Equivalence of Boosted Atazanavir Based Regimens and Currently Effective HAART Regimens

• Sponsor: Phoenix Children's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00940771
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 86.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The hypothesis for this study is whether a treatment regimen containing Atazanavir in combination with Ritonavir will work as well as other regimens containing a protease inhibitor and/or a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) at controlling HIV disease in children who are HIV+ and have high cholesterol or high triglycerides. . In this study, children who have high cholesterol or high triglycerides as a result of their HIV medicines, will have the PI or NNRTI in their medication regimen changed to Atazanavir, which is a PI in combination with a low dose of Ritonavir (another PI). Atazanavir has been shown in adults to result in lower cholesterol and triglycerides than other PI's and NNRTI's. The dose of Atazanavir and Ritonavir will be according to the Package Insert for this drug that is FDA approved for children. They will continue taking the other medications from the pre-study regimen. Children will take study drug for 24 weeks, and will be able to continue study drug after the study using commercially available drug. Lab tests and a physical exam will be undertaken at 4 weeks, 12 weeks and 24 weeks after starting study drug to determine how effective the new drug is and to monitor for possible side effects.

Condition or Disease	Intervention/Treatment	Phase
Pediatric HIV; HIV Infections	Drug: Boosted Atazanavir	Phase 4

Detailed Description

The primary objective of this study is to determine if Atazanavir and Ritonavir together will be as effective as the child's previous regimen in keeping the level of virus in the blood stream at such a low level it can't be found and whether that combination will be as effective as the previous regimen in keeping the infection fighting cells in the blood at the same level.

Secondary objectives will be:

• To determine if cholesterol and triglyceride levels drop in children switching to Atazanavir and Ritonavir from other medication regimens.

• To evaluate if Atazanavir and Ritonavir result in an increase in patient satisfaction and patient reported adherence and a decrease in symptoms related to medication side effects.

Inclusion Criteria are:

• On the same medication regimen at least 3 months

• Weight equal to or greater than 25kg

• Able to swallow pills or willing to learn

• Have a parent or guardian willing and able to sign informed consent

• Not be taking a medication which interacts with Atazanavir

• Not be currently taking Sustiva

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Equivalence of Boosted Atazanavir Based Regimens and Currently Effective HAART Regimens With Other PI's/NNRTI's in HIV+ Children and Adolescents With Elevated Lipid Levels
• Actual Study Start Date: Aug 26, 2009
• Actual Primary Completion Date: Oct 16, 2013
• Actual Study Completion Date: Nov 23, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: boosted Atazanavir Boosted Atazanavir was switched for the PI or NNRTI in the patients regimen	Drug: Boosted Atazanavir; Boosted Atazanavir, once a day dose adjusted for child's weight for 6 months.; Other Names: Reyataz

Outcome Measures

Primary Outcome Measures

1. Non-fasting Cholesterol [4 Weeks, 12 weeks, 24 weeks]

2. Non-fasting Triglycerides [4 weeks, 12 weeks, 24 weeks]

Secondary Outcome Measures

1. Viral Load [4 weeks, 12 weeks, 24 weeks]

   Number of participants with undetectable viral load

2. CD4 Count [4 Weeks, 12 weeks, 24 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV positive children with elevated lipid levels

• on stable HAART for at least 3 months (defined to be on the same regimen with viral load < 1000 for 6 months prior to baseline visit).

• Weight equal to or greater than 25kg

• Able to swallow pills or willing to learn

Exclusion Criteria:

• Patients with underlying hepatitis B or C viral infections

• Previously demonstrated clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of Reyataz® (atazanavir).

• Taking other medications that are highly dependent on CYP3A or UGT1A1 for clearance

• Ergot medicines: dihydroergotamine, ergonovine, ergotamine, and methylergonovine such as Cafergot®, Migranal®, D.H.E. 45®, ergotrate maleate, Methergine®, and others (used for migraine headaches).

• Orap® (pimozide, used for Tourette's disorder).

• Propulsid® (cisapride, used for certain stomach problems).

• Triazolam, also known as Halcion® (used for insomnia).

• Midazolam, also known as Versed® (used for sedation), when taken by mouth.

• Camptosar® (irinotecan, used for cancer).

• Crixivan® (indinavir, used for HIV infection).

• Cholesterol-lowering medicines Mevacor® (lovastatin) or Zocor® (simvastatin).

• Rifampin (also known as Rimactane®, Rifadin®, Rifater®, or Rifamate®).

• St. John's wort (Hypericum perforatum), an herbal product sold as a dietary supplement,

• Viramune® (nevirapine, used for HIV infection).

• Vfend® (voriconazole).

• Patients with grade 3 or higher elevations in transaminases (> 10 X ULN)

• Women of Childbearing Potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period.

• Women who are pregnant or breastfeeding.

• Women with a positive pregnancy test.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016

Sponsors and Collaborators

• Phoenix Children's Hospital
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Janice Piatt, MD, Phoenix Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janice Piatt, Medical Director, Bill Holt Clinic, Phoenix Children's Hospital
• ClinicalTrials.gov Identifier: NCT00940771
• Other Study ID Numbers: PCH 09-004
• First Posted: Jul 16, 2009
• Last Update Posted: Apr 20, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Janice Piatt, Medical Director, Bill Holt Clinic, Phoenix Children's Hospital: HIV; Lipids; Atazanavir; Pediatric; treatment experienced
• Additional relevant MeSH terms: HIV Infections; Atazanavir Sulfate

Study Results

Participant Flow

Recruitment Details	Pediatric patients with elevated cholesterol were recruited from a Pediatric HIV Clinic between April 8, 2009 and May 1, 2013.

Arm/Group Title	Boosted Atazanavir
Arm/Group Description	Boosted atazanavir was switched for the PI or NNRTI in the patients regimen Boosted atazanavir, once a day dose adjusted for child's weight for 6 months.
Period Title: Pre-Entry
STARTED	10
COMPLETED	10
NOT COMPLETED	0
Period Title: Pre-Entry
STARTED	10
COMPLETED	10
NOT COMPLETED	0
Period Title: Pre-Entry
STARTED	10
COMPLETED	10
NOT COMPLETED	0
Period Title: Pre-Entry
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Boosted Atazanavir
Arm/Group Description	Boosted atazanavir was switched for the PI or NNRTI in the patients regimen Boosted Atazanavir: Boosted atazanavir, once a day dose adjusted for child's weight for 6 months.
Overall Participants	10
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	9.5
Sex: Female, Male (Count of Participants)
Female	2 20%
Male	8 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 20%
Not Hispanic or Latino	8 80%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 10%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 40%
White	5 50%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%
CD4 (cells/uL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/uL]	1233.1 (473.8)
Viral Load (copies/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [copies/ml]	2.3 (7.3)
Cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	214.3 (31.6)
Triglycerides (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	288.5 (253.9)

Outcome Measures

1. Primary Outcome

Title	Non-fasting Cholesterol
Time Frame	4 Weeks, 12 weeks, 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Boosted Atazanavir
Arm/Group Description	Boosted atazanavir was switched for the PI or NNRTI in the patients regimen Boosted atazanavir, once a day dose adjusted for child's weight for 6 months.
Measure Participants	10
Week 4	187.2 (30.0)
Week 12	178.5 (38.1)
Week 24	181.5 (29.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Boosted Atazanavir
	Comments
	Type of Statistical Test	Other
	Comments	Friedman's Test
Statistical Test of Hypothesis	p-Value	.006
	Comments
	Method	Friedman's Test
	Comments	3 degrees of freedom.
Method of Estimation	Estimation Parameter	Chi Square
	Estimated Value	12.3
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Boosted Atazanavir
	Comments	Nul lHypothesis that there is no difference between specific time points.
	Type of Statistical Test	Other
	Comments	Post Hoc testing Post hoc Wilcoxon Signed Rank tests
Statistical Test of Hypothesis	p-Value	.007
	Comments
	Method	Wilcoxon Signed Rank
	Comments	Z=-2.701

2. Primary Outcome

Title	Non-fasting Triglycerides
Time Frame	4 weeks, 12 weeks, 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Boosted Atazanavir
Arm/Group Description	Boosted atazanavir was switched for the PI or NNRTI in the patients regimen Boosted atazanavir, once a day dose adjusted for child's weight for 6 months.
Measure Participants	10
Week 4	240.5 (107.2)
Week 12	195.5 (93.8)
Week 24	193.3 (106.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Boosted Atazanavir
	Comments
	Type of Statistical Test	Other
	Comments	Friedman's test with 3 df
Statistical Test of Hypothesis	p-Value	.356
	Comments
	Method	Friedman's Test
	Comments	3 degrees of freedom

3. Secondary Outcome

Title	Viral Load
Description	Number of participants with undetectable viral load
Time Frame	4 weeks, 12 weeks, 24 weeks

Outcome Measure Data

Analysis Population Description

Number of patients with undetectable viral load

Arm/Group Title	Boosted Atazanavir
Arm/Group Description	Boosted atazanavir was switched for the PI or NNRTI in the patients regimen Boosted atazanavir, once a day dose adjusted for child's weight for 6 months.
Measure Participants	10
Week 4	10 100%
Week 12	9 90%
Week 24	9 90%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Boosted Atazanavir
	Comments	The null hypothesis was that there was a difference. We were looking for no difference between before and after switch.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.801
	Comments
	Method	Friedman's test
	Comments	3 degrees of freedom
Method of Estimation	Estimation Parameter	Chi-square
	Estimated Value	1.0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	1.0 is the actual calculated Chi-X value, not the p value.

4. Secondary Outcome

Title	CD4 Count
Time Frame	4 Weeks, 12 weeks, 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Boosted Atazanavir
Arm/Group Description	Boosted atazanavir was switched for the PI or NNRTI in the patients regimen Boosted atazanavir, once a day dose adjusted for child's weight for 6 months.
Measure Participants	10
Week 4	1214.3 (476.8)
Week 12	1151.9 (442.7)
Week 24	1120.0 (413.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Boosted Atazanavir
	Comments
	Type of Statistical Test	Other
	Comments	Friedman's test
Statistical Test of Hypothesis	p-Value	.075
	Comments	a priori threshold for statistical significance 0.05
	Method	Friedman's test
	Comments	3 degrees of freedom

Adverse Events

Time Frame	24 weeks
Adverse Event Reporting Description	The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events V 1.0, December 2004, Clarification August 2009 was used to grade labs and symptoms that were reported at week 4, week 12 and week 24 visits.
Arm/Group Title	Boosted Atazanavir
Arm/Group Description	Boosted atazanavir was switched for the PI or NNRTI in the patients regimen Boosted atazanavir, once a day dose adjusted for child's weight for 6 months.
All Cause Mortality
	Boosted Atazanavir
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Boosted Atazanavir
	Affected / at Risk (%)	# Events
Total	1/10 (10%)
Infections and infestations
Pansinusitis	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Boosted Atazanavir
	Affected / at Risk (%)	# Events
Total	2/10 (20%)
Blood and lymphatic system disorders
Pain, neck and face	1/10 (10%)	1
Gastrointestinal disorders
Vomiting	1/10 (10%)	1
Laboratory Abnormality	1/10 (10%)	3
General disorders
Fever	2/10 (20%)	2
Respiratory, thoracic and mediastinal disorders
Pain, throat	1/10 (10%)	1
cough	1/10 (10%)	1

Limitations/Caveats

Small sample size Non fasting lipid levels Large variety of prior treatment regimens

More Information

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.