Effects of Pitavastatin on Lipid Profiles in HIV-infected Patients With Dyslipidemia and Receiving Atazanavir/Ritonavir

• Sponsor: Ramathibodi Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02442700
• Collaborator: (none)
• Enrollment: 24
• Arms: 2
• Duration (Months): 8

Study Details

Study Description

Brief Summary

Dyslipidemia as a risk factor for cardiovascular disease (CVD) is an increasing problem in HIV-infected patients who are on antiretroviral therapy especially protease inhibitors including atazanavir. Pitavastatin is a new HMG-CoA reductase inhibitor with lesser drug-drug interactions and demonstrable efficacy in decreasing lipid levels in non HIV-infected individuals. The study was conducted as a randomized, double-blind, crossover study comparing the safety and efficacy of pitavastatin versus placebo in HIV-infected patients with dyslipidemia and receiving atazanavir/ritonavir. Patients were randomized to receive either placebo or pitavastatin for 12 weeks, underwent a 2-week washout period, and then were given the other treatment for an additional 12 weeks. Patients were observed for lipid profiles including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL); and the side effects including clinical and laboratory (serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine phosphokinase (CPK)). The follow-up visits were every 4 weeks until the end of the study.

Condition or Disease	Intervention/Treatment	Phase
HIV; Dyslipidemia	Drug: pitavastatin; Drug: placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Pitavastatin on Lipid Profiles in HIV-infected Patients With Dyslipidemia and Receiving Atazanavir/Ritonavir: A Randomized, Double-blind, Crossover Study
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment sequence A, B Treatment visits were seperated by a 2-week washout period. Treatment A = administration pitavastatin for 12 weeks; Treatment B = administration placebo for 12 weeks	Drug: pitavastatin; Treatment A = administration pitavastatin for 12 weeks; Other Names: Livalo ; Drug: placebo; Treatment B = administration placebo for 12 weeks
Experimental: Treatment sequence B, A Treatment visits were seperated by a 2-week washout period. Treatment B = adminstration placebo for 12 weeks; Treatment A = adminstration pitavastatin for 12 weeks	Drug: pitavastatin; Treatment A = administration pitavastatin for 12 weeks; Other Names: Livalo ; Drug: placebo; Treatment B = administration placebo for 12 weeks

Outcome Measures

Primary Outcome Measures

1. Efficacy of Pitavastatin in HIV-infected Patients With Dyslipidemia and Receiving Atazanavir/Ritonavir [12 weeks]

   Efficacy was measured by level of TC, TG, LDL, and HDL that decreased after pitavastatin treatment. Pitavastatin was considered efficient when it could decrease TC, TG, LDL, or HDL significantly compared to placebo.

Secondary Outcome Measures

1. Safety of Pitavastatin in HIV-infected Patients [12 weeks]

   Safety clinical was defined by FDA; grade 1 mild symptoms; grade 2 moderate symptoms with limiting age-appropriate IADL; grade 3 severe symptoms with limiting self-care ADL, But not immediately life-threatening; grade 4 life-threatening consequences; and grade 5 death related to adverse event. Safety laboratory evaluation was determined safe if AST, ALT, and/or CPK level was not increased significantly comparing pitavastatin to placebo.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• aged ≥18 years

• able to provide informed consent

• had confirmed HIV infection

• on ART including atazanavir 300 mg and ritonavir 100 mg each day in the regimens that were not changed within 12 weeks before the randomization

• patients who had cholesterol level between 200 and 500 and LDL between 130 and 400 mg/dL without any lipid-lowering agent or discontinued the lipid-lowering agent at least 1 month prior to randomization

Exclusion Criteria:

• had the history of pitavastatin and/or the constituent of the drugs allergy

• known history of myocardial infarction and/or ischemic stroke within 1 month prior to the randomization that would be endangered if we stopped the previous lipid-lowering agent before the enrollment

• abnormal AST and ALT with level ≥5 times in asymptomatic patients or ≥3 times of upper normal limit (UNL) in symptomatic patients

• pregnancy or breastfeeding

• on cyclosporine which had major drug interactions with pitavastatin

• patients who denied to join the study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Ramathibodi Hospital

Investigators

• Principal Investigator: Asita Wongprikorn, Ramathibodi Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Asita Wongprikorn, Ramathibodi Hospital, Ramathibodi Hospital
• ClinicalTrials.gov Identifier: NCT02442700
• Other Study ID Numbers: Ramathibodi Hospital 01-57-18
• First Posted: May 13, 2015
• Last Update Posted: Oct 10, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Asita Wongprikorn, Ramathibodi Hospital, Ramathibodi Hospital: HIV-infected patients with dyslipidemia and receiving atazanavir/ritonavir
• Additional relevant MeSH terms: Dyslipidemias; Pitavastatin

Study Results

Participant Flow

Pre-assignment Detail	All subjects received all 2 treatments in a randomly assigned order. The treatments were: Treatment A: pitavastatin; Treatment B: placebo. The sequences were Treatments AB, BA.

Arm/Group Title	Treatment A, B	Treatment B, A
Arm/Group Description	Treatment visits were separated by a 2-week washout period. Treatment A = administration pitavastatin for 12 weeks; Treatment B = administration placebo for 12 weeks	Treatment visits were separated by a 2-week washout period. Treatment B = administration placebo for 12 weeks; Treatment A = administration pitavastatin for 12 weeks
Period Title: First 12 Weeks
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: First 12 Weeks
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Treatment A, B	Treatment B, A	Total
Arm/Group Description	Treatment visits were separated by a 2-week washout period. Treatment A = administration pitavastatin for 12 weeks; Treatment B = administration placebo for 12 weeks	Treatment visits were separated by a 2-week washout period. Treatment B = administration placebo for 12 weeks; Treatment A = administration pitavastatin for 12 weeks	Total of all reporting groups
Overall Participants	12	12	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.6 (10.6)	46.7 (6.8)	48.1 (1.8)
Sex: Female, Male (Count of Participants)
Female	4 33.3%	6 50%	10 41.7%
Male	8 66.7%	6 50%	14 58.3%
Body mass index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	23.8 (2.7)	22.5 (3.4)	23.2 (3.1)
Underlying conditions (participants) [Number]
No	4 33.3%	8 66.7%	12 50%
Dyslipidemia	4 33.3%	2 16.7%	6 25%
Chronic hepatitis B and C virus infection	2 16.7%	2 16.7%	4 16.7%
Others	2 16.7%	0 0%	2 8.3%
Cardiovascular risk factors (participants) [Number]
<2	7 58.3%	11 91.7%	18 75%
> or equal to 2	5 41.7%	1 8.3%	6 25%
Baseline Creatinine (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	0.9 (0.2)	0.9 (0.2)	0.9 (0.2)
Baseline Fasting blood sugar (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	100.8 (10.1)	97.1 (10.5)	98.9 (10.2)
Baseline CD4 cell counts (cells/mm3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/mm3]	641.9 (196.5)	718.1 (181.2)	680 (189)
HIV viral load <40 copies/mL (participants) [Number]
Number [participants]	12 100%	11 91.7%	23 95.8%
Duration of ATV/r use (months) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [months]	42	36	36
Antiretroviral regimens combined with ATV/r (participants) [Number]
TDF + FTC/3TC	5 41.7%	6 50%	11 45.8%
TDF + other NRTIs (exclude FTC/3TC)	2 16.7%	2 16.7%	4 16.7%
No TDF in backbone	5 41.7%	4 33.3%	9 37.5%

Outcome Measures

1. Primary Outcome

Title	Efficacy of Pitavastatin in HIV-infected Patients With Dyslipidemia and Receiving Atazanavir/Ritonavir
Description	Efficacy was measured by level of TC, TG, LDL, and HDL that decreased after pitavastatin treatment. Pitavastatin was considered efficient when it could decrease TC, TG, LDL, or HDL significantly compared to placebo.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Treatment visits were separated by a 2-week washout period. Treatment A = administration pitavastatin for 12 weeks; Treatment B = administration placebo for 12 weeks	Treatment visits were separated by a 2-week washout period. Treatment B = administration placebo for 12 weeks; Treatment A = administration pitavastatin for 12 weeks
Measure Participants	24	24
TC at baseline	239.9	257.6
TG at baseline	282	350
LDL at baseline	144.7	146.3
HDL at baseline	43	44.8
TC at 4 weeks after treatment	201.3	246.6
TG at 4 weeks after treatment	246.5	292.5
LDL at 4 weeks after treatment	111.6	142.5
HDL at 4 weeks after treatment	43.5	43.5
TC at 8 weeks after treatment	202.3	255.2
TG at 8 weeks after treatment	250.8	334
LDL at 8 weeks after treatment	111.5	145.1
HDL at 8 weeks after treatment	44.9	43.7
TC at 12 weeks after treatment	207	246.3
TG at 12 weeks after treatment	351.3	279.1
LDL after 12 weeks of treatment	113.2	145.6
HDL after 12 weeks of treatment	45.3	44.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Safety of Pitavastatin in HIV-infected Patients
Description	Safety clinical was defined by FDA; grade 1 mild symptoms; grade 2 moderate symptoms with limiting age-appropriate IADL; grade 3 severe symptoms with limiting self-care ADL, But not immediately life-threatening; grade 4 life-threatening consequences; and grade 5 death related to adverse event. Safety laboratory evaluation was determined safe if AST, ALT, and/or CPK level was not increased significantly comparing pitavastatin to placebo.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Treatment visits were separated by a 2-week washout period. Treatment A = administration pitavastatin for 12 weeks; Treatment B = administration placebo for 12 weeks	Treatment visits were separated by a 2-week washout period. Treatment B = administration placebo for 12 weeks; Treatment A = administration pitavastatin for 12 weeks
Measure Participants	24	24
AST at baseline	38.2	36.3
ALT at baseline	64.6	58.9
AST at 12 weeks after treatment	39.5	40.75
ALT at 12 weeks after treatment	64.2	72.5

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Treatment A		Treatment B
Arm/Group Description	Treatment A = administration pitavastatin for 12 weeks		Treatment B = administration placebo for 12 weeks
All Cause Mortality
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)

Limitations/Caveats

LImitation of this study is we did not adjust pitavastatin dosage according to lipid profiles,thus mean value of TC could not be lower than 200 mg/dL.

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.