NCT00000979

Brief Summary

To compare the effectiveness and toxicity of didanosine (ddI) and zidovudine (AZT) in patients with AIDS, advanced AIDS-related complex (ARC), or asymptomatic infection with CD4 counts \< 200 cells/mm3. 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 (reproduction) of HIV with less apparent toxicity than AZT.

Trial Health

85
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,500

participants targeted

Target at P75+ for phase_2 hiv-infections

Geographic Reach
2 countries

71 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Primary Completion

Last participant's last visit for primary outcome

October 1, 1992

Completed
7.1 years until next milestone

First Submitted

Initial submission to the registry

November 2, 1999

Completed
1.8 years until next milestone

First Posted

Study publicly available on registry

August 31, 2001

Completed
Last Updated

March 14, 2011

Status Verified

January 1, 2003

First QC Date

November 2, 1999

Last Update Submit

March 11, 2011

Conditions

Keywords

DidanosineZidovudine

Interventions

Eligibility Criteria

Age12 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Concurrent Medication:
  • Required:
  • Aerosolized pentamidine (300 mg every 4 weeks using a Respirgard II nebulizer). In the event of physiological intolerance, alternative prophylaxis may be: Trimethoprim / sulfamethoxazole 1 DS tab per day or dapsone 50 - 100 mg/day.
  • Allowed:
  • Maintenance therapy for active AIDS defining opportunistic infections for patients with 9 to 47 weeks' experience with zidovudine (AZT).
  • Treatment of opportunistic infections with other than sulfonamide containing drugs:
  • Pyrimethamine and sulfadiazine or clindamycin for suppression of toxoplasmosis acquired after study entry; fluconazole or amphotericin B for suppression of cryptococcosis or ketoconazole for candidiasis.
  • Intravenous acyclovir for up to 10 days. Erythropoietin for patients under the relevant treatment IND. Analgesics, antihistamines, antiemetics, antidiarrheal agents for symptomatic therapy for toxicities.
  • Isoniazid (INH) if no other acceptable therapy is available.
  • Metronidazole may be used for single courses of therapy not to exceed 14 days within consecutive 90 day intervals. Note:
  • Ketoconazole and dapsone should be taken 2 hours before or 2 hours after taking ddI (amendment 5/20/91).
  • Concurrent Treatment:
  • Allowed:
  • Blood transfusions for hemoglobin toxicity.
  • Patients must:
  • +13 more criteria

You may not qualify if:

  • Co-existing Condition:
  • Patients with the following symptoms or diseases are excluded:
  • Kaposi's sarcoma (KS) with evidence of visceral disease or where KS requires chemotherapy; subjects with localized KS having CD4 counts = or \> 200 cells/mm3.
  • AIDS-dementia complex = or \> stage 2.
  • Prior history of acute pancreatitis within past 2 years or chronic pancreatitis.
  • Intractable diarrhea.
  • History of seizures within past 6 months or currently requiring anticonvulsants for control.
  • History of past or current heart disease.
  • Presence of a malignancy likely in the investigators opinion to require cytotoxic myelosuppressive chemotherapy during the expected course of this trial.
  • Concurrent Medication:
  • Excluded:
  • Oral acidifying agents.
  • Neurotoxic drugs. NOTE: If patients require therapy for PCP with IV pentamidine, study mediation is stopped.
  • Patients with the following are excluded:
  • Active AIDS defining events. Maintenance therapy for prior AIDS-defining opportunistic infections is permitted.
  • +25 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (71)

Children's Hosp of Los Angeles/UCLA Med Ctr

Los Angeles, California, 900276016, United States

Location

Los Angeles County - USC Med Ctr

Los Angeles, California, 90033, United States

Location

Palo Alto Veterans Adm Med Ctr / Stanford Univ

Palo Alto, California, 94304, United States

Location

Univ of California / San Diego Treatment Ctr

San Diego, California, 921036325, United States

Location

Stanford Univ School of Medicine

Stanford, California, 94305, United States

Location

Olive View Med Ctr

Sylmar, California, 91342, United States

Location

Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr

Sylmar, California, 91342, United States

Location

Harbor UCLA Med Ctr

Torrance, California, 90502, United States

Location

Mountain States Regional Hemophilia Ctr / Univ of Colorado

Denver, Colorado, 80262, United States

Location

Univ of Colorado Health Sciences Ctr

Denver, Colorado, 80262, United States

Location

Whitman - Walker Clinic

Washington D.C., District of Columbia, 20009, United States

Location

George Washington Univ Med Ctr

Washington D.C., District of Columbia, 20037, United States

Location

G E Morey Jr

Fort Lauderdale, Florida, 33316, United States

Location

Univ of Miami School of Medicine

Miami, Florida, 331361013, United States

Location

Northwestern Univ Med School

Chicago, Illinois, 60611, United States

Location

Cook County Hosp

Chicago, Illinois, 60612, United States

Location

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, 60612, United States

Location

Edward Hines Veterans Administration Hosp

Hines, Illinois, 60141, United States

Location

Indiana Univ Hosp

Indianapolis, Indiana, 462025250, United States

Location

Univ of Kansas School of Medicine

Wichita, Kansas, 67214, United States

Location

Charity Hosp / Tulane Univ Med School

New Orleans, Louisiana, 70112, United States

Location

Louisiana Comprehensive Hemophilia Care Ctr

New Orleans, Louisiana, 70112, United States

Location

Louisiana State Univ Med Ctr / Tulane Med School

New Orleans, Louisiana, 70112, United States

Location

Tulane Univ School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins Hosp

Baltimore, Maryland, 21287, United States

Location

Harvard (Massachusetts Gen Hosp)

Boston, Massachusetts, 02114, United States

Location

Boston Med Ctr

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess - West Campus

Boston, Massachusetts, 02215, United States

Location

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

Location

Baystate Med Ctr of Springfield

Springfield, Massachusetts, 01199, United States

Location

Med Ctr of Central Massachusetts

Worcester, Massachusetts, 01605, United States

Location

Univ of Massachusetts Med Ctr

Worcester, Massachusetts, 01655, United States

Location

Univ of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Nebraska Regional Hemophilia Ctr

Omaha, Nebraska, 68105, United States

Location

SUNY / Erie County Med Ctr at Buffalo

Buffalo, New York, 14215, United States

Location

City Hosp Ctr at Elmhurst / Mount Sinai Hosp

Elmhurst, New York, 11373, United States

Location

Beth Israel Med Ctr / Peter Krueger Clinic

New York, New York, 10003, United States

Location

Bellevue Hosp / New York Univ Med Ctr

New York, New York, 10016, United States

Location

Cornell Univ Med Ctr

New York, New York, 10021, United States

Location

Mem Sloan - Kettering Cancer Ctr

New York, New York, 10021, United States

Location

Saint Luke's - Roosevelt Hosp Ctr

New York, New York, 10025, United States

Location

Mount Sinai Med Ctr

New York, New York, 10029, United States

Location

Univ of Rochester Medical Center

Rochester, New York, 14642, United States

Location

SUNY - Stony Brook

Stony Brook, New York, 117948153, United States

Location

SUNY / State Univ of New York

Syracuse, New York, 13210, United States

Location

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

The Bronx, New York, 10461, United States

Location

Jack Weiler Hosp / Bronx Municipal Hosp

The Bronx, New York, 10465, United States

Location

Montefiore Med Ctr / Bronx Municipal Hosp

The Bronx, New York, 10467, United States

Location

Bronx Veterans Administration / Mount Sinai Hosp

The Bronx, New York, 10468, United States

Location

Univ of North Carolina

Chapel Hill, North Carolina, 275997215, United States

Location

Duke Univ Med Ctr

Durham, North Carolina, 27710, United States

Location

Bowman Gray School of Medicine / Wake Forest Univ

Winston-Salem, North Carolina, 27103, United States

Location

Holmes Hosp / Univ of Cincinnati Med Ctr

Cincinnati, Ohio, 452670405, United States

Location

Ohio State Univ Hosp Clinic

Columbus, Ohio, 432101228, United States

Location

Med College of Ohio

Toledo, Ohio, 43699, United States

Location

Milton S Hershey Med Ctr

Hershey, Pennsylvania, 170330850, United States

Location

Univ of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Hemophilia Ctr of Western PA / Univ of Pittsburgh

Pittsburgh, Pennsylvania, 15219, United States

Location

Univ of Pittsburgh Med School

Pittsburgh, Pennsylvania, United States

Location

Julio Arroyo

West Columbia, South Carolina, 29169, United States

Location

Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr

Knoxville, Tennessee, 37920, United States

Location

Univ TX Galveston Med Branch

Galveston, Texas, 77550, United States

Location

Hermann Hosp / Univ Texas Health Science Ctr

Houston, Texas, 77030, United States

Location

Texas Children's Hosp / Baylor Univ

Houston, Texas, 77030, United States

Location

Univ of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

Dr Stephen L Green

Hampton, Virginia, 23666, United States

Location

Univ of Washington

Seattle, Washington, 98105, United States

Location

Dr Brian Buggy

Milwaukee, Wisconsin, 53215, United States

Location

Milwaukee County Med Complex

Milwaukee, Wisconsin, 53226, United States

Location

Great Lakes Hemophilia Foundation

Milwaukee, Wisconsin, 53233, United States

Location

San Juan Veterans Administration Med Ctr

San Juan, 009275800, Puerto Rico

Location

Related Publications (11)

  • Dolin R, Amato DA, Fischl MA, Pettinelli C, Beltangady M, Liou SH, Brown MJ, Cross AP, Hirsch MS, Hardy WD, et al. Zidovudine compared with didanosine in patients with advanced HIV type 1 infection and little or no previous experience with zidovudine. AIDS Clinical Trials Group. Arch Intern Med. 1995 May 8;155(9):961-74.

    PMID: 7726705BACKGROUND
  • 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.

    PMID: 8028406BACKGROUND
  • 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.

    PMID: 7712235BACKGROUND
  • Schooley RT. Correlation between viral load measurements and outcome in clinical trials of antiviral drugs. AIDS. 1995 Dec;9 Suppl 2:S15-S19.

    PMID: 8775802BACKGROUND
  • 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.

    PMID: 7518658BACKGROUND
  • Fichtenbaum CJ, Clifford DB, Powderly WG. Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):169-74. doi: 10.1097/00042560-199510020-00009.

    PMID: 7552481BACKGROUND
  • Spino C, Kahn JO, Dolin R, Phair JP. Predictors of survival in HIV-infected persons with 50 or fewer CD4 cells/mm3. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Aug 15;15(5):346-55. doi: 10.1097/00042560-199708150-00004.

    PMID: 9342254BACKGROUND
  • 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.

  • Welles SL, Jackson JB, Yen-Lieberman B, Demeter L, Japour AJ, Smeaton LM, Johnson VA, Kuritzkes DR, D'Aquila RT, Reichelderfer PA, Richman DD, Reichman R, Fischl M, Dolin R, Coombs RW, Kahn JO, McLaren C, Todd J, Kwok S, Crumpacker CS. Prognostic value of plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in patients with advanced HIV-1 disease and with little or no prior zidovudine therapy. AIDS Clinical Trials Group Protocol 116A/116B/117 Team. J Infect Dis. 1996 Oct;174(4):696-703. doi: 10.1093/infdis/174.4.696.

  • 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.

  • Mildvan D, Spritzler J, Grossberg SE, Fahey JL, Johnston DM, Schock BR, Kagan J. Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection. Clin Infect Dis. 2005 Mar 15;40(6):853-8. doi: 10.1086/427877. Epub 2005 Feb 18.

MeSH Terms

Conditions

HIV Infections

Interventions

ZidovudineDidanosine

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

ThymidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDideoxynucleosidesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesInosinePurine NucleosidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingRibonucleosides

Study Officials

  • R Dolin

    STUDY CHAIR
  • M Fischl

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Purpose
TREATMENT
Sponsor Type
NIH

Study Record Dates

First Submitted

November 2, 1999

First Posted

August 31, 2001

Primary Completion

October 1, 1992

Last Updated

March 14, 2011

Record last verified: 2003-01

Locations