Human Immunodeficiency VirusNCT02166502
Nevirapine Dosing in Neonates for Prophylaxis of Mother-to-Child-Transmission (MTCT) of HIV Infection
An observational study of Human Immunodeficiency Virus and HIV, run by The Hospital for Sick Children at 2 sites in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 72 hoursHealthy volunteers can take part
- Conditions the study is for
- Human Immunodeficiency Virus, HIV, Vertical Infection Transmission
- How many people
- 27 participants
- Where
- 2 sitesCanada
- Study dates
- Feb 2012to Nov 2015
- Phase
- Observational
- 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 Up to 72 hours
- All sexes
- Healthy volunteers accepted
- Child
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Children's Hospital of Eastern Ontario
Ottawa, Ontario
The Hospital for Sick Children
Toronto, Ontario, M5G1X8
About this study
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.
Read the 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.
- Keywords
- pediatric, HIV, prevention, prophylaxis, nevirapine
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Nevirapine | The patients in this study are newborn infants clinically prescribed combination antiretroviral treatment with nevirapine for prevention of mother-to-child HIV transmission. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of nevirapine trough (Cmin) plasma levels that are above or below the target range for prophylaxis
Measured: Weeks 1, 2, and 4
Secondary outcomes (5)
Final dose of nevirapine
Final dose of nevirapine required to achieve target plasma trough concentrations at week 4
Measured: Week 4
Derived pharmacokinetic parameters
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)
Measured: Week 4
Association between nevirapine levels and incidence of adverse effects
Number of adverse events among patients with therapeutic vs. supratherapeutic nevirapine levels
Measured: Weeks 1, 2 and 4
Association between patient characteristics and differences in nevirapine levels
Patient characteristics that may explain differences in nevirapine levels including chronologic and gestational age, weight, and ethnic background.
Measured: Baseline, Week 1, 2 and 4
Rate of vertical transmission of HIV
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2014 (estimated)
- Study startFeb 2012
- Primary completionMay 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Human Immunodeficiency VirusStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Foundation for AIDS Research (CANFAR), Children's Hospital of Eastern Ontario, Unity Health Toronto, Mount Sinai Hospital, Canada
- Responsible party
- Principal investigator, Ari Bitnun, The Hospital for Sick Children
- Investigators
- Ari Bitnun, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02166502
- Sponsor's protocol ID
- 1000029134
- Status last verified
- Nov 2015
- First submitted
- 5 Jun 2014
- Last updated
- 18 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nevirapine Dosing in Neonates for Prophylaxis of Mother-to-Child-Transmission (MTCT) of HIV Infection
- ClinicalTrials.gov ID
- NCT02166502
- Acronym / sponsor ID
- 1000029134
- Keywords
- pediatric, HIV, prevention, prophylaxis, nevirapine
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Canadian Foundation for AIDS Research (CANFAR), Children's Hospital of Eastern Ontario, Unity Health Toronto, Mount Sinai Hospital, Canada
- Study start
- Feb 2012
- Primary completion
- May 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 18 Jun 2014 (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 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.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nevirapine | – | –The patients in this study are newborn infants clinically prescribed combination antiretroviral treatment with nevirapine for prevention of mother-to-child HIV transmission. |
Who may qualify
- Ages
- Up to 72 hours
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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.
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Proportion of nevirapine trough (Cmin) plasma levels that are above or below the target range for prophylaxis
Time frame: Weeks 1, 2, and 4
5 secondary outcomes
Final dose of nevirapine
Time frame: Week 4
Derived pharmacokinetic parameters
Time frame: Week 4
Association between nevirapine levels and incidence of adverse effects
Time frame: Weeks 1, 2 and 4
Association between patient characteristics and differences in nevirapine levels
Time frame: Baseline, Week 1, 2 and 4
Rate of vertical transmission of HIV
Time frame: 18 months
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 18 Nov 2015.
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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.
Ari Bitnun, MD principal investigator
The Hospital for Sick Children
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Human Immunodeficiency Virus and HIV, run by The Hospital for Sick Children at 2 sites in Canada.
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 2 inclusion and 4 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 18 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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.
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.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Nov 2015.