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Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya

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ClinicalTrials.gov Identifier: NCT00427297
Recruitment Status : Terminated (There is no longer equipoise. DSMB recommended termination.)
First Posted : January 29, 2007
Results First Posted : August 27, 2018
Last Update Posted : August 27, 2018
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Grace John-Stewart, University of Washington

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)
Drug: d4T/3TC/NVP (stavudine/lamivudine/nevirapine)
Drug: AZT/3TC/ABC (zidovudine/lamivudine/abacavir)
Drug: d4T/3TC/ABC (stavudine/lamivudine/abacavir)
Drug: ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir)
Drug: ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz)
Drug: ABC/3TC/NVP (abacavir/lamivudine/nevirapine)
Enrollment 34
Recruitment Details  
Pre-assignment Details  
Arm/Group Title NVP-containing NVP-sparing
Hide Arm/Group Description

Infants randomized to this arm will receive nevirapine-containing HAART regimen

AZT/3TC/NVP (zidovudine/lamivudine/nevirapine): First line regimen

d4T/3TC/NVP (stavudine/lamivudine/nevirapine): First line regimen

ABC/3TC/NVP (abacavir/lamivudine/nevirapine): First line regimen

Infants randomized to this arm will receive nevirapine-sparing HAART

AZT/3TC/ABC (zidovudine/lamivudine/abacavir): First line regimen

d4T/3TC/ABC (stavudine/lamivudine/abacavir): First line regimen For children who have anaemia(Hb of<8g/dl), AZT will be substituted for d4T.

ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir): Second line regimen

ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz): Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.

Period Title: Overall Study
Started 17 17
Completed 17 17
Not Completed 0 0
Arm/Group Title NVP-containing NVP-sparing Total
Hide Arm/Group Description

Infants randomized to this arm will receive nevirapine-containing HAART regimen

AZT/3TC/NVP (zidovudine/lamivudine/nevirapine): First line regimen

d4T/3TC/NVP (stavudine/lamivudine/nevirapine): First line regimen

ABC/3TC/NVP (abacavir/lamivudine/nevirapine): First line regimen

Infants randomized to this arm will receive nevirapine-sparing HAART

AZT/3TC/ABC (zidovudine/lamivudine/abacavir): First line regimen

d4T/3TC/ABC (stavudine/lamivudine/abacavir): First line regimen For children who have anaemia(Hb of<8g/dl), AZT will be substituted for d4T.

ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir): Second line regimen

ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz): Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.

Total of all reporting groups
Overall Number of Baseline Participants 17 17 34
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Months
Number Analyzed 17 participants 17 participants 34 participants
7
(6 to 10)
8
(6 to 10)
7
(6 to 10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 17 participants 34 participants
Female
8
  47.1%
7
  41.2%
15
  44.1%
Male
9
  52.9%
10
  58.8%
19
  55.9%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Kenya Number Analyzed 17 participants 17 participants 34 participants
17
 100.0%
17
 100.0%
34
 100.0%
CD4%  
Median (Inter-Quartile Range)
Unit of measure:  Percentage of cells
Number Analyzed 17 participants 17 participants 34 participants
22
(14 to 29)
18
(13 to 25)
21.5
(13 to 27)
1.Primary Outcome
Title Incidence of Mortality
Hide Description Death during follow-up
Time Frame 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was conducted at DSMB termination of study with 15.6 person-years of follow-up time in the cohort overall; 8.5 person-years in NVP-containing and 7.1 person-years in NVP-sparing arm.
Arm/Group Title NVP-containing NVP-sparing
Hide Arm/Group Description:

Infants randomized to this arm will receive nevirapine-containing HAART regimen

AZT/3TC/NVP (zidovudine/lamivudine/nevirapine): First line regimen

d4T/3TC/NVP (stavudine/lamivudine/nevirapine): First line regimen

ABC/3TC/NVP (abacavir/lamivudine/nevirapine): First line regimen

Infants randomized to this arm will receive nevirapine-sparing HAART

AZT/3TC/ABC (zidovudine/lamivudine/abacavir): First line regimen

d4T/3TC/ABC (stavudine/lamivudine/abacavir): First line regimen For children who have anaemia(Hb of<8g/dl), AZT will be substituted for d4T.

ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir): Second line regimen

ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz): Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.

Overall Number of Participants Analyzed 17 17
Measure Type: Count of Participants
Unit of Measure: Participants
4
  23.5%
5
  29.4%
2.Primary Outcome
Title Immunologic Failure
Hide Description Immunologic treatment failure was defined as CD4% dropping below 15%, after a previous result greater than or equal to 15% (following along WHO Guidelines).
Time Frame 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
15.6 person years of follow-up overall at time of DSMB closure of study
Arm/Group Title NVP-containing NVP-sparing
Hide Arm/Group Description:

Infants randomized to this arm will receive nevirapine-containing HAART regimen

AZT/3TC/NVP (zidovudine/lamivudine/nevirapine): First line regimen

d4T/3TC/NVP (stavudine/lamivudine/nevirapine): First line regimen

ABC/3TC/NVP (abacavir/lamivudine/nevirapine): First line regimen

Infants randomized to this arm will receive nevirapine-sparing HAART

AZT/3TC/ABC (zidovudine/lamivudine/abacavir): First line regimen

d4T/3TC/ABC (stavudine/lamivudine/abacavir): First line regimen For children who have anaemia(Hb of<8g/dl), AZT will be substituted for d4T.

ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir): Second line regimen

ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz): Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.

Overall Number of Participants Analyzed 12 13
Measure Type: Count of Participants
Unit of Measure: Participants
2
  16.7%
1
   7.7%
3.Primary Outcome
Title Viral Failure
Hide Description Virologic treatment failure was defined as follow-up (at least 24 weeks after enrollment date) viral load > 400 copies.
Time Frame 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
15.6 person years of follow-up overall at time of DSMB closure of study
Arm/Group Title NVP-containing NVP-sparing
Hide Arm/Group Description:

Infants randomized to this arm will receive nevirapine-containing HAART regimen

AZT/3TC/NVP (zidovudine/lamivudine/nevirapine): First line regimen

d4T/3TC/NVP (stavudine/lamivudine/nevirapine): First line regimen

ABC/3TC/NVP (abacavir/lamivudine/nevirapine): First line regimen

Infants randomized to this arm will receive nevirapine-sparing HAART

AZT/3TC/ABC (zidovudine/lamivudine/abacavir): First line regimen

d4T/3TC/ABC (stavudine/lamivudine/abacavir): First line regimen For children who have anaemia(Hb of<8g/dl), AZT will be substituted for d4T.

ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir): Second line regimen

ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz): Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.

Overall Number of Participants Analyzed 8 5
Measure Type: Count of Participants
Unit of Measure: Participants
2
  25.0%
2
  40.0%
4.Secondary Outcome
Title Incidence of Severe Adverse Events (Excluding Mortality)
Hide Description [Not Specified]
Time Frame 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
15.6 person-years of follow-up overall at time of DSMB closure of study
Arm/Group Title NVP-containing NVP-sparing
Hide Arm/Group Description:

Infants randomized to this arm will receive nevirapine-containing HAART regimen

AZT/3TC/NVP (zidovudine/lamivudine/nevirapine): First line regimen

d4T/3TC/NVP (stavudine/lamivudine/nevirapine): First line regimen

ABC/3TC/NVP (abacavir/lamivudine/nevirapine): First line regimen

Infants randomized to this arm will receive nevirapine-sparing HAART

AZT/3TC/ABC (zidovudine/lamivudine/abacavir): First line regimen

d4T/3TC/ABC (stavudine/lamivudine/abacavir): First line regimen For children who have anaemia(Hb of<8g/dl), AZT will be substituted for d4T.

ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir): Second line regimen

ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz): Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.

Overall Number of Participants Analyzed 17 17
Measure Type: Number
Unit of Measure: event
21 6
Time Frame 2 years
Adverse Event Reporting Description 15.6 person years overall of follow-up at time of DSMB closure of study
 
Arm/Group Title NVP-containing NVP-sparing
Hide Arm/Group Description

NVP-containing (AZT/3TC/NVP; d4T/3TC/NVP; or ABC/3TC/NVP) antiretroviral triple combination therapy.

Second-line regimens based on the WHO pediatric treatment guidelines, 2006.

NVP-sparing (AZT/3TC/LPV/r; or d4T/3TC/LPV/r1) antiretroviral triple combination therapy.

Second-line regimens based on the WHO pediatric treatment guidelines, 2006.

All-Cause Mortality
NVP-containing NVP-sparing
Affected / at Risk (%) Affected / at Risk (%)
Total   4/17 (23.53%)   5/17 (29.41%) 
Show Serious Adverse Events Hide Serious Adverse Events
NVP-containing NVP-sparing
Affected / at Risk (%) Affected / at Risk (%)
Total   4/17 (23.53%)   3/17 (17.65%) 
Blood and lymphatic system disorders     
Severe anemia  2/17 (11.76%)  0/17 (0.00%) 
Gastrointestinal disorders     
Hyperamylasemia   0/17 (0.00%)  1/17 (5.88%) 
Hepatobiliary disorders     
Hepatotoxicity   2/17 (11.76%)  1/17 (5.88%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia or respiratory   4/17 (23.53%)  1/17 (5.88%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
NVP-containing NVP-sparing
Affected / at Risk (%) Affected / at Risk (%)
Total   13/17 (76.47%)   15/17 (88.24%) 
Gastrointestinal disorders     
Gastroenteritis   4/17 (23.53%)  4/17 (23.53%) 
Nervous system disorders     
Milestone regression   1/17 (5.88%)  1/17 (5.88%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia   9/17 (52.94%)  5/17 (29.41%) 
Skin and subcutaneous tissue disorders     
Rash   3/17 (17.65%)  7/17 (41.18%) 
Indicates events were collected by systematic assessment
The study team suggested discontinuation of the trial and the DSMB concurred based on slow accrual and based on new data that emerged after the RCT was initiated which made the trial question less relevant.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Grace John-Stewart
Organization: University of Washington
Phone: 206 5434278
EMail: gjohn@uw.edu
Responsible Party: Grace John-Stewart, University of Washington
ClinicalTrials.gov Identifier: NCT00427297     History of Changes
Other Study ID Numbers: STUDY00002049
2R01HD023412-16 ( U.S. NIH Grant/Contract )
06-1886-D 02
First Submitted: January 22, 2007
First Posted: January 29, 2007
Results First Submitted: June 29, 2018
Results First Posted: August 27, 2018
Last Update Posted: August 27, 2018