HIV InfectionsPhase 1NCT00000952
A Study of Ritonavir (an Anti-HIV Drug) in HIV-Positive Infants and Children
A Phase 1 study testing Ritonavir, Lamivudine and Zidovudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in United States.
Trial summary
The study examines the safety and effectiveness of ritonavir (an anti-HIV drug), alone and in combination with other anti-HIV drugs, in HIV-positive children under 2 years of age. This study will also determine the most effective doses of ritonavir for future pediatric HIV studies. Read more about this study
- Who is it for?
- Ages 1 month to 2 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Ritonavir, Lamivudine and Zidovudine
- How many people
- 60 participants
- Where
- 12 sitesUnited States
- Study dates
- Start not givento Jan 2004
- Phase
- Phase 1
- 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 1 month to 2 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children may be eligible for this study if they:
- Are HIV-positive. (Infants under 3 months old presumed to be HIV-positive are eligible to participate in the single-dose phase of the study.)
- Are between the ages of 4 weeks and 2 years (consent of parent or guardian required).
Who cannot join
- Children will not be eligible for this study if they:
- Have an opportunistic (AIDS-related) infection within 2 months of study entry.
- Are allergic to 3TC and/or ZDV.
- Have received anti-HIV drugs for 6 to 12 weeks.
- Have any infections requiring treatment.
- Are experiencing wasting (significant weight loss).
- Have any malignancies (cancer).
- Have certain immune diseases, are being fed through a tube, or have HIV-related encephalopathy (a degenerative disease of the brain).
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
Boston, Massachusetts, 02115
Long Beach Memorial Med. Ctr., Miller Children's Hosp.
Long Beach, California, 90806
St. Jude/UTHSC CRS
Memphis, Tennessee, 38105
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, 70112
NYU Med. Ctr., Dept. of Medicine
New York, New York, 10016
Nyu Ny Nichd Crs
New York, New York, 10016
Columbia IMPAACT CRS
New York, New York, 10032
Incarnation Children's Ctr.
New York, New York, 10032
Harlem Hosp. Ctr. NY NICHD CRS
New York, New York, 10037
The Children's Hosp. of Philadelphia IMPAACT CRS
Philadelphia, Pennsylvania, 19104
UCSD Maternal, Child, and Adolescent HIV CRS
San Diego, California, 92103
Howard Univ. Washington DC NICHD CRS
Washington D.C., District of Columbia, 20060
About this study
Official title: A Phase I/II Study of Ritonavir Therapy in HIV-1 Infected Infants and Children
The study examines the safety and effectiveness of ritonavir (an anti-HIV drug), alone and in combination with other anti-HIV drugs, in HIV-positive children under 2 years of age. This study will also determine the most effective doses of ritonavir for future pediatric HIV studies.
Infants infected with HIV by their mothers experience faster disease progression than adults or older children. Treatment with anti-HIV drugs administered at an early age may slow disease progression in infant populations.
Read the detailed description
As a group, vertically infected children experience more rapid disease progression than children infected at an older age or adults. The early administration of potent antiretroviral regimens might significantly impact the course of vertical HIV-1 infection.
Infants and children are stratified by age, representative of the developmental differences related to drug metabolism (Group I: at least 6 months - 2 years, Group II: 3-6 months, Group IIIA: 1 month - 10 weeks, IIIB: 1 month - less than 3 months). Within each age group there will be two possible dosage cohorts. All age groups will be enrolled simultaneously into dosage Cohort I, at the initial drug dosage. Progression to Cohort II (at a higher or lower drug dosage) will be decided according to safety, tolerance or viral load in Cohort I. All therapy for Group I/II, whether in Cohort I or II, will be introduced as follows: single dose of ritonavir on Day 0, ritonavir monotherapy through Day 7 AM and combination therapy from Day 7 PM through Week 104. All therapy for Group IIIA \& IIIB, whether in Cohort I or II, will be introduced as follows: single dose of ritonavir on Day 0 AM and transition to combination therapy Day 0 PM through Week 104. NOTE: Progression to combination therapy for Group IIIA infants is dependent upon the results of the single-dose ritonavir pharmacokinetics (PK). If the patient is no longer at least presumed to be HIV-infected, he/she will be discontinued from the study. Replacement infants, who will not receive the single dose of ritonavir, will be acquired from Group IIIB infants; new infants that are either presumed HIV infected or have already been shown to be HIV-infected. Clinical evaluations are conducted and blood and urine samples collected regularly during the treatment period in order to quantify HIV-1 levels and determine body chemistries. Pharmacokinetic studies require additional blood sampling up to Week 16. [AS PER AMENDMENT 6/30/98: Pharmacokinetics data from Cohort I showed that the proposed Cohort II starting dose was too low. The dose for Cohort II is now increased. All subjects in Groups I, II, and III will begin combination therapy on Day 0 at the increased dose.] [AS PER AMENDMENT 3/13/00: The study has been extended for an additional 104 weeks, provided the patient's viral load is undetectable (below 400 copies/ml) at the end of the initial study period. While on the treatment extension, patients must continue their current schedule for study drug administration and completion of study visits.]
- Conditions
- HIV Infections
- Being tested
- Ritonavir, Lamivudine, Zidovudine
- Keywords
- Dose-Response Relationship, Drug, Drug Therapy, Combination, Zidovudine, HIV Protease Inhibitors, Ritonavir, Lamivudine, Anti-HIV Agents
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RitonavirDrug
LamivudineDrug
ZidovudineDrug
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 completionJan 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 1
- Primary purpose
- Treatment
- Enrolment
- 60 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Ram Yogev, Study chairEllen Chadwick, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000952
- Sponsor's protocol ID
- ACTG 345
- Other IDs
- 10602, PACTG 345
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 29 Oct 2021
- Results posted
- No
Publications
Scott ZA, Chadwick EG, Catalina MD, McManus M, Yogev R, Palumbo P, Britto P, Sullivan JL, Luzuriaga K. HIV-1-specific CD8+T cells in vertically infected infants: early responses and the effects of antiretroviral therapy. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 169)
Zhao Y, Vetterick T, Lewis D, Yu M, Chadwick E, Yogev R, Coberly SK, Palumbo P. Genotypic mutations in the protease (Pr) and reverse transcriptase (RT) genes associated with antiretroviral resistance to combination therapy with ritonavir/AZT/3TC: a virological sub-study of PACTG 345. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 467)
Chadwick EG, Rodman JH, Britto P, Powell C, Palumbo P, Luzuriaga K, Hughes M, Abrams EJ, Flynn PM, Borkowsky W, Yogev R; PACTG Protocol 345 Team. Ritonavir-based highly active antiretroviral therapy in human immunodeficiency virus type 1-infected infants younger than 24 months of age. Pediatr Infect Dis J. 2005 Sep;24(9):793-800. doi: 10.1097/01.inf.0000177281.93658.df.
PubMed 16148846
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Ritonavir Therapy in HIV-1 Infected Infants and Children
- ClinicalTrials.gov ID
- NCT00000952
- Acronym / sponsor ID
- ACTG 345
- Conditions
- HIV Infections
- Keywords
- Dose-Response Relationship, Drug, Drug Therapy, Combination, Zidovudine, HIV Protease Inhibitors, Ritonavir, Lamivudine, Anti-HIV Agents
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study completion
- Jan 2004 (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.
The study examines the safety and effectiveness of ritonavir (an anti-HIV drug), alone and in combination with other anti-HIV drugs, in HIV-positive children under 2 years of age. This study will also determine the most effective doses of ritonavir for future pediatric HIV studies.
Infants infected with HIV by their mothers experience faster disease progression than adults or older children. Treatment with anti-HIV drugs administered at an early age may slow disease progression in infant populations.
Detailed description
As a group, vertically infected children experience more rapid disease progression than children infected at an older age or adults. The early administration of potent antiretroviral regimens might significantly impact the course of vertical HIV-1 infection.
Infants and children are stratified by age, representative of the developmental differences related to drug metabolism (Group I: at least 6 months - 2 years, Group II: 3-6 months, Group IIIA: 1 month - 10 weeks, IIIB: 1 month - less than 3 months). Within each age group there will be two possible dosage cohorts. All age groups will be enrolled simultaneously into dosage Cohort I, at the initial drug dosage. Progression to Cohort II (at a higher or lower drug dosage) will be decided according to safety, tolerance or viral load in Cohort I. All therapy for Group I/II, whether in Cohort I or II, will be introduced as follows: single dose of ritonavir on Day 0, ritonavir monotherapy through Day 7 AM and combination therapy from Day 7 PM through Week 104. All therapy for Group IIIA \& IIIB, whether in Cohort I or II, will be introduced as follows: single dose of ritonavir on Day 0 AM and transition to combination therapy Day 0 PM through Week 104. NOTE: Progression to combination therapy for Group IIIA infants is dependent upon the results of the single-dose ritonavir pharmacokinetics (PK). If the patient is no longer at least presumed to be HIV-infected, he/she will be discontinued from the study. Replacement infants, who will not receive the single dose of ritonavir, will be acquired from Group IIIB infants; new infants that are either presumed HIV infected or have already been shown to be HIV-infected. Clinical evaluations are conducted and blood and urine samples collected regularly during the treatment period in order to quantify HIV-1 levels and determine body chemistries. Pharmacokinetic studies require additional blood sampling up to Week 16. [AS PER AMENDMENT 6/30/98: Pharmacokinetics data from Cohort I showed that the proposed Cohort II starting dose was too low. The dose for Cohort II is now increased. All subjects in Groups I, II, and III will begin combination therapy on Day 0 at the increased dose.] [AS PER AMENDMENT 3/13/00: The study has been extended for an additional 104 weeks, provided the patient's viral load is undetectable (below 400 copies/ml) at the end of the initial study period. While on the treatment extension, patients must continue their current schedule for study drug administration and completion of study visits.]
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 1 month to 2 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Are HIV-positive. (Infants under 3 months old presumed to be HIV-positive are eligible to participate in the single-dose phase of the study.)
- Are between the ages of 4 weeks and 2 years (consent of parent or guardian required).
Key exclusion criteria (8 listed)
- Have an opportunistic (AIDS-related) infection within 2 months of study entry.
- Are allergic to 3TC and/or ZDV.
- Have received anti-HIV drugs for 6 to 12 weeks.
- Have any infections requiring treatment.
- Are experiencing wasting (significant weight loss).
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 |
|---|---|---|
| Ritonavir | Drug | – |
| Lamivudine | Drug | – |
| Zidovudine | 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 29 Oct 2021.
- BackgroundScott ZA, Chadwick EG, Catalina MD, McManus M, Yogev R, Palumbo P, Britto P, Sullivan JL, Luzuriaga K. HIV-1-specific CD8+T cells in vertically infected infants: early responses and the effects of antiretroviral therapy. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 169)
- BackgroundZhao Y, Vetterick T, Lewis D, Yu M, Chadwick E, Yogev R, Coberly SK, Palumbo P. Genotypic mutations in the protease (Pr) and reverse transcriptase (RT) genes associated with antiretroviral resistance to combination therapy with ritonavir/AZT/3TC: a virological sub-study of PACTG 345. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 467)
- Results publication: PubMed 16148846Chadwick EG, Rodman JH, Britto P, Powell C, Palumbo P, Luzuriaga K, Hughes M, Abrams EJ, Flynn PM, Borkowsky W, Yogev R; PACTG Protocol 345 Team. Ritonavir-based highly active antiretroviral therapy in human immunodeficiency virus type 1-infected infants younger than 24 months of age. Pediatr Infect Dis J. 2005 Sep;24(9):793-800. doi: 10.1097/01.inf.0000177281.93658.df.
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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.
Ram Yogev study chair
Ellen Chadwick study chair
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ritonavir, Lamivudine and Zidovudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 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 3 inclusion and 8 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 29 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 NCT00000952, which also lists 3 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 29 Oct 2021.