Nevirapine Study for the Prevention of Maternal-Infant HIV Transmission in Uganda

Tracking Information
First Submitted Date ICMJE	March 18, 2008
First Posted Date ICMJE	March 20, 2008
Last Update Posted Date	April 2, 2008
Study Start Date ICMJE	July 2004
Actual Primary Completion Date	July 2007 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 18, 2008)	Rate of HIV infection in infants born to study participants in each arm of the study [ Time Frame: At Birth, Weeks 2, 6, and 14, and Months 6, 12, and 18 ]; Safety and tolerance of HIVIGLOB given to pregnant women at 36-37 weeks gestation and neonates at birth in combination with NVP and of NVP alone [ Time Frame: Throughout study ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00639938 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 18, 2008)	Rate of immunologic progression in HIV-infected infants in each arm [ Time Frame: Throughout study ]; Infant mortality [ Time Frame: Throughout study ]; Maternal plasma HIV RNA levels at delivery [ Time Frame: At Birth ]; Immunologic, virologic, and pharmacologic factors [ Time Frame: Throughout study ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Nevirapine Study for the Prevention of Maternal-Infant HIV Transmission in Uganda
Official Title ICMJE	A Phase III Randomized Clinical Trial of the Standard Two Dose Nevirapine (NVP) Regimen With the Addition of HIV Immune Globulin(HIVIGLOB) or Extended Infant NVP Dosing Compared With the Standard NVP Regimen Alone for the Prevention of Maternal-Infant HIV Transmission in Uganda
Brief Summary	The increase in pediatric HIV infection has a substantial impact on childhood mortality in the developing world. A number of recent studies suggest that as many as half or more of mother-to-child HIV transmissions in developing countries occur in late pregnancy or during labor and delivery. Interventions targeted during the perinatal period have shown to be effective and to have a significant impact in reducing transmission. The purpose of this study is to investigate the effectiveness of nevirapine (NVP) plus immunoprophylaxis or extended NVP dosing regimens in HIV-infected pregnant women and their infants during the perinatal period.
Detailed Description	There is an urgent need to find safe, effective means of preventing mother-to-child-transmission (MTCT) of HIV that can be used in developing countries. One of the greatest obstacles to prevention in these areas remains HIV transmission through breast milk. The primary purpose of this trial is to determine if nevirapine (NVP) plus immunoprophylaxis (by intravenous HIV immune globulin [HIVIGLOB]) or extended NVP dosing of the neonate during the perinatal period can safely and effectively reduce the risk of peripartum or early breastfeeding-related HIV MTCT. This study will last 11-18 weeks for each mother and 18 months for each infant. HIV-infected pregnant women will be randomly assigned to one of three arms. Participants in Arm 1 will receive a single dose of 200 mg NVP orally at the onset of labor. Infants in Arm 1 will receive a single dose of 2 mg/kg NVP orally within the first week after delivery. Arm 2 participants will receive a single dose of 200 mg NVP orally at the onset of labor. Infants in Arm 2 will receive 2 mg/kg NVP orally within the first week after delivery and 5 mg NVP taken orally daily from Day 8 through Week 6. Arm 3 participants will receive a 12 gm intravenous dose of HIVIGLOB at 36-37 weeks gestation and 200 mg NVP orally at the onset of labor. Infants in Arm 3 will receive a single 1.2 gm intravenous dose HIVIGLOB within 18 hours of birth and 2 mg/kg NVP orally within the first week after delivery. There will be five or six study visits for pregnant participants. A targeted medical history, physical examination, and blood collection will occur at all visits. After birth, there will be 11 study visits for infants in Arms 1 and 2 and 12 study visits for infants in Arm 3. Medical history and a targeted physical exam will occur at all visits. Blood collection will occur at some visits.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Prevention
Condition ICMJE	HIV Infections
Intervention ICMJE	Drug: Nevirapine 200 mg Nevirapine tablet Other Name: NVP Viramune; Drug: HIV immune globulin solution 5% intravenous HIV immune globulin solution Other Name: HIVIGLOB
Study Arms	Active Comparator: 1 Mother dosing regimen: Single dose of 200 mg NVP taken orally at onset of labor Infant dosing regimen: Single dose of 2 mg/kg NVP taken orally within the first week after delivery Intervention: Drug: Nevirapine; Experimental: 2 Mother dosing regimen: Single dose of 200 mg NVP taken orally at onset of labor Infant dosing regimen: 2 mg/kg NVP taken orally within the first week after delivery and 5 mg NVP taken orally daily from Day 8 through Week 6 Intervention: Drug: Nevirapine; Experimental: 3 Mother dosing regimen: Single 12 gm intravenous dose of HIVIGLOB at 36 - 37 weeks gestation and 200 mg NVP taken orally at onset of labor Infant dosing regimen: Single 1.2 gm intravenous dose HIVIGLOB within 18 hours of birth and 2 mg/kg NVP taken orally within the first week after delivery Interventions: Drug: Nevirapine Drug: HIV immune globulin solution
Publications *	Colvin M, Chopra M, Doherty T, Jackson D, Levin J, Willumsen J, Goga A, Moodley P; Good Start Study Group. Operational effectiveness of single-dose nevirapine in preventing mother-to-child transmission of HIV. Bull World Health Organ. 2007 Jun;85(6):466-73.; Flys TS, Mwatha A, Guay LA, Nakabiito C, Donnell D, Musoke P, Mmiro F, Jackson JB, Eshleman SH. Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. AIDS. 2007 Oct 1;21(15):2077-82.; 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.; Onyango-Makumbi C, Omer SB, Mubiru M, Moulton LH, Nakabiito C, Musoke P, Mmiro F, Zwerski S, Wigzell H, Falksveden L, Wahren B, Antelman G, Fowler MG, Guay L, Jackson JB. Safety and efficacy of HIV hyperimmune globulin for prevention of mother-to-child HIV transmission in HIV-1-infected pregnant women and their infants in Kampala, Uganda (HIVIGLOB/NVP STUDY). J Acquir Immune Defic Syndr. 2011 Dec 1;58(4):399-407. doi: 10.1097/QAI.0b013e31822f8914.; Six Week Extended-Dose Nevirapine (SWEN) Study Team, Bedri A, Gudetta B, Isehak A, Kumbi S, Lulseged S, Mengistu Y, Bhore AV, Bhosale R, Varadhrajan V, Gupte N, Sastry J, Suryavanshi N, Tripathy S, Mmiro F, Mubiru M, Onyango C, Taylor A, Musoke P, Nakabiito C, Abashawl A, Adamu R, Antelman G, Bollinger RC, Bright P, Chaudhary MA, Coberly J, Guay L, Fowler MG, Gupta A, Hassen E, Jackson JB, Moulton LH, Nayak U, Omer SB, Propper L, Ram M, Rexroad V, Ruff AJ, Shankar A, Zwerski S. Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet. 2008 Jul 26;372(9635):300-13. doi: 10.1016/S0140-6736(08)61114-9.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 18, 2008)	722
Original Actual Enrollment ICMJE	Same as current
Actual Study Completion Date	July 2007
Actual Primary Completion Date	July 2007 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Pregnant between 32-36 weeks estimated gestation; HIV Infected; Intent to breastfeed infant; Certain laboratory criteria. More information on this criterion can be found in the protocol. Exclusion Criteria: Sensitivity to immune globulin preparations or any benzodiazepine; Clinically significant disease, as determined by the investigator, that would compromise the ability of the participant to complete the study requirements; Currently receiving antiretroviral therapy (other than the intrapartum NVP or other peripartum regimens); Participation in any HIV vaccine trials; History of cytotoxic chemotherapy within one month of study entry; Uncontrolled hypertension; Chronic alcohol or illicit drug use; History of non-compliance with visits or medication; Women who become pregnant again during study follow-up will not be eligible for re-enrollment in the trial
Sex/Gender	Sexes Eligible for Study: Female
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Not Provided
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00639938
Other Study ID Numbers ICMJE	R01AI034235( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Brooks Jackson, MD, Johns Hopkins School of Medicine
Study Sponsor ICMJE	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Brooks Jackson, MD Johns Hopkins School of Medicine
PRS Account	National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date	March 2008
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP