A Phase III Placebo-Controlled Trial to Determine the Efficacy of Oral AZT and the Efficacy of Oral Nevirapine for the Prevention of Vertical Transmission of HIV-1 Infection in Pregnant Ugandan Women and Their Neonates
Effectiveness of AZT and Nevirapine in Preventing HIV Transmission From Ugandan Mothers to Their Newborns
Sponsors
Source
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary
The purpose of this study is to see if nevirapine (NVP) or zidovudine (AZT), given to mothers
during labor and delivery and to their babies during the first week of life, can reduce the
rate of mothers passing HIV to their babies.
About 25 percent of HIV-infected mothers pass HIV infection to their babies during labor and
delivery. There is an urgent need to find a simpler way to prevent mother-to-infant
transmission during labor and delivery. The proposed NVP schedule is simpler and possibly
could be used in Uganda.
Detailed Description
There is an urgent need to find a safe, effective means of preventing mother-to-infant HIV
transmission that would also be applicable and affordable in developing-country settings. The
frequency of vertical HIV-1 transmission is estimated to be 25 percent. The proposed trial
specifically will test the hypothesis that chemoprophylaxis of the fetus/neonate during labor
and delivery and the first week of life may significantly reduce the risk of perinatal HIV-1
transmission.
Pregnant women infected with HIV-1 are randomized to 1 of 4 study arms and receive either NVP
or its placebo, or AZT or its placebo. Mothers in the NVP group receive a single dose of NVP
or placebo at the onset of labor and are followed to 6 to 8 weeks after delivery. Infants
born to these mothers receive at 48 to 72 hours post-delivery or discharge, whichever comes
first, a regimen of the same treatment (NVP or placebo) given to the mother. Infants are
followed for 18 months post-delivery by clinical and laboratory evaluation to determine
toxicity, evidence of HIV-1 infection, and clinical disease progression.
Mothers in the AZT group receive either a bolus of AZT or its placebo at onset of labor, then
doses every 3 hours until delivery, with follow-up to 6 to 8 weeks. Infants begin receiving
either a lower dose of AZT or placebo as soon as they can tolerate liquids by mouth, twice
daily for 7 days, and are followed for 18 months as in the NVP group.
Overall Status
Completed
Start Date
N/A
Completion Date
2004-11-01
Primary Completion Date
N/A
Phase
Phase 3
Study Type
Interventional
Enrollment
1500
Condition
Intervention
Eligibility
Criteria
Inclusion Criteria
Mothers may be eligible for this study if they:
- Have been pregnant for more than 32 weeks and are at least 18 years of age.
- Are HIV-positive.
- Reside within 15 km of Mulago Hospital, the study site.
- Infants may be eligible for this study if they:
- Are born to mothers enrolled in the study.
- Have consent of the mother/guardian and, if available, the father.
Exclusion Criteria
Mothers will not be eligible for this study if they:
- Have a serious infection or illness other than HIV.
- Currently take any anti-HIV drugs.
- Participate during this pregnancy in another treatment vaccine perinatal trial.
- Received NVP or AZT within the last 6 months.
- Are allergic to any benzodiazepine.
- Abuse alcohol or other drugs.
- Have high blood pressure that is not controlled.
- Have received any anticoagulants, benzodiazepines other than the study drug, or
magnesium sulfate within 2 weeks before being assigned to a study group or delivery.
- Infants will not be eligible for this study if:
- Their mother is excluded prior to being assigned to a study group.
Gender
All
Minimum Age
N/A
Maximum Age
N/A
Healthy Volunteers
Accepts Healthy Volunteers
Overall Official
Last Name |
Role |
|
Brooks Jackson |
Study Chair |
|
Francis Mmiro |
Study Chair |
|
Laura Guay |
Study Chair |
|
Philippa Musoke |
Study Chair |
Location
Facility |
|
Missie Allen Research Triangle Park North Carolina 27709 United States |
Location Countries
Country
United States
Verification Date
2012-02-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
11719
Intervention Browse
Mesh Term
Zidovudine
Nevirapine
Results Reference
Citation
Guay LA, Musoke P, Fleming T, Bagenda D, Allen M, Nakabiito C, Sherman J, Bakaki P, Ducar C, Deseyve M, Emel L, Mirochnick M, Fowler MG, Mofenson L, Miotti P, Dransfield K, Bray D, Mmiro F, Jackson JB. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet. 1999 Sep 4;354(9181):795-802.
PMID
10485720
Citation
Jackson JB, Musoke P, Fleming T, Guay LA, Bagenda D, Allen M, Nakabiito C, Sherman J, Bakaki P, Owor M, Ducar C, Deseyve M, Mwatha A, Emel L, Duefield C, Mirochnick M, Fowler MG, Mofenson L, Miotti P, Gigliotti M, Bray D, Mmiro F. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet. 2003 Sep 13;362(9387):859-68.
PMID
13678973
Citation
Eshleman SH, Guay LA, Mwatha A, Brown ER, Cunningham SP, Musoke P, Mmiro F, Jackson JB. Characterization of nevirapine resistance mutations in women with subtype A vs. D HIV-1 6-8 weeks after single-dose nevirapine (HIVNET 012). J Acquir Immune Defic Syndr. 2004 Feb 1;35(2):126-30.
PMID
14722443
Citation
Eshleman SH, Guay LA, Fleming T, Mwatha A, Mracna M, Becker-Pergola G, Musoke P, Mmiro F, Jackson JB. Survival of Ugandan infants with subtype A and D HIV-1 infection (HIVNET 012). J Acquir Immune Defic Syndr. 2002 Nov 1;31(3):327-30.
PMID
12439209
Citation
Eshleman SH, Becker-Pergola G, Deseyve M, Guay LA, Mracna M, Fleming T, Cunningham S, Musoke P, Mmiro F, Jackson JB. Impact of human immunodeficiency virus type 1 (hiv-1) subtype on women receiving single-dose nevirapine prophylaxis to prevent hiv-1 vertical transmission (hiv network for prevention trials 012 study). J Infect Dis. 2001 Oct 1;184(7):914-7. Epub 2001 Aug 13.
PMID
11509999
Citation
Eshleman SH, Guay LA, Mwatha A, Cunningham SP, Brown ER, Musoke P, Mmiro F, Jackson JB. Comparison of nevirapine (NVP) resistance in Ugandan women 7 days vs. 6-8 weeks after single-dose nvp prophylaxis: HIVNET 012. AIDS Res Hum Retroviruses. 2004 Jun;20(6):595-9.
PMID
15242535
Citation
Eshleman SH, Guay LA, Wang J, Mwatha A, Brown ER, Musoke P, Mmiro F, Jackson JB. Distinct patterns of emergence and fading of K103N and Y181C in women with subtype A vs. D after single-dose nevirapine: HIVNET 012. J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):24-9.
PMID
16123677
Citation
Jackson JB, Parsons T, Musoke P, Nakabiito C, Donnell D, Fleming T, Mirochnick M, Mofenson L, Fowler MG, Mmiro F, Guay L. Association of cord blood nevirapine concentration with reported timing of dose and HIV-1 transmission. AIDS. 2006 Jan 9;20(2):217-22.
PMID
16511414
Citation
Eshleman SH, Hoover DR, Chen S, Hudelson SE, Guay LA, Mwatha A, Fiscus SA, Mmiro F, Musoke P, Jackson JB, Kumwenda N, Taha T. Resistance after single-dose nevirapine prophylaxis emerges in a high proportion of Malawian newborns. AIDS. 2005 Dec 2;19(18):2167-9.
PMID
16284468
Firstreceived Results Date
N/A
Reference
Citation
Eshleman SH, Mracna M, Guay LA, Deseyve M, Cunningham S, Mirochnick M, Musoke P, Fleming T, Glenn Fowler M, Mofenson LM, Mmiro F, Jackson JB. Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012). AIDS. 2001 Oct 19;15(15):1951-7.
PMID
11600822
Firstreceived Results Disposition Date
N/A
Study Design Info
Primary Purpose
Prevention
Masking
Double
Study First Submitted
October 10, 2000
Study First Submitted Qc
August 30, 2001
Study First Posted
August 31, 2001
Last Update Submitted
February 13, 2012
Last Update Submitted Qc
February 13, 2012
Last Update Posted
February 14, 2012
ClinicalTrials.gov processed this data on December 13, 2019
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Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.