Nevirapine Dosing in Neonates for Prophylaxis of Mother-to-Child-Transmission (MTCT) of HIV Infection

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by The Hospital for Sick Children
Sponsor:
Collaborators:
Canadian Foundation for AIDS Research (CANFAR)
Children's Hospital of Eastern Ontario
St. Michael's Hospital, Toronto
Mount Sinai Hospital, Canada
Information provided by (Responsible Party):
Ari Bitnun, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT02166502
First received: June 5, 2014
Last updated: June 14, 2014
Last verified: June 2014

June 5, 2014
June 14, 2014
February 2012
February 2016   (final data collection date for primary outcome measure)
Proportion of nevirapine trough (Cmin) plasma levels that are above or below the target range for prophylaxis [ Time Frame: Weeks 1, 2, and 4 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT02166502 on ClinicalTrials.gov Archive Site
  • Final dose of nevirapine [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Final dose of nevirapine required to achieve target plasma trough concentrations at week 4
  • Derived pharmacokinetic parameters [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Derived pharmacokinetic parameters volume of distribution (Vd)(L/kg), elimination rate (ke), clearance (mL/kg/hr), Cmin (ug/L), Cmax (ug/L), Tmax (hrs), and Area under the Curve (AUC)
  • Association between nevirapine levels and incidence of adverse effects [ Time Frame: Weeks 1, 2 and 4 ] [ Designated as safety issue: Yes ]
    Number of adverse events among patients with therapeutic vs. supratherapeutic nevirapine levels
  • Association between patient characteristics and differences in nevirapine levels [ Time Frame: Baseline, Week 1, 2 and 4 ] [ Designated as safety issue: No ]
    Patient characteristics that may explain differences in nevirapine levels including chronologic and gestational age, weight, and ethnic background.
  • Rate of vertical transmission of HIV [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Nevirapine Dosing in Neonates for Prophylaxis of Mother-to-Child-Transmission (MTCT) of HIV Infection
Nevirapine Dosing in Neonates for Prophylaxis of Mother-to-Child-Transmission (MTCT) of HIV Infection

The purpose of this study is to determine whether the current dose of nevirapine recommended in the Ontario Ministry of Health vertical transmission prevention protocol achieves therapeutic drug levels in newborn infants at high risk of HIV infection.

Although nevirapine (NVP) is often given as part of combination antiretroviral therapy (cART) at our institutions for prevention of vertical transmission (VT) in high risk infants, the optimal prophylactic dose of nevirapine is unknown. The National Institute of Health (NIH) guidelines currently recommend a single 2 mg/kg dose of nevirapine given to the infant within 72 hours of birth, however, this dose is not being used in practice given the controversies previously described with single-dose nevirapine. In the absence of any guidance to inform the multiple daily dosing of nevirapine for prophylaxis of VT, we are currently using the treatment dose for infants >15 days of age of 150 mg/m2 once daily for 14 days, then increasing to 150 mg/m2 twice daily for 14 days. This is analogous to the treatment dosing of triple antiretrovirals (ARVs) that is given for occupational post-exposure prophylaxis. Nevirapine is given for 4 weeks total with zidovudine (AZT) and lamivudine (3TC), followed by 2 additional weeks of AZT and 3TC to prevent the development of nevirapine resistance from its long half life. Stopping all 3 drugs simultaneously would result in a period of functional NVP monotherapy, resulting in a risk of NVP resistance should the infant become infected despite prophylaxis. Since the dose of nevirapine being used in our clinic populations for prevention of VT is higher than has been previously studied in neonates, it is important to evaluate the safety and efficacy of this dosing regimen, using therapeutic drug monitoring.

Observational
Observational Model: Case-Only
Time Perspective: Prospective
Not Provided
Not Provided
Non-Probability Sample

The patients in this study are newborn infants clinically prescribed combination antiretroviral treatment with nevirapine for prevention of mother-to-child HIV transmission. These infants are routinely referred to the SickKids and CHEO HIV clinics in Toronto and Ottawa, respectively, for ongoing management. The majority of referrals are from Mount Sinai Hospital and St. Michael's Hospital in Toronto, and the Ottawa General Hospital in Ottawa.

  • Human Immunodeficiency Virus
  • HIV
  • Vertical Infection Transmission
Not Provided
Nevirapine
The patients in this study are newborn infants clinically prescribed combination antiretroviral treatment with nevirapine for prevention of mother-to-child HIV transmission.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
24
February 2016
February 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Newborn infants prescribed combination antiretroviral treatment with nevirapine for prevention of mother-to-child HIV transmission. These infants are routinely referred to the Hospital for Sick Children (SickKids) and Children's Hospital of Eastern Ontario (CHEO) HIV clinics in Toronto and Ottawa, respectively, for ongoing management. The majority of referrals are from Mount Sinai Hospital and St. Michael's Hospital in Toronto, and the Ottawa General Hospital in Ottawa.
  • Voluntary informed consent by the legal guardian

Exclusion Criteria:

  • Infants born prior to 32 weeks gestational age;
  • Infants with life-threatening medical conditions;
  • Infants unable to take oral medication;
  • Infants born to women considered at high risk of harboring nevirapine resistance mutations in whom Kaletra (lopinavir/ritonavir) is a therapeutic option (e.g. term neonates) will be excluded and prescribed Kaletra rather than nevirapine
Both
up to 72 Hours
Yes
Contact: Ari Bitnun, MD 416-813-7654 ext 204649 ari.bitnun@sickkids.ca
Contact: Elaine Lau, PharmD 416-813-6003 elaine.lau@sickkids.ca
Canada
 
NCT02166502
1000029134
No
Ari Bitnun, The Hospital for Sick Children
The Hospital for Sick Children
  • Canadian Foundation for AIDS Research (CANFAR)
  • Children's Hospital of Eastern Ontario
  • St. Michael's Hospital, Toronto
  • Mount Sinai Hospital, Canada
Principal Investigator: Ari Bitnun, MD The Hospital for Sick Children
The Hospital for Sick Children
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP