AzTrials
AzTrials

HIV InfectionsPhase 2NCT00000672

An Efficacy Study of 2',3'-Dideoxyinosine (ddI) (BMY-40900) Administered Orally Twice Daily to Zidovudine Intolerant Patients With AIDS or AIDS-Related Complex

A Phase 2 study testing Didanosine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 67 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

AMENDED: 8/29/90 Inclusion of asymptomatic patients with CD4 counts less than 200 cells/mm3. Standardization of baseline evaluation schedule to allow 14 days prior to study dosing. Reduction in frequency and intensity of follow-up evaluations. Standardization of study endpoints. 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?
Didanosine
How many people
660 participants
Where
67 sitesin 2 countries
Study dates
Start not givento Feb 1993
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). In the event of physiological intolerance, alternative PCP prophylaxis may be trimethoprim/sulfamethoxazole 1 DS tab per day or dapsone 50 - 100 mg per day.
  • Allowed:
  • Chronic suppressive treatment for toxoplasmosis, Pneumocystis carinii pneumonia (PCP), cryptococcal meningitis, herpes simplex virus, cytomegalovirus, coccidioidomycosis, and histoplasmosis (absorption of ketoconazole or dapsone may be inhibited if given at the same time as the buffered solution of ddI, and should be taken 2 hours before or 2 hours after taking ddI; oral acidifying agents are not allowed). Isoniazid is permitted only if no acceptable alternative therapy is available. Metronidazole may be used for single courses not to exceed 14 days within consecutive 90 day intervals, the first of which begins at the initiation of the study. Erythropoietin for patients under the relevant treatment IND. Intravenous acyclovir for short courses of therapy.
  • Patients must:
Show all 20Show fewer
  • Have documented hematologic intolerance to zidovudine (AZT).
  • Have the diagnosis of AIDS or advanced AIDS related complex (ARC).
  • Have ended treatment for acute Pneumocystis carinii pneumonia (PCP) at least 2 weeks before study entry.
  • Have previous intolerance on at least two courses of AZT therapy (one of which must have been at daily doses of 500 mg of AZT or less).
  • Be able to provide informed consent (and/or guardian as appropriate).
  • Be available for follow-up for at least 6 months.
  • Have baseline laboratory values as measured within 7 days before initial drug dosing.
  • Allowed:
  • Development of new opportunistic infections during the study - patients remain in the protocol.
  • Prior Medication:
  • Required:
  • Prior use and intolerance to zidovudine (AZT).
  • Allowed:
  • Intralesional agents.

Who cannot join

  • Co-existing Condition:
  • Patients with the following are excluded:
  • Presence of Kaposi's sarcoma (KS) with known or suspected visceral disease or where KS requires chemotherapy.
  • Active AIDS defining opportunistic infections not specifically allowed.
  • Intractable diarrhea.
  • Stage 2 AIDS-dementia complex.
Show all 43Show fewer
  • History of intolerance to aerosolized pentamidine.
  • 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 hyporeflexia.
  • Prior history of acute or chronic pancreatitis.
  • History of seizures within past 2 years or currently requiring anticonvulsants for control.
  • Any other clinical conditions or prior therapy which, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.
  • Concurrent Medication:
  • Excluded:
  • Isoniazid (INH).
  • Patients with the following are excluded:
  • Active AIDS-defining opportunistic infections not specifically allowed.
  • Intractable diarrhea.
  • AIDS-dementia complex = or > stage 2.
  • History of intolerance to aerosolized pentamidine. 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 hyporeflexia.
  • Prior history of acute or chronic pancreatitis.
  • History of seizures within past 2 years or currently requiring anticonvulsants for control.
  • Any other clinical conditions or prior therapy which, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.
  • Previous participation in any Phase I ddI study.
  • Life expectancy < 6 months.
  • Prior Medication:
  • Excluded:
  • Chronic therapy for cytomegalovirus infection with ganciclovir.
  • ddI.
  • d4T.
  • ddC.
  • Excluded within 2 weeks of study entry:
  • Zidovudine (AZT).
  • Excluded within 1 month of study entry:
  • Therapy with any other antiretroviral drug or investigational agent not specifically allowed, including interferon and immunomodulating drugs.
  • Ganciclovir.
  • Neurotoxic drugs.
  • Excluded within 3 months of study entry:
  • Ribavirin.
  • Cytotoxic anticancer therapy.
  • Prior Treatment:
  • Excluded within 2 weeks of study randomization:
  • Transfusion.
  • Active alcohol or drug abuse that is sufficient, in investigator's opinion, to prevent adequate compliance with study therapy.

Trial locations and contacts

67 sites in 2 countries.

67 sites in 2 countries

United States66 sites

  • Johns Hopkins Hosp

    Baltimore, Maryland, 21287

  • 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

  • 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

  • Univ TX Galveston Med Branch

    Galveston, Texas, 77550

  • 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

  • Texas Children's Hosp / Baylor Univ

    Houston, Texas, 77030

  • Indiana Univ Hosp

    Indianapolis, Indiana, 462025250

  • Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr

    Knoxville, Tennessee, 37920

  • Los Angeles County - USC Med Ctr

    Los Angeles, California, 90033

  • Cedars Sinai / UCLA Med Ctr

    Los Angeles, California, 900481804

  • UCLA Med Ctr / Pediatric

    Los Angeles, California, 900951752

  • Harbor - UCLA Med Ctr / UCLA School of Medicine

    Los Angeles, California, 905022004

  • Univ of Miami School of Medicine

    Miami, Florida, 331361013

  • 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

  • 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 Utah School of Medicine

    Salt Lake City, Utah, 84132

  • Univ of California / San Diego Treatment Ctr

    San Diego, California, 921036325

  • 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

  • Univ of South Florida

    Tampa, Florida, 33612

  • 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

  • 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

AMENDED: 8/29/90 Inclusion of asymptomatic patients with CD4 counts less than 200 cells/mm3. Standardization of baseline evaluation schedule to allow 14 days prior to study dosing. Reduction in frequency and intensity of follow-up evaluations. Standardization of study endpoints. Inclusion of toxicity scoring and management for amylase and triglyceride elevations. Clarification of concomitant medication use. Original design: To determine the effectiveness of didanosine (ddI) in patients with AIDS or advanced AIDS related complex (ARC) who have documented hematologic intolerance to zidovudine (AZT) therapy. To determine if the efficacy of ddI increases with increasing doses.

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. The major dose-limiting toxicities found in the Phase I studies have been pains in the feet and legs of 2 patients initially receiving 12 mg/kg/day and 12 patients receiving daily doses of 25.8 to 51.2 mg/kg; symptoms began 8 to 27 weeks after initiating ddI treatment. These neuropathy-like symptoms have generally not been associated with significant abnormalities in nerve conduction studies and patients have reported marked improvement in symptoms within 1 to 2 weeks of discontinuing ddI. Some patients have resumed ddI treatment at a reduced dose after resolution of their symptoms. Studies indicate that ddI remains active in the body for at least 12 hours. This indicates that 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 (reproduction) of HIV with less apparent toxicity than AZT. The major dose-limiting toxicities found in the Phase I studies have been pains in the feet and legs of 2 patients initially receiving 12 mg/kg/day and 12 patients receiving daily doses of 25.8 to 51.2 mg/kg; symptoms began 8 to 27 weeks after initiating ddI treatment. These neuropathy-like symptoms have generally not been associated with significant abnormalities in nerve conduction studies and patients have reported marked improvement in symptoms within 1 to 2 weeks of discontinuing ddI. Some patients have resumed ddI treatment at a reduced dose after resolution of their symptoms. Studies indicate that ddI remains active in the body for at least 12 hours. This indicates that benefits of ddI might be achieved with a low frequency of drug administration.

Patients are randomized to one of three ddI treatment groups; within each group, doses will be adjusted according to patient's weight at study entry. Stratification is by diagnosis of AIDS or AIDS related complex (ARC) and Medical Center. Data will be tabulated for the Data and Safety Monitoring Board at 3 month intervals.

Conditions
HIV Infections
Being tested
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.

  • DidanosineDrug

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 completionFeb 1993

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
Enrolment
660 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000672
Sponsor's protocol ID
ACTG 118
Other IDs
070V1, AI454-007
Status last verified
Oct 1994
First submitted
2 Nov 1999
Last updated
14 Mar 2011
Results posted
No

Publications

  • 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.

    PubMed 7552481

  • 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

  • Reddy MM, Winger EE, Hargrove D, McHugh T, McKinley GF, Grieco MH. An improved method for monitoring efficacy of anti-retroviral therapy in HIV-infected individuals: a highly sensitive HIV p24 antigen assay. J Clin Lab Anal. 1992;6(3):125-9. doi: 10.1002/jcla.1860060305.

    PubMed 1506978

  • Grieco MH, McKinley GF, Reddy MM. Effect of 2',3',-dideoxyinosine on HIV P24 antigen, beta2-microglobulin, neopterin,SCD8,SCD4,and SIL2R levels in patients with ARC or AIDS. Int Conf AIDS. 1991 Jun 16-21;7(2):199 (abstract no WB2069)

  • 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

  • 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.

    PubMed 9342254

  • Allan JD, DeGruttola V, Cross A, McLaren C, Seidlin M, Pettinelli C. An efficacy study of 2'3'-dideoxyinosine [ddI](BMY-40900) administered orally twice daily to zidovudine intolerant patients with HIV infection (ACTG 118). The AIDS Clinical Trials Group. Int Conf AIDS. 1993 Jun 6-11;9(1):67 (abstract no WS-B24-2)

  • Sharma PL, Chatis PA, Dogon AL, Mayers DL, McCutchan FE, Page C, Crumpacker CS. AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay. Virology. 1996 Sep 15;223(2):365-9. doi: 10.1006/viro.1996.0488.

    PubMed 8806572

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Didanosine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 67 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 20 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 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 67 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 NCT00000672, which also lists 9 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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