Trial Outcomes & Findings for Treatment Options for Protease Inhibitor-exposed Children (NCT NCT01146873)

NCT ID: NCT01146873

Last Updated: 2017-03-13

Results Overview

Probability of viral rebound defined as \>=1 HIV RNA measurements \>50 copies/ml using survival analysis by 48 weeks post-randomization.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 300 participants
• Primary outcome timeframe: 48 weeks
• Results posted on: 2017-03-13

Participant Flow

A total of 300 study participants were recruited between June 2010 and October 2012.

Two children discontinued the study prior to randomization.

Participant milestones

Measure	Group 1: Lopinavir/Ritonavir (LPV/r) Participants are assigned to remain on their current LPV/r-based antiretroviral regimen. Ritonavir-boosted lopinavir syrup was given twice per day at 230 mg/m\^2 per dose. Children able to swallow tablets were given 1 tablet twice per day (200 mg lopinavir/50 mg ritonavir) if body surface area was less than 0.9m\^2 or 2 tablets twice per day if body surface area was 0.9m\^2 or higher.	Group 2: Efavirenz (EFV) Participants are assigned to switch to an EFV-based antiretroviral regimen. Efavirenz was prescribed once daily in the evening at 200 mg for weights of 10 kg to 13.9 kg (22-30 lb) and 300mg for weights of 14 kg to 24.9 kg (31-55 lb). Efavirenz was available in 50-mg and 200-mg capsules. If children were unable to swallow capsules, caregivers were shown how to open the capsules and dissolve the contents in water.
Overall Study STARTED	148	150
Overall Study COMPLETED	148	144
Overall Study NOT COMPLETED	0	6

Reasons for withdrawal

Measure	Group 1: Lopinavir/Ritonavir (LPV/r) Participants are assigned to remain on their current LPV/r-based antiretroviral regimen. Ritonavir-boosted lopinavir syrup was given twice per day at 230 mg/m\^2 per dose. Children able to swallow tablets were given 1 tablet twice per day (200 mg lopinavir/50 mg ritonavir) if body surface area was less than 0.9m\^2 or 2 tablets twice per day if body surface area was 0.9m\^2 or higher.	Group 2: Efavirenz (EFV) Participants are assigned to switch to an EFV-based antiretroviral regimen. Efavirenz was prescribed once daily in the evening at 200 mg for weights of 10 kg to 13.9 kg (22-30 lb) and 300mg for weights of 14 kg to 24.9 kg (31-55 lb). Efavirenz was available in 50-mg and 200-mg capsules. If children were unable to swallow capsules, caregivers were shown how to open the capsules and dissolve the contents in water.
Overall Study Transfer out	0	6

Baseline Characteristics

Treatment Options for Protease Inhibitor-exposed Children

Baseline characteristics by cohort

Measure	Group 1: Lopinavir/Ritonavir (LPV/r) n=148 Participants Participants are assigned to remain on their current LPV/r-based antiretroviral regimen. Ritonavir-boosted lopinavir syrup was given twice per day at 230 mg/m\^2 per dose. Children able to swallow tablets were given 1 tablet twice per day (200 mg lopinavir/50 mg ritonavir) if body surface area was less than 0.9m\^2 or 2 tablets twice per day if body surface area was 0.9m\^2 or higher.	Group 2: Efavirenz (EFV) n=150 Participants Participants are assigned to switch to an EFV-based antiretroviral regimen. Efavirenz was prescribed once daily in the evening at 200 mg for weights of 10 kg to 13.9 kg (22-30 lb) and 300mg for weights of 14 kg to 24.9 kg (31-55 lb). Efavirenz was available in 50-mg and 200-mg capsules. If children were unable to swallow capsules, caregivers were shown how to open the capsules and dissolve the contents in water.	Total n=298 Participants Total of all reporting groups
Age, Continuous	4.26 years STANDARD_DEVIATION 1.0 • n=93 Participants	4.28 years STANDARD_DEVIATION 0.9 • n=4 Participants	4.27 years STANDARD_DEVIATION 0.9 • n=27 Participants
Sex: Female, Male Female	80 Participants n=93 Participants	78 Participants n=4 Participants	158 Participants n=27 Participants
Sex: Female, Male Male	68 Participants n=93 Participants	72 Participants n=4 Participants	140 Participants n=27 Participants

PRIMARY outcome

Timeframe: 48 weeks

Probability of viral rebound defined as >=1 HIV RNA measurements >50 copies/ml using survival analysis by 48 weeks post-randomization.

Outcome measures

Measure	Group 1: Lopinavir/Ritonavir (LPV/r) n=148 Participants Participants are assigned to remain on their current LPV/r-based antiretroviral regimen	Group 2: Efavirenz (EFV) n=150 Participants Participants are assigned to switch to an EFV-based antiretroviral regimen
Viral Rebound	0.284 probability of viral rebound Interval 0.211 to 0.357	0.176 probability of viral rebound Interval 0.115 to 0.238

PRIMARY outcome

Timeframe: 48 weeks

Probability of viral failure defined as >= 2 HIV RNA measurements >1000 copies/ml using survival analysis by 48 weeks post-randomization.

Outcome measures

Measure	Group 1: Lopinavir/Ritonavir (LPV/r) n=148 Participants Participants are assigned to remain on their current LPV/r-based antiretroviral regimen	Group 2: Efavirenz (EFV) n=150 Participants Participants are assigned to switch to an EFV-based antiretroviral regimen
Viral Failure	0.020 probability of viral failure Interval 0.002 to 0.043	0.027 probability of viral failure Interval 0.001 to 0.054

SECONDARY outcome

Timeframe: 48 weeks

CD4 Cell Percentage at 48 Weeks After Randomization

Outcome measures

Measure	Group 1: Lopinavir/Ritonavir (LPV/r) n=148 Participants Participants are assigned to remain on their current LPV/r-based antiretroviral regimen	Group 2: Efavirenz (EFV) n=150 Participants Participants are assigned to switch to an EFV-based antiretroviral regimen
CD4 Cell Percentage at 48 Weeks After Randomization	34.7 percentage of cells Interval 33.6 to 35.8	37.5 percentage of cells Interval 36.3 to 38.8

SECONDARY outcome

Timeframe: 40 weeks

Percentage of participants with elevated total cholesterol, elevated LDL, abnormal HDL, or abnormal triglycerides at 40 weeks after randomization

Outcome measures

Measure	Group 1: Lopinavir/Ritonavir (LPV/r) n=148 Participants Participants are assigned to remain on their current LPV/r-based antiretroviral regimen	Group 2: Efavirenz (EFV) n=150 Participants Participants are assigned to switch to an EFV-based antiretroviral regimen
Percentage of Participants With Elevated Total Cholesterol, Elevated LDL, Abnormal HDL, or Abnormal Triglycerides at 40 Weeks After Randomization Elevated total cholesterol	24.8 percentage of participants	13.3 percentage of participants
Percentage of Participants With Elevated Total Cholesterol, Elevated LDL, Abnormal HDL, or Abnormal Triglycerides at 40 Weeks After Randomization Elevated LDL	18.6 percentage of participants	9.8 percentage of participants
Percentage of Participants With Elevated Total Cholesterol, Elevated LDL, Abnormal HDL, or Abnormal Triglycerides at 40 Weeks After Randomization Abnormal HDL	4.8 percentage of participants	4.2 percentage of participants
Percentage of Participants With Elevated Total Cholesterol, Elevated LDL, Abnormal HDL, or Abnormal Triglycerides at 40 Weeks After Randomization Abnormal triglycerides	22.8 percentage of participants	10.5 percentage of participants

SECONDARY outcome

Timeframe: through 48 weeks post randomization

Highest grade ALT after randomization. Grading was determined based on the Division of AIDS (2004) Toxicity Tables to grade adverse reactions. Grading scale: 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (potentially life-threatening).

Outcome measures

Measure	Group 1: Lopinavir/Ritonavir (LPV/r) n=148 Participants Participants are assigned to remain on their current LPV/r-based antiretroviral regimen	Group 2: Efavirenz (EFV) n=150 Participants Participants are assigned to switch to an EFV-based antiretroviral regimen
Highest Grade ALT After Randomization Grade 0	139 number of participants	120 number of participants
Highest Grade ALT After Randomization Grade 1	8 number of participants	16 number of participants
Highest Grade ALT After Randomization Grade 2	0 number of participants	10 number of participants
Highest Grade ALT After Randomization Grade 3	1 number of participants	3 number of participants
Highest Grade ALT After Randomization Grade 4	0 number of participants	1 number of participants

Adverse Events

Group 1: Lopinavir/Ritonavir (LPV/r)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 2: Efavirenz (EFV)

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Group 1: Lopinavir/Ritonavir (LPV/r) n=148 participants at risk Participants are assigned to remain on their current LPV/r-based antiretroviral regimen. Ritonavir-boosted lopinavir syrup was given twice per day at 230 mg/m\^2 per dose. Children able to swallow tablets were given 1 tablet twice per day (200 mg lopinavir/50 mg ritonavir) if body surface area was less than 0.9m\^2 or 2 tablets twice per day if body surface area was 0.9m\^2 or higher	Group 2: Efavirenz (EFV) n=150 participants at risk Participants are assigned to switch to an EFV-based antiretroviral regimen. Efavirenz was prescribed once daily in the evening at 200 mg for weights of 10 kg to 13.9 kg (22-30 lb) and 300mg for weights of 14 kg to 24.9 kg (31-55 lb). Efavirenz was available in 50-mg and 200-mg capsules. If children were unable to swallow capsules, caregivers were shown how to open the capsules and dissolve the contents in water.
Nervous system disorders Seizure	0.00% 0/148 • Through 48 weeks after randomization	1.3% 2/150 • Through 48 weeks after randomization

Other adverse events

Adverse event data not reported

Additional Information

Louise Kuhn, PhD

Columbia University

Phone: 212-305-2398

Email: lk24@cumc.columbia.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER