUNY / Erie County Med Ctr at Buffalo

    Buffalo, New York, 14215

  • Univ of North Carolina

    Chapel Hill, North Carolina, 275997215

  • Northwestern Univ Med School

    Chicago, Illinois, 60611

  • Rush Presbyterian - Saint Luke's Med Ctr

    Chicago, Illinois, 60612

  • Holmes Hosp / Univ of Cincinnati Med Ctr

    Cincinnati, Ohio, 452670405

  • Univ Hosp of Cleveland / Case Western Reserve Univ

    Cleveland, Ohio, 44106

  • Ohio State Univ Hosp Clinic

    Columbus, Ohio, 432101228

  • Mountain States Regional Hemophilia Ctr / Univ of Colorado

    Denver, Colorado, 80262

  • Univ of Colorado Health Sciences Ctr

    Denver, Colorado, 80262

  • Duke Univ Med Ctr

    Durham, North Carolina, 27710

  • City Hosp Ctr at Elmhurst / Mount Sinai Hosp

    Elmhurst, New York, 11373

  • G E Morey Jr

    Fort Lauderdale, Florida, 33316

  • Dr Stephen L Green

    Hampton, Virginia, 23666

  • Milton S Hershey Med Ctr

    Hershey, Pennsylvania, 170330850

  • Edward Hines Veterans Administration Hosp

    Hines, Illinois, 60141

  • Hermann Hosp / Univ Texas Health Science Ctr

    Houston, Texas, 77030

  • Indiana Univ Hosp

    Indianapolis, Indiana, 462025250

  • Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr

    Knoxville, Tennessee, 37920

  • Children's Hosp of Los Angeles/UCLA Med Ctr

    Los Angeles, California, 900276016

  • Los Angeles County - USC Med Ctr

    Los Angeles, California, 90033

  • Cedars Sinai / UCLA Med Ctr

    Los Angeles, California, 900481804

  • UCLA CARE Ctr

    Los Angeles, California, 90095

  • Harbor - UCLA Med Ctr / UCLA School of Medicine

    Los Angeles, California, 905022004

  • Univ of Miami School of Medicine

    Miami, Florida, 331361013

  • Dr Brian Buggy

    Milwaukee, Wisconsin, 53215

  • Milwaukee County Med Complex

    Milwaukee, Wisconsin, 53226

  • Great Lakes Hemophilia Foundation

    Milwaukee, Wisconsin, 53233

  • Univ of Minnesota

    Minneapolis, Minnesota, 55455

  • Louisiana Comprehensive Hemophilia Care Ctr

    New Orleans, Louisiana, 70112

  • Louisiana State Univ Med Ctr / Tulane Med School

    New Orleans, Louisiana, 70112

  • Tulane Univ School of Medicine

    New Orleans, Louisiana, 70112

  • Beth Israel Med Ctr / Peter Krueger Clinic

    New York, New York, 10003

  • Bellevue Hosp / New York Univ Med Ctr

    New York, New York, 10016

  • Cornell Univ Med Ctr

    New York, New York, 10021

  • Mem Sloan - Kettering Cancer Ctr

    New York, New York, 10021

  • Saint Luke's - Roosevelt Hosp Ctr

    New York, New York, 10025

  • Mount Sinai Hemophilia Ctr / Mount Sinai Med Ctr

    New York, New York, 10029

  • Mount Sinai Med Ctr

    New York, New York, 10029

  • Nebraska Regional Hemophilia Ctr

    Omaha, Nebraska, 68105

  • Palo Alto Veterans Adm Med Ctr / Stanford Univ

    Palo Alto, California, 94304

  • Univ of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Hemophilia Ctr of Western PA / Univ of Pittsburgh

    Pittsburgh, Pennsylvania, 15219

  • Univ of Pittsburgh Med School

    Pittsburgh, Pennsylvania

  • Univ of Rochester Medical Center

    Rochester, New York, 14642

  • Univ of California / San Diego Treatment Ctr

    San Diego, California, 921036325

  • San Francisco AIDS Clinic / San Francisco Gen Hosp

    San Francisco, California, 941102859

  • Stanford at Kaiser / Kaiser Permanente Med Ctr

    San Francisco, California, 94115

  • Univ of Washington

    Seattle, Washington, 98105

  • Baystate Med Ctr of Springfield

    Springfield, Massachusetts, 01199

  • Stanford Univ School of Medicine

    Stanford, California, 94305

  • SUNY - Stony Brook

    Stony Brook, New York, 117948153

  • Olive View Med Ctr

    Sylmar, California, 91342

  • Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr

    Sylmar, California, 91342

  • SUNY / State Univ of New York

    Syracuse, New York, 13210

  • Bronx Municipal Hosp Ctr/Jacobi Med Ctr

    The Bronx, New York, 10461

  • Jack Weiler Hosp / Bronx Municipal Hosp

    The Bronx, New York, 10465

  • Montefiore Med Ctr / Bronx Municipal Hosp

    The Bronx, New York, 10467

  • Bronx Veterans Administration / Mount Sinai Hosp

    The Bronx, New York, 10468

  • Med College of Ohio

    Toledo, Ohio, 43699

  • Harbor UCLA Med Ctr

    Torrance, California, 90502

  • George Washington Univ Med Ctr

    Washington D.C., District of Columbia, 20037

  • Julio Arroyo

    West Columbia, South Carolina, 29169

  • Univ of Kansas School of Medicine

    Wichita, Kansas, 67214

  • Bowman Gray School of Medicine / Wake Forest Univ

    Winston-Salem, North Carolina, 27103

  • Med Ctr of Central Massachusetts

    Worcester, Massachusetts, 01605

  • Univ of Massachusetts Med Ctr

    Worcester, Massachusetts, 01655

Other trials in United States

Puerto Rico1 site

  • San Juan Veterans Administration Med Ctr

    San Juan, 009275800

Other trials in Puerto Rico

About this study

To compare the effectiveness and toxicity of didanosine (ddI) and zidovudine (AZT) in patients with AIDS or advanced AIDS-related complex (ARC) who have tolerated AZT therapy for 12 months or longer. Per amendment, asymptomatic patients with CD4 counts less than 200 cells/mm3 are eligible.

AZT is effective in reducing mortality in patients with AIDS who receive the drug after the first episode of Pneumocystis carinii pneumonia (PCP) and in patients with advanced ARC. However, AZT therapy has been associated with significant toxicities. In addition, the effectiveness of AZT appears to decrease during the second and third years of therapy. For these reasons, the development of alternative therapy that would be at least as effective but less toxic is of great importance. The drug ddI is an antiviral agent that inhibits replication of HIV with less apparent toxicity than AZT. Studies indicate that ddI remains active in the body for at least 12 hours; thus benefits of ddI might be achieved with a low frequency of drug administration.

Read the detailed description

AZT is effective in reducing mortality in patients with AIDS who receive the drug after the first episode of Pneumocystis carinii pneumonia (PCP) and in patients with advanced ARC. However, AZT therapy has been associated with significant toxicities. In addition, the effectiveness of AZT appears to decrease during the second and third years of therapy. For these reasons, the development of alternative therapy that would be at least as effective but less toxic is of great importance. The drug ddI is an antiviral agent that inhibits replication of HIV with less apparent toxicity than AZT. Studies indicate that ddI remains active in the body for at least 12 hours; thus benefits of ddI might be achieved with a low frequency of drug administration.

Two dose levels of ddI, each adjusted depending on patient's weight at study entry, are compared with a variable dosage regimen of AZT (the dose which the patient is tolerating at the time of study entry). Randomization is stratified by baseline CD4 cell count (less than 100 or 100-300) and Medical Center. This study continues for at least 12 months after the entry of the first subject. Patients randomized to AZT will receive orally. All patients randomized to AZT also receive a ddI placebo at 12 hour intervals. Patients randomized to ddI receive AZT placebo.

Conditions
HIV Infections
Being tested
Zidovudine, Didanosine
Keywords
Didanosine, Zidovudine
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Primary completionMar 1992

Resources

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
Masking
Double blind
Enrolment
750 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000671
Sponsor's protocol ID
ACTG 117
Other IDs
070V1, AI454-009
Status last verified
Aug 1992
First submitted
2 Nov 1999
Last updated
14 Mar 2011
Results posted
No

Publications

  • Smith MS, Koerber KL, Pagano JS. Long-term persistence of zidovudine resistance mutations in plasma isolates of human immunodeficiency virus type 1 of dideoxyinosine-treated patients removed from zidovudine therapy. J Infect Dis. 1994 Jan;169(1):184-8. doi: 10.1093/infdis/169.1.184.

    PubMed 7506280

  • Bozzette SA, Hays RD, Berry SH, Kanouse DE. A Perceived Health Index for use in persons with advanced HIV disease: derivation, reliability, and validity. Med Care. 1994 Jul;32(7):716-31. doi: 10.1097/00005650-199407000-00005.

    PubMed 8028406

  • Fiscus SA, Heggem-Snow A, Troiani L, Wallmark E, Folds JD, Sheff B, van der Horst CM. Transient high titers of HIV-1 in plasma and progression of disease. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 May 1;9(1):51-7.

    PubMed 7712235

  • Coombs RW, Welles SL, Hooper C, Reichelderfer PS, D'Aquila RT, Japour AJ, Johnson VA, Kuritzkes DR, Richman DD, Kwok S, Todd J, Jackson JB, DeGruttola V, Crumpacker CS, Kahn J. Association of plasma human immunodeficiency virus type 1 RNA level with risk of clinical progression in patients with advanced infection. AIDS Clinical Trials Group (ACTG) 116B/117 Study Team. ACTG Virology Committee Resistance and HIV-1 RNA Working Groups. J Infect Dis. 1996 Oct;174(4):704-12. doi: 10.1093/infdis/174.4.704.

    PubMed 8843206

  • Richardson D, Liou SH, Kahn JO. Uric acid and didanosine compliance in AIDS clinical trials: an analysis of AIDS Clinical Trials Group protocols 116A and 116B/117. J Acquir Immune Defic Syndr (1988). 1993 Nov;6(11):1212-23.

    PubMed 8229656

  • Kozal M, Winters M, Shafer R, Kroodsma K, Katzenstein D, Merigan T. Behavior of codon 74 and 215 pol gene mutations in 62 AZT experienced patients on ddI monotherapy. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;55

  • Kozal MJ, Kroodsma K, Winters MA, Shafer RW, Efron B, Katzenstein DA, Merigan TC. Didanosine resistance in HIV-infected patients switched from zidovudine to didanosine monotherapy. Ann Intern Med. 1994 Aug 15;121(4):263-8. doi: 10.7326/0003-4819-121-4-199408150-00005.

    PubMed 7518658

  • Schooley RT. Correlation between viral load measurements and outcome in clinical trials of antiviral drugs. AIDS. 1995 Dec;9 Suppl 2:S15-S19.

    PubMed 8775802

  • Kahn JO, Lagakos SW, Richman DD, Cross A, Pettinelli C, Liou SH, Brown M, Volberding PA, Crumpacker CS, Beall G, et al. A controlled trial comparing continued zidovudine with didanosine in human immunodeficiency virus infection. The NIAID AIDS Clinical Trials Group. N Engl J Med. 1992 Aug 27;327(9):581-7. doi: 10.1056/NEJM199208273270901.

    PubMed 1353607

  • Richman DD. Clinical significance of drug resistance in human immunodeficiency virus. Clin Infect Dis. 1995 Oct;21 Suppl 2:S166-9. doi: 10.1093/clinids/21.supplement_2.s166.

    PubMed 8845446

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zidovudine and Didanosine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 71 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 26 inclusion and 41 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 14 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 71 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 NCT00000671, which also lists 10 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 14 Mar 2011.

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