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
  Purpose

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.


Condition Phase
Human Immunodeficiency Virus
HIV
Vertical Infection Transmission
Phase 3

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Nevirapine Dosing in Neonates for Prophylaxis of Mother-to-Child-Transmission (MTCT) of HIV Infection

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 24
Study Start Date: February 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Nevirapine
The patients in this study are newborn infants clinically prescribed combination antiretroviral treatment with nevirapine for prevention of mother-to-child HIV transmission.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 72 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

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.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02166502

Contacts
Contact: Ari Bitnun, MD 416-813-7654 ext 204649 ari.bitnun@sickkids.ca
Contact: Elaine Lau, PharmD 416-813-6003 elaine.lau@sickkids.ca

Locations
Canada, Ontario
Children's Hospital of Eastern Ontario Recruiting
Ottawa, Ontario, Canada
Contact: Jason Brophy, MD         
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Ari Bitnun, MD    416-813-7654 ext 204649    ari.bitnun@sickkids.ca   
Contact: Elaine Lau, PharmD    416-813-6003    elaine.lau@sickkids.ca   
Principal Investigator: Ari Bitnun, MD, MSc         
Sub-Investigator: Elaine Lau, PharmD, MSc         
Sponsors and Collaborators
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
Investigators
Principal Investigator: Ari Bitnun, MD The Hospital for Sick Children
  More Information

No publications provided

Responsible Party: Ari Bitnun, Staff Physician, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT02166502     History of Changes
Other Study ID Numbers: 1000029134
Study First Received: June 5, 2014
Last Updated: June 14, 2014
Health Authority: Canada: Health Canada

Keywords provided by The Hospital for Sick Children:
pediatric
HIV
prevention
prophylaxis
nevirapine

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Immunologic Deficiency Syndromes
Infection
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Nevirapine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014