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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


Phase 2
12 Years
N/A
Not Enrolling
Both
HIV Infections

Thank you

Trial Information

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


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.

Inclusion Criteria


Inclusion Criteria

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.

- 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.

Exclusion Criteria

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.

- 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.

Type of Study:

Interventional

Study Design:

Masking: Double-Blind, Primary Purpose: Treatment

Principal Investigator

J Kahn

Investigator Role:

Study Chair

Authority:

United States: Federal Government

Study ID:

ACTG 117

NCT ID:

NCT00000671

Start Date:

Completion Date:

Related Keywords:

  • HIV Infections
  • Didanosine
  • Zidovudine
  • HIV Infections
  • Acquired Immunodeficiency Syndrome

Name

Location

Children's Hosp of Los Angeles/UCLA Med CtrLos Angeles, California  900276016
Bellevue Hosp / New York Univ Med CtrNew York, New York  10016
Mem Sloan - Kettering Cancer CtrNew York, New York  10021
Saint Luke's - Roosevelt Hosp CtrNew York, New York  10025
Univ of Rochester Medical CenterRochester, New York  14642
Julio ArroyoWest Columbia, South Carolina  29169
Los Angeles County - USC Med CtrLos Angeles, California  90033
Cedars Sinai / UCLA Med CtrLos Angeles, California  900481804
UCLA CARE CtrLos Angeles, California  90095
Harbor - UCLA Med Ctr / UCLA School of MedicineLos Angeles, California  905022004
Palo Alto Veterans Adm Med Ctr / Stanford UnivPalo Alto, California  94304
Univ of California / San Diego Treatment CtrSan Diego, California  921036325
San Francisco AIDS Clinic / San Francisco Gen HospSan Francisco, California  941102859
Stanford at Kaiser / Kaiser Permanente Med CtrSan Francisco, California  94115
Stanford Univ School of MedicineStanford, California  94305
Sepulveda Veterans Adm Med Ctr / Olive View Med CtrSylmar, California  91342
Olive View Med CtrSylmar, California  91342
Harbor UCLA Med CtrTorrance, California  90502
Univ of Colorado Health Sciences CtrDenver, Colorado  80262
Mountain States Regional Hemophilia Ctr / Univ of ColoradoDenver, Colorado  80262
George Washington Univ Med CtrWashington, District of Columbia  20037
G E Morey JrFort Lauderdale, Florida  33316
Univ of Miami School of MedicineMiami, Florida  331361013
Rush Presbyterian - Saint Luke's Med CtrChicago, Illinois  60612
Northwestern Univ Med SchoolChicago, Illinois  60611
Edward Hines Veterans Administration HospHines, Illinois  60141
Indiana Univ HospIndianapolis, Indiana  462025250
Univ of Kansas School of MedicineWichita, Kansas  67214
Louisiana State Univ Med Ctr / Tulane Med SchoolNew Orleans, Louisiana  70112
Tulane Univ School of MedicineNew Orleans, Louisiana  70112
Louisiana Comprehensive Hemophilia Care CtrNew Orleans, Louisiana  70112
Harvard (Massachusetts Gen Hosp)Boston, Massachusetts  02114
Beth Israel Deaconess Med CtrBoston, Massachusetts  02215
Beth Israel Deaconess - West CampusBoston, Massachusetts  02215
Boston Med CtrBoston, Massachusetts  02118
Baystate Med Ctr of SpringfieldSpringfield, Massachusetts  01199
Univ of Massachusetts Med CtrWorcester, Massachusetts  01655
Med Ctr of Central MassachusettsWorcester, Massachusetts  01605
Univ of MinnesotaMinneapolis, Minnesota  55455
Nebraska Regional Hemophilia CtrOmaha, Nebraska  68105
Bronx Municipal Hosp Ctr/Jacobi Med CtrBronx, New York  10461
Jack Weiler Hosp / Bronx Municipal HospBronx, New York  10465
Bronx Veterans Administration / Mount Sinai HospBronx, New York  10468
Montefiore Med Ctr / Bronx Municipal HospBronx, New York  10467
SUNY / Erie County Med Ctr at BuffaloBuffalo, New York  14215
City Hosp Ctr at Elmhurst / Mount Sinai HospElmhurst, New York  11373
Mount Sinai Hemophilia Ctr / Mount Sinai Med CtrNew York, New York  10029
Cornell Univ Med CtrNew York, New York  10021
Mount Sinai Med CtrNew York, New York  10029
Beth Israel Med Ctr / Peter Krueger ClinicNew York, New York  10003
SUNY - Stony BrookStony Brook, New York  117948153
SUNY / State Univ of New YorkSyracuse, New York  13210
Univ of North CarolinaChapel Hill, North Carolina  275997215
Duke Univ Med CtrDurham, North Carolina  27710
Bowman Gray School of Medicine / Wake Forest UnivWinston-Salem, North Carolina  27103
Holmes Hosp / Univ of Cincinnati Med CtrCincinnati, Ohio  452670405
Univ Hosp of Cleveland / Case Western Reserve UnivCleveland, Ohio  44106
Ohio State Univ Hosp ClinicColumbus, Ohio  432101228
Med College of OhioToledo, Ohio  43699
Milton S Hershey Med CtrHershey, Pennsylvania  170330850
Univ of PennsylvaniaPhiladelphia, Pennsylvania  19104
Hemophilia Ctr of Western PA / Univ of PittsburghPittsburgh, Pennsylvania  15219
Univ of Pittsburgh Med SchoolPittsburgh, Pennsylvania  
Univ of Tennessee / E Tennessee Comprehensive Hemophilia CtrKnoxville, Tennessee  37920
Hermann Hosp / Univ Texas Health Science CtrHouston, Texas  77030
Dr Stephen L GreenHampton, Virginia  23666
Univ of WashingtonSeattle, Washington  98105
Great Lakes Hemophilia FoundationMilwaukee, Wisconsin  53233
Dr Brian BuggyMilwaukee, Wisconsin  53215
Milwaukee County Med ComplexMilwaukee, Wisconsin  53226