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A Prospective, Randomized, Open-Label, Comparative Trial of Dideoxyinosine (ddI) Versus Dideoxycytidine (ddC) in HIV-Infected Patients Who Are Intolerant of or Who Have Failed Zidovudine (AZT) Therapy

Primary Purpose

HIV Infections

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Zalcitabine
Didanosine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Zalcitabine, Didanosine, Drug Evaluation, Zidovudine

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Acyclovir (if patient is also receiving ddC, clinical monitoring should be more frequent). Analgesics, antiemetics, antidiarrheal agents, or other necessary treatment for symptomatic therapy. Interferons for maintenance therapy of Kaposi's sarcoma. GM-CSF. Required: Prophylaxis against Pneumocystis carinii pneumonia (PCP) if their absolute CD4+ lymphocyte count is < 200 cells/mm3 at study entry. PCP prophylaxis for patient with CD4+ counts between 200 and 300 cells/mm3 is at discretion of patient's primary physician. NOTE: There is potential interaction of ddI and dapsone. Concurrent Treatment: Allowed: Transfusion, erythropoietin. Patients must have the following: Zidovudine (AZT) failure after having received a cumulative duration of at least 6 months. AZT intolerance - rechallenge is not required for patients exhibiting = or > grade III cutaneous symptoms. Diagnosis of AIDS or CD4+ = or < 300 cells/mm3 OR AIDS-defining illness other than Kaposi's sarcoma. Willingness and ability to comply with protocol. Informed consent must be obtained for all study participants in accordance with state law, local IRB requirements, and 45 CFR Part 46. AMENDED 11/19/90 to include assent by minors if they are physically able, in addition to consent by parents. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Any disorders for which the study drugs are contraindicated (didanosine (ddI)) is contraindicated in renal impairment, heart disease, receiving renal dialysis. Active opportunistic infection. Concurrent Medication: Excluded: Other antiretroviral agents. Use of drugs associated with peripheral neuropathy or use of agents that may cause pancreatitis including intravenous pentamidine and alcohol should be restricted or avoided. Concurrent Treatment: Excluded: Other concurrent antiretroviral clinical trials. Patients with the following are excluded: History of pancreatitis, peripheral neuropathy, uncontrolled seizures, renal impairment, heart disease, stage 2 or higher ADC. Any other disorders for which the study drugs are contraindicated, i.e., ddI is contraindicated in renal impairment, patients receiving renal dialysis, and heart disease. Receiving acute therapy for active AIDS defining opportunistic infection on enrollment. Prior Medication: Excluded: Didanosine (ddI). Dideoxycytidine (ddC) . Excessive alcohol use that, in investigator's opinion, puts patient at risk of developing pancreatic disease.

Sites / Locations

  • Community Consortium of San Francisco
  • Denver CPCRA / Denver Public Hlth
  • Hill Health Corp
  • Wilmington Hosp / Med Ctr of Delaware
  • Veterans Administration Med Ctr / Regional AIDS Program
  • AIDS Research Consortium of Atlanta
  • AIDS Research Alliance - Chicago
  • Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
  • Comprehensive AIDS Alliance of Detroit
  • Henry Ford Hosp
  • North Jersey Community Research Initiative
  • Bronx Lebanon Hosp Ctr
  • Clinical Directors Network of Region II
  • Harlem AIDS Treatment Group / Harlem Hosp Ctr
  • Portland Veterans Adm Med Ctr / Rsch & Education Grp
  • Richmond AIDS Consortium

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00000969
Brief Title
A Prospective, Randomized, Open-Label, Comparative Trial of Dideoxyinosine (ddI) Versus Dideoxycytidine (ddC) in HIV-Infected Patients Who Are Intolerant of or Who Have Failed Zidovudine (AZT) Therapy
Official Title
A Prospective, Randomized, Open-Label, Comparative Trial of Dideoxyinosine (ddI) Versus Dideoxycytidine (ddC) in HIV-Infected Patients Who Are Intolerant of or Who Have Failed Zidovudine (AZT) Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
September 1992 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
To evaluate and compare the effectiveness and toxicity associated with didanosine ( ddI ) and zalcitabine ( dideoxycytidine; ddC ) in patients with HIV infection who are intolerant of or have failed zidovudine ( AZT ) therapy. Alternative and less toxic treatments need to be investigated for the treatment of HIV infection. Studies have shown that the dideoxynucleosides ddI and ddC may be effective antiretroviral agents in the treatment of HIV-infected individuals. However, ddI and ddC have yet to be compared on the basis of patient survival, drug tolerance, immunologic and virologic effectiveness, and the incidence of opportunistic infection or opportunistic malignancy. Results of this study will yield information regarding the relative therapeutic benefits and toxicities of each drug while providing alternative treatment to patients who are unable to tolerate or have had progression of disease while on AZT.
Detailed Description
Alternative and less toxic treatments need to be investigated for the treatment of HIV infection. Studies have shown that the dideoxynucleosides ddI and ddC may be effective antiretroviral agents in the treatment of HIV-infected individuals. However, ddI and ddC have yet to be compared on the basis of patient survival, drug tolerance, immunologic and virologic effectiveness, and the incidence of opportunistic infection or opportunistic malignancy. Results of this study will yield information regarding the relative therapeutic benefits and toxicities of each drug while providing alternative treatment to patients who are unable to tolerate or have had progression of disease while on AZT. After baseline screening, patients are randomized to one of two treatment arms (ddI or ddC). Subjects are evaluated biweekly for the first 4 weeks of study, at 2 months, and every other month thereafter. Three dose levels of ddI (based on patient's weight at study entry) are compared with two dose levels of ddC (also based on patient weight). Patients who reach a new progression-of-disease primary endpoint after at least 12 weeks of treatment or a drug intolerance endpoint have the option of switching over to the alternate study drug; however, participants are encouraged to remain on their original drug assignment whenever possible. For any switchover, patients must be off the originally assigned drug for at least 72 hours before switching. Only one switchover is allowed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Zalcitabine, Didanosine, Drug Evaluation, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Enrollment
400 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zalcitabine
Intervention Type
Drug
Intervention Name(s)
Didanosine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Acyclovir (if patient is also receiving ddC, clinical monitoring should be more frequent). Analgesics, antiemetics, antidiarrheal agents, or other necessary treatment for symptomatic therapy. Interferons for maintenance therapy of Kaposi's sarcoma. GM-CSF. Required: Prophylaxis against Pneumocystis carinii pneumonia (PCP) if their absolute CD4+ lymphocyte count is < 200 cells/mm3 at study entry. PCP prophylaxis for patient with CD4+ counts between 200 and 300 cells/mm3 is at discretion of patient's primary physician. NOTE: There is potential interaction of ddI and dapsone. Concurrent Treatment: Allowed: Transfusion, erythropoietin. Patients must have the following: Zidovudine (AZT) failure after having received a cumulative duration of at least 6 months. AZT intolerance - rechallenge is not required for patients exhibiting = or > grade III cutaneous symptoms. Diagnosis of AIDS or CD4+ = or < 300 cells/mm3 OR AIDS-defining illness other than Kaposi's sarcoma. Willingness and ability to comply with protocol. Informed consent must be obtained for all study participants in accordance with state law, local IRB requirements, and 45 CFR Part 46. AMENDED 11/19/90 to include assent by minors if they are physically able, in addition to consent by parents. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Any disorders for which the study drugs are contraindicated (didanosine (ddI)) is contraindicated in renal impairment, heart disease, receiving renal dialysis. Active opportunistic infection. Concurrent Medication: Excluded: Other antiretroviral agents. Use of drugs associated with peripheral neuropathy or use of agents that may cause pancreatitis including intravenous pentamidine and alcohol should be restricted or avoided. Concurrent Treatment: Excluded: Other concurrent antiretroviral clinical trials. Patients with the following are excluded: History of pancreatitis, peripheral neuropathy, uncontrolled seizures, renal impairment, heart disease, stage 2 or higher ADC. Any other disorders for which the study drugs are contraindicated, i.e., ddI is contraindicated in renal impairment, patients receiving renal dialysis, and heart disease. Receiving acute therapy for active AIDS defining opportunistic infection on enrollment. Prior Medication: Excluded: Didanosine (ddI). Dideoxycytidine (ddC) . Excessive alcohol use that, in investigator's opinion, puts patient at risk of developing pancreatic disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kaplan C
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Crane L
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Abrams D
Official's Role
Study Chair
Facility Information:
Facility Name
Community Consortium of San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Denver CPCRA / Denver Public Hlth
City
Denver
State/Province
Colorado
ZIP/Postal Code
802044507
Country
United States
Facility Name
Hill Health Corp
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
Wilmington Hosp / Med Ctr of Delaware
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19899
Country
United States
Facility Name
Veterans Administration Med Ctr / Regional AIDS Program
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20422
Country
United States
Facility Name
AIDS Research Consortium of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
AIDS Research Alliance - Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60657
Country
United States
Facility Name
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Comprehensive AIDS Alliance of Detroit
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Hosp
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
North Jersey Community Research Initiative
City
Newark
State/Province
New Jersey
ZIP/Postal Code
071032842
Country
United States
Facility Name
Bronx Lebanon Hosp Ctr
City
Bronx
State/Province
New York
ZIP/Postal Code
10456
Country
United States
Facility Name
Clinical Directors Network of Region II
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
Harlem AIDS Treatment Group / Harlem Hosp Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10037
Country
United States
Facility Name
Portland Veterans Adm Med Ctr / Rsch & Education Grp
City
Portland
State/Province
Oregon
ZIP/Postal Code
972109951
Country
United States
Facility Name
Richmond AIDS Consortium
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9179982
Citation
Bjorling LE, Hodges JS. Rule-based ranking schemes for antiretroviral trials. Stat Med. 1997 May 30;16(10):1175-91. doi: 10.1002/(sici)1097-0258(19970530)16:103.0.co;2-g.
Results Reference
background
Citation
Hogan CH, Hodges JS, Mugglin A, Peterson PM, Abrams DI, Saravolatz L. The perils of visit-driven endpoints in antiretroviral trials. Int Conf AIDS. 1996 Jul 7-12;11(1):237 (abstract no TuB522)
Results Reference
background
PubMed Identifier
7552519
Citation
Fleming TR, Neaton JD, Goldman A, DeMets DL, Launer C, Korvick J, Abrams D. Insights from monitoring the CPCRA didanosine/zalcitabine trial. Terry Beirn Community Programs for Clinical Research on AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10 Suppl 2:S9-18.
Results Reference
background
PubMed Identifier
8556398
Citation
Goldman AI, Carlin BP, Crane LR, Launer C, Korvick JA, Deyton L, Abrams DI. Response of CD4 lymphocytes and clinical consequences of treatment using ddI or ddC in patients with advanced HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Feb 1;11(2):161-9. doi: 10.1097/00042560-199602010-00007.
Results Reference
background
Citation
Abrams D, Goldman A, Launer C, Korvick J, Crane L, Deyton L. Results of a randomized open-label comparison trial of ddI and ddC in HIV infected patients who are intolerant of or have failed ZDV therapy; CPCRA 002. The Terry Beirn Community Programs for Clinical Research on AIDS. Int Conf AIDS. 1993 Jun 6-11;9(1):67 (abstract no WS-B24-4)
Results Reference
background
PubMed Identifier
7906384
Citation
Abrams DI, Goldman AI, Launer C, Korvick JA, Neaton JD, Crane LR, Grodesky M, Wakefield S, Muth K, Kornegay S, et al. A comparative trial of didanosine or zalcitabine after treatment with zidovudine in patients with human immunodeficiency virus infection. The Terry Beirn Community Programs for Clinical Research on AIDS. N Engl J Med. 1994 Mar 10;330(10):657-62. doi: 10.1056/NEJM199403103301001.
Results Reference
background
PubMed Identifier
22222175
Citation
Soeiro-de-Souza MG, Bio DS, David DP, Rodrigues dos Santos D Jr, Kerr DS, Gattaz WF, Machado-Vieira R, Moreno RA. COMT Met (158) modulates facial emotion recognition in bipolar I disorder mood episodes. J Affect Disord. 2012 Feb;136(3):370-6. doi: 10.1016/j.jad.2011.11.021. Epub 2012 Jan 4.
Results Reference
derived

Learn more about this trial

A Prospective, Randomized, Open-Label, Comparative Trial of Dideoxyinosine (ddI) Versus Dideoxycytidine (ddC) in HIV-Infected Patients Who Are Intolerant of or Who Have Failed Zidovudine (AZT) Therapy

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