HIV InfectionsNCT00000719
A Trial of Alternating 2',3'-Dideoxycytidine and Zidovudine in the Treatment of Patients With Advanced HIV Disease
A study testing Zidovudine and Zalcitabine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
Trial summary
To determine the long-term safety and tolerance of four alternating and two intermittent regimens of zidovudine ( AZT ) and 2',3'-dideoxycytidine ( zalcitabine; ddC ) in the treatment of patients with advanced HIV disease who have had to discontinue AZT because of true hematologic intolerance to standard reduced doses… Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Zidovudine and Zalcitabine
- How many people
- 96 participants
- Where
- 7 sitesUnited States
- Study dates
- Start not givento Feb 1995
- Phase
- Interventional
- 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 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Concurrent Medication:
- Allowed:
- Aerosolized pentamidine at prophylactic doses, but its use is discouraged in persons without a history of Pneumocystis carinii pneumonia (PCP).
- Acyclovir for acute disseminated zoster.
- Maintenance doses of pyrimethamine, amphotericin, and pentamidine are allowed for patients who recover from toxoplasmosis, cryptococcosis, or pneumocystosis acquired after study entry.
- Patients included in the study must have HIV infection confirmed by ELISA test and must have a documented history of at least 4 weeks of zidovudine (AZT) treatment.
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- While hemoglobin at the start of AZT therapy must have been = or > 9.5 g/dl and granulocyte count = or > 1200 cells/mm3 at the start of AZT therapy, hematologic toxicity due to a reduced dose of AZT will be defined as:
- Hematologic toxicity must have occurred during a period when AZT was administered at = or < 600 mg/day for at least 2 weeks.
- There must have been no evidence of a cause for toxicity other than HIV infection and AZT use.
- Hematologic intolerance may have consisted of hemoglobin toxicity, granulocyte toxicity, or both.
- Recovery from hematologic toxicity must be manifested by the presence of a granulocyte count of > 1000 cells/mm3 and a hemoglobin of > 9.5 g/dl. without transfusions during the preceding 4 weeks. Patients must also have no significant bilateral symptoms of peripheral neuropathy, although all patients may have any degree of stable unilateral neurologic deficit. Up to 24 patients may have certain moderate bilateral abnormalities of peripheral neuropathy. AZT may not have been administered within 14 days prior to entering the study.
- Prior Medication:
- Required:
- A documented history of at least 4 weeks of zidovudine treatment which resulted in hematologic toxicity at reduced dose.
- Allowed but discouraged:
- A1-721.
Who cannot join
- Co-existing Condition:
- Patients with the following are excluded:
- Known active AIDS opportunistic infections.
- Known mycobacteremia, although cultures may be pending at the time of enrollment.
- Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study or with concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix.
- Significant malabsorption as manifested by steatorrhea with greater than 10 percent weight loss within the last 3 months.
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- Diabetes.
- Concurrent Medication:
- Excluded:
- Experimental medications.
- Aspirin.
- Acetaminophen.
- Nonsteroidal anti-inflammatory agents should be minimized, with continuous use for > 72 hours discouraged.
- Chronic suppressive anti-infective therapy other than inhaled pentamidine and neurotoxic drugs should be avoided.
- Continuous therapy for > 7 days of acyclovir is prohibited except for the acute treatment of disseminated herpes zoster infection.
- Patients with the following are excluded:
- Known mycobacteremia, although cultures may be pending at the time of enrollment.
- Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study or with concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix.
- Significant malabsorption as manifested by steatorrhea with greater than 10 percent weight loss within the last 3 months.
- Diabetes.
- Known active AIDS opportunistic infections. Patients must also have no significant bilateral symptoms of peripheral neuropathy, although all patients may have any degree of stable unilateral neurologic deficit. Up to 24 patients may have certain moderate bilateral abnormalities of peripheral neuropathy. AZT may not have been administered within 14 days prior to entering the study.
- Prior Medication:
- Excluded within 30 days of study entry:
- Any antiretroviral agents except zidovudine (AZT).
- Discouraged:
- A1-721.
- Pentamidine at prophylactic doses in persons without a history of Pneumocystis carinii pneumonia (PCP).
- Active substance and/or alcohol abuse.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Northwestern University CRS
Chicago, Illinois, 60611
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois
USC CRS
Los Angeles, California, 90033
Univ. of Miami AIDS CRS
Miami, Florida, 33136
University of Minnesota, ACTU
Minneapolis, Minnesota, 55455
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, 70112
Ucsd, Avrc Crs
San Diego, California, 92103
About this study
To determine the long-term safety and tolerance of four alternating and two intermittent regimens of zidovudine ( AZT ) and 2',3'-dideoxycytidine ( zalcitabine; ddC ) in the treatment of patients with advanced HIV disease who have had to discontinue AZT because of true hematologic intolerance to standard reduced doses of AZT.
AIDS is a serious infectious disease caused by a new family of retrovirus which is spread primarily through sexual contact and administration of blood or blood products. Individuals who are infected with HIV could therefore benefit from therapy with an effective anti-AIDS virus agent. AZT and ddC have both been tested as antiviral agents and their potentially beneficial effects may be limited by time- and dose-dependent toxicity. A combination regimen using shorter courses of AZT and ddC might therefore be able to sustain treatment without producing toxicity. In addition, since the two drugs exhibit their major toxicity on different organ systems, cumulative or additive toxicity would not be expected.
Read the detailed description
AIDS is a serious infectious disease caused by a new family of retrovirus which is spread primarily through sexual contact and administration of blood or blood products. Individuals who are infected with HIV could therefore benefit from therapy with an effective anti-AIDS virus agent. AZT and ddC have both been tested as antiviral agents and their potentially beneficial effects may be limited by time- and dose-dependent toxicity. A combination regimen using shorter courses of AZT and ddC might therefore be able to sustain treatment without producing toxicity. In addition, since the two drugs exhibit their major toxicity on different organ systems, cumulative or additive toxicity would not be expected.
There are six study regimens. Four of these are alternating regimens: A 2-week cycle consisting of 1 week of AZT followed by 1 week of ddC and an 8-week cycle consisting of 4 weeks of AZT followed by 4 weeks of ddC. All patients on alternating regimens will receive AZT alone at the standard dose orally every 4 hours for either 1 or 4 weeks. After the AZT is stopped, patients receive ddC orally every 4 hours for either 1 or 4 weeks, which completes a treatment cycle. One of two doses of ddC is studied in each alternating regimen. Both doses must be tested because the optimal dose cannot be inferred from tests that have already been done. AZT is administered first in the hope that AZT-mediated reduction of p24 antigen load may reduce the occurrence of acute ddC toxicity. Two intermittent regimens are also studied and are included to assess the contribution of each drug in the alternating regimens. One program consists of 1 week of AZT followed by 1 week of no drug. The other consists of 1 week of ddC followed by 1 week of no drug. Drug dosing continues for a total of 48 weeks unless toxicity develops. Patients who complete 48 weeks of therapy are followed for 4 additional weeks off therapy. Patients removed from study because of toxicity are followed for 4 weeks or until toxicity resolves. If study participants complete 48 weeks of therapy and meet criteria for efficacy, the study drug regimen may be continued for an additional 32 weeks. A 4 week wash-out period off drug will not be required for patients continuing on study. AMENDED 09/24/90 Drug dosing will be discontinued as of 11/30/90.
- Conditions
- HIV Infections
- Being tested
- Zidovudine, Zalcitabine
- Keywords
- Zalcitabine, Acquired Immunodeficiency Syndrome, Zidovudine
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZidovudineDrug
ZalcitabineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionFeb 1995
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 96 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- S Bozzette, Study chairD Richman, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000719
- Sponsor's protocol ID
- ACTG 050
- Other IDs
- 11024
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 3 Nov 2021
- Results posted
- No
Publications
Lathey JL, Marschner IC, Kabat B, Spector SA. Deterioration of detectable human immunodeficiency virus serum p24 antigen in samples stored for batch testing. J Clin Microbiol. 1997 Mar;35(3):631-5. doi: 10.1128/jcm.35.3.631-635.1997.
PubMed 9041402Gries JM, Troconiz IF, Verotta D, Jacobson M, Sheiner LB. A pooled analysis of CD4 response to zidovudine and zalcitabine treatment in patients with AIDS and AIDS-related complex. Clin Pharmacol Ther. 1997 Jan;61(1):70-82. doi: 10.1016/S0009-9236(97)90183-1.
PubMed 9024175Fichtenbaum 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 7552481Bozzette SA, Richman DD. Salvage therapy for zidovudine-intolerant HIV-infected patients with alternating and intermittent regimens of zidovudine and dideoxycytidine. Am J Med. 1990 May 21;88(5B):24S-26S. doi: 10.1016/0002-9343(90)90418-d.
PubMed 2159706LeLacheur SF, Simon GL. Exacerbation of dideoxycytidine-induced neuropathy with dideoxyinosine. J Acquir Immune Defic Syndr (1988). 1991;4(5):538-9.
PubMed 1849990Bozzette S, Skowron G, Arrezo J, Spector SA, Pettinelli C, Richman DD. ACTG 050: alternating (alt) and intermittent (INT) ddc and AZT in the treatment of persons with advanced HIV infection and hematologic intolerance to AZT. Int Conf AIDS. 1990 Jun 20-23;6(3):192 (abstract no SB425)
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of Alternating 2',3'-Dideoxycytidine and Zidovudine in the Treatment of Patients With Advanced HIV Disease
- ClinicalTrials.gov ID
- NCT00000719
- Acronym / sponsor ID
- ACTG 050
- Conditions
- HIV Infections
- Keywords
- Zalcitabine, Acquired Immunodeficiency Syndrome, Zidovudine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Feb 1995 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the long-term safety and tolerance of four alternating and two intermittent regimens of zidovudine ( AZT ) and 2',3'-dideoxycytidine ( zalcitabine; ddC ) in the treatment of patients with advanced HIV disease who have had to discontinue AZT because of true hematologic intolerance to standard reduced doses of AZT.
AIDS is a serious infectious disease caused by a new family of retrovirus which is spread primarily through sexual contact and administration of blood or blood products. Individuals who are infected with HIV could therefore benefit from therapy with an effective anti-AIDS virus agent. AZT and ddC have both been tested as antiviral agents and their potentially beneficial effects may be limited by time- and dose-dependent toxicity. A combination regimen using shorter courses of AZT and ddC might therefore be able to sustain treatment without producing toxicity. In addition, since the two drugs exhibit their major toxicity on different organ systems, cumulative or additive toxicity would not be expected.
Detailed description
AIDS is a serious infectious disease caused by a new family of retrovirus which is spread primarily through sexual contact and administration of blood or blood products. Individuals who are infected with HIV could therefore benefit from therapy with an effective anti-AIDS virus agent. AZT and ddC have both been tested as antiviral agents and their potentially beneficial effects may be limited by time- and dose-dependent toxicity. A combination regimen using shorter courses of AZT and ddC might therefore be able to sustain treatment without producing toxicity. In addition, since the two drugs exhibit their major toxicity on different organ systems, cumulative or additive toxicity would not be expected.
There are six study regimens. Four of these are alternating regimens: A 2-week cycle consisting of 1 week of AZT followed by 1 week of ddC and an 8-week cycle consisting of 4 weeks of AZT followed by 4 weeks of ddC. All patients on alternating regimens will receive AZT alone at the standard dose orally every 4 hours for either 1 or 4 weeks. After the AZT is stopped, patients receive ddC orally every 4 hours for either 1 or 4 weeks, which completes a treatment cycle. One of two doses of ddC is studied in each alternating regimen. Both doses must be tested because the optimal dose cannot be inferred from tests that have already been done. AZT is administered first in the hope that AZT-mediated reduction of p24 antigen load may reduce the occurrence of acute ddC toxicity. Two intermittent regimens are also studied and are included to assess the contribution of each drug in the alternating regimens. One program consists of 1 week of AZT followed by 1 week of no drug. The other consists of 1 week of ddC followed by 1 week of no drug. Drug dosing continues for a total of 48 weeks unless toxicity develops. Patients who complete 48 weeks of therapy are followed for 4 additional weeks off therapy. Patients removed from study because of toxicity are followed for 4 weeks or until toxicity resolves. If study participants complete 48 weeks of therapy and meet criteria for efficacy, the study drug regimen may be continued for an additional 32 weeks. A 4 week wash-out period off drug will not be required for patients continuing on study. AMENDED 09/24/90 Drug dosing will be discontinued as of 11/30/90.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- Aerosolized pentamidine at prophylactic doses, but its use is discouraged in persons without a history of Pneumocystis carinii pneumonia (PCP).
- Acyclovir for acute disseminated zoster.
- Maintenance doses of pyrimethamine, amphotericin, and pentamidine are allowed for patients who recover from toxoplasmosis, cryptococcosis, or pneumocystosis acquired after study entry.
- Patients included in the study must have HIV infection confirmed by ELISA test and must have a documented history of at least 4 weeks of zidovudine (AZT) treatment.
- While hemoglobin at the start of AZT therapy must have been = or > 9.5 g/dl and granulocyte count = or > 1200 cells/mm3 at the start of AZT therapy, hematologic toxicity due to a reduced dose of AZT will be defined as:
Key exclusion criteria (28 listed)
- Known active AIDS opportunistic infections.
- Known mycobacteremia, although cultures may be pending at the time of enrollment.
- Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study or with concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix.
- Significant malabsorption as manifested by steatorrhea with greater than 10 percent weight loss within the last 3 months.
- Diabetes.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zidovudine | Drug | – |
| Zalcitabine | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2021.
- Background: PubMed 9041402Lathey JL, Marschner IC, Kabat B, Spector SA. Deterioration of detectable human immunodeficiency virus serum p24 antigen in samples stored for batch testing. J Clin Microbiol. 1997 Mar;35(3):631-5. doi: 10.1128/jcm.35.3.631-635.1997.
- Background: PubMed 9024175Gries JM, Troconiz IF, Verotta D, Jacobson M, Sheiner LB. A pooled analysis of CD4 response to zidovudine and zalcitabine treatment in patients with AIDS and AIDS-related complex. Clin Pharmacol Ther. 1997 Jan;61(1):70-82. doi: 10.1016/S0009-9236(97)90183-1.
- Background: PubMed 7552481Fichtenbaum 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.
- Background: PubMed 2159706Bozzette SA, Richman DD. Salvage therapy for zidovudine-intolerant HIV-infected patients with alternating and intermittent regimens of zidovudine and dideoxycytidine. Am J Med. 1990 May 21;88(5B):24S-26S. doi: 10.1016/0002-9343(90)90418-d.
- Background: PubMed 1849990LeLacheur SF, Simon GL. Exacerbation of dideoxycytidine-induced neuropathy with dideoxyinosine. J Acquir Immune Defic Syndr (1988). 1991;4(5):538-9.
- BackgroundBozzette S, Skowron G, Arrezo J, Spector SA, Pettinelli C, Richman DD. ACTG 050: alternating (alt) and intermittent (INT) ddc and AZT in the treatment of persons with advanced HIV infection and hematologic intolerance to AZT. Int Conf AIDS. 1990 Jun 20-23;6(3):192 (abstract no SB425)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
S Bozzette study chair
D Richman study chair
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Zidovudine and Zalcitabine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
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 16 inclusion and 28 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 3 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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.
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 NCT00000719, which also lists 6 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 3 Nov 2021.