Multicountry, Multicenter Post-Marketing Observational Study of Clinical, Biological and Virological Outcomes, Compliance and Tolerability of Kaletra® in Routine Clinical Use

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01379703

Acronym

KaleEAST

Enrollment

2288

Registered

2011-06-23

Start date

2004-02-29

Completion date

2010-02-28

Last updated

2011-10-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV-1 Patients

Keywords

HIV-1 infected patients, Protease inhibitor, Kaletra®

Brief summary

KaleEAST is a non-interventional, post-marketing observational study (PMOS) in which lopinavir/ritonavir is prescribed in the usual manner in accordance with the terms of the local marketing authorization with regards to dose, population and indication. No additional procedures (other than the standard of care) are to be applied to the patients. The KaleEAST PMOS was conducted in a prospective, single-arm, multicountry, multicenter format. The study was carried out in two (2) parts: the first part was initiated in 2004 with the lopinavir/ritonavir capsule formulation, the second part started in 2006 after the lopinavir/ritonavir tablets had become available in the participating countries. The aim of this post-marketing observational study was to obtain further data on clinical, biological, and virological outcomes, compliance and tolerability of Kaletra®-containing regimen during routine clinical use in the participating countries.

Detailed description

As this study is observational in nature, subject follow-up was not specified by the protocol but was left to the judgment of each physician within the 18 months period, which defines the survey for each participant. For indicative purposes, follow-up of each participant should enable approximately 7 visits during this period. These visits will take place at average intervals of 3 months, apart from the first visit following inclusion (usually at the end of the first treatment month) and apart from visits required because of intercurrent events. Participant visits were assigned as follows: Baseline/Day 0 (start of lopinavir/ritonavir treatment), Month 1 (day 1 to day 45), Month 3 (day 46 to day 136), Month 6 (day 137 to day 228), Month 9 (day 229 to day 319), Month 12 (day 320 to day 410), Month 15 (day 411 to day 501), Month 18 (day 502 to day 593). Each participant is planned to be observed during his/her lopinavir/ritonavir capsule containing treatment regimen for a maximum period of 18 months, and each participant is planned to be observed during his/her lopinavir/ritonavir tablet containing treatment regimen for a maximum period of 9 months.

Interventions

None listed

Study design

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

2 Years to No maximum

Healthy volunteers

Inclusion criteria

Patients infected by HIV-1 infection who are either: * Antiretroviral treatment (ART) naive or * Had failed or had been intolerant to one previous combined antiretroviral treatment (cART), not including a Protease inhibitor (PI) (first-line pretreated without a Protease inhibitor) or * Had failed or had been intolerant to one previous antiretroviral treatment ART, including one Protease inhibitor (first-line pretreated with a Protease Inhibitor). A ritonavir-boosted Protease inhibitor PI is considered as treatment with one Protease inhibitor PI.

Exclusion criteria

* Treatment with drugs at risk for interactions with lopinavir/ritonavir * Uncontrolled AIDS defining disease * Two or more previous Protease inhibitors (PIs) * Participation in another study or clinical trial

Design outcomes

Primary

Measure	Time frame	Description
Laboratory Parameter Lipids	Baseline, 9 months, 18 months	A blood lipid panel consisting of total cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels was performed at baseline and scheduled study visits. Normal ranges are based on the standards for individual facilities in each country.
Viral Load	Baseline	Viral load is a direct measure of the viral burden by providing a count of the number of HIV-RNA copies in blood (plasma). The number of HIV-RNA copies in the blood was measured at baseline.
Laboratory Parameter Blood Glucose	Baseline, 9 months, 18 months	Blood glucose laboratory values were assessed at baseline and scheduled study visits. Normal ranges are based on the standards for individual facilities in each country.
Laboratory Parameter Transaminases	Baseline, 9 months, 18 months	Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) laboratory values were assessed at baseline and scheduled study visits. Normal ranges are based on the standards for individual facilities in each country.
CD4 Count	Baseline	CD4 lymphocyte count is a measure of a participant's immunologic health. Participants' CD4-positive (CD4+) T-lymphocyte counts were assessed by measuring the number of CD4+ cells at baseline.
Changes in CD4 Count	Baseline to 1 month	Increases in CD4 count are a biomarker for antiretroviral treatment effectiveness in restoring immunologic function. Changes in participants' CD4-positive (CD4+) T-lymphocyte counts were assessed by measuring the change from Baseline in the number of CD4+ cells at scheduled study visits.

Secondary

Measure	Time frame	Description
Compliance With Lopinavir/Ritonavir	9 months	Participants reported whether they had missed doses of their antiretroviral treatment.
Adverse Events Observed on Treatment With Lopinavir/Ritonavir.	18 months	Total number of adverse events with causal relationship (rated by Investigator as probably or possibly related) to lopinavir/ritonavir treatment. All serious adverse events and non serious adverse events (0.2% or greater frequency) are summarized in the Reported Adverse Events section of this record.
Reasons for Discontinuation of Lopinavir/Ritonavir	9 months	For participants who discontinued lopinavir/ritonavir treatment, the reasons for discontinuation are provided.

Countries

Czechia, Georgia, Israel, Latvia, Lithuania, Poland, Romania, Russia, Serbia, Slovakia, Slovenia, Ukraine

Participant flow

Recruitment details

The study was carried out in two parts. The first part was initiated in 2004 with the lopinavir/ritonavir capsule formulation (Part I) and the second part (Part II) started in 2006 after the tablet formulation became available in participating countries.

Participants by arm

Arm	Count
Total Study Population HIV-1 infected participants who received lopinavir/ritonavir (any formulation) during any part of the study.	2,288
Total	2,288

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
9 Months Through 18 Months	Adverse Event	0	6	0
9 Months Through 18 Months	Fatigue	0	1	0
9 Months Through 18 Months	Lost to Follow-up	0	178	0
9 Months Through 18 Months	Patient Noncompliance	0	4	0
9 Months Through 18 Months	Reason Unknown	0	23	0
9 Months Through 18 Months	Treatment failure	0	5	0
9 Months Through 18 Months	Tuberculosis/TB treatment	0	2	0
9 Months Through 18 Months	Withdrawal by Subject	0	11	0
Study Start Through 9 Months	Adverse Event	0	14	10
Study Start Through 9 Months	Increased triglycerides	0	1	0
Study Start Through 9 Months	Lost to Follow-up	2	61	104
Study Start Through 9 Months	Medication not available	0	2	1
Study Start Through 9 Months	Patient Noncompliance	0	0	1
Study Start Through 9 Months	Poor general condition	0	1	0
Study Start Through 9 Months	Reason unknown	2	31	24
Study Start Through 9 Months	Treatment Failure	0	2	2
Study Start Through 9 Months	Tuberculosis/TB treatment	0	4	0
Study Start Through 9 Months	Withdrawal by Subject	0	6	1

Baseline characteristics

Characteristic	Total Study Population
Age Continuous	32.6 years STANDARD_DEVIATION 11
Region of Enrollment Czech Republic	107 participants
Region of Enrollment Georgia	10 participants
Region of Enrollment Israel	139 participants
Region of Enrollment Latvia	18 participants
Region of Enrollment Lithuania	3 participants
Region of Enrollment Poland	381 participants
Region of Enrollment Romania	422 participants
Region of Enrollment Russian Federation	644 participants
Region of Enrollment Serbia	149 participants
Region of Enrollment Slovakia	26 participants
Region of Enrollment Slovenia	123 participants
Region of Enrollment Ukraine	266 participants
Sex/Gender, Customized Data not reported	2 Participants
Sex/Gender, Customized Female	867 Participants
Sex/Gender, Customized Male	1419 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	109 / 2,288	77 / 1,206	34 / 1,016
serious Total, serious adverse events	46 / 2,288	22 / 1,206	22 / 1,016

Outcome results

Primary

CD4 Count

CD4 lymphocyte count is a measure of a participant's immunologic health. Participants' CD4-positive (CD4+) T-lymphocyte counts were assessed by measuring the number of CD4+ cells at baseline.

Time frame: Baseline

Population: Mean CD4 count is based on number of participants in each group who had CD4 count results at Baseline.

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	CD4 Count	Mean CD4 count	229.9 cells per mm³	Standard Deviation 194.2
Capsule Formulation	CD4 Count	Mean CD4 count	208.8 cells per mm³	Standard Deviation 187.2
Tablet Formulation	CD4 Count	Mean CD4 count	246.8 cells per mm³	Standard Deviation 194.8

Primary

Changes in CD4 Count

Increases in CD4 count are a biomarker for antiretroviral treatment effectiveness in restoring immunologic function. Changes in participants' CD4-positive (CD4+) T-lymphocyte counts were assessed by measuring the change from Baseline in the number of CD4+ cells at scheduled study visits.

Time frame: Baseline to 1 month

Population: Change from baseline analysis is based on participants with CD4 count results available at 1 month.

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	Changes in CD4 Count	Mean CD4 count at 1 month	288.7 cells per mm³	Standard Deviation 185.1
Total Study Population	Changes in CD4 Count	Change in CD4 count	60.3 cells per mm³	Standard Deviation 137.4
Capsule Formulation	Changes in CD4 Count	Mean CD4 count at 1 month	277.1 cells per mm³	Standard Deviation 195.7
Capsule Formulation	Changes in CD4 Count	Change in CD4 count	54.9 cells per mm³	Standard Deviation 158.3
Tablet Formulation	Changes in CD4 Count	Mean CD4 count at 1 month	296.1 cells per mm³	Standard Deviation 172.1
Tablet Formulation	Changes in CD4 Count	Change in CD4 count	70.6 cells per mm³	Standard Deviation 113.8

Primary

Changes in CD4 Count

Time frame: Baseline to 3 months

Population: Change from baseline analysis is based on participants with CD4 count results available at 3 months.

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	Changes in CD4 Count	Mean CD4 count at 3 months	323.9 cells per mm³	Standard Deviation 219.3
Total Study Population	Changes in CD4 Count	Change in CD4 count	94.5 cells per mm³	Standard Deviation 162.9
Capsule Formulation	Changes in CD4 Count	Mean CD4 count at 3 months	310.1 cells per mm³	Standard Deviation 227.9
Capsule Formulation	Changes in CD4 Count	Change in CD4 count	97.7 cells per mm³	Standard Deviation 188.7
Tablet Formulation	Changes in CD4 Count	Mean CD4 count at 3 months	332.4 cells per mm³	Standard Deviation 206.7
Tablet Formulation	Changes in CD4 Count	Change in CD4 count	93.2 cells per mm³	Standard Deviation 123.9

Primary

Changes in CD4 Count

Time frame: Baseline to 6 months

Population: Change from baseline analysis is based on participants with CD4 count results available at 6 months.

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	Changes in CD4 Count	Mean CD4 count at 6 months	361.5 cells per mm³	Standard Deviation 248.9
Total Study Population	Changes in CD4 Count	Change in CD4 count	124.4 cells per mm³	Standard Deviation 197.6
Capsule Formulation	Changes in CD4 Count	Mean CD4 count at 6 months	333.4 cells per mm³	Standard Deviation 219.8
Capsule Formulation	Changes in CD4 Count	Change in CD4 count	117.1 cells per mm³	Standard Deviation 182.5
Tablet Formulation	Changes in CD4 Count	Mean CD4 count at 6 months	382.0 cells per mm³	Standard Deviation 271.7
Tablet Formulation	Changes in CD4 Count	Change in CD4 count	131.6 cells per mm³	Standard Deviation 216

Primary

Changes in CD4 Count

Time frame: Baseline to 9 months

Population: Change from baseline analysis is based on participants with CD4 count results available at 9 months.

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	Changes in CD4 Count	Mean CD4 count at 9 months	384.1 cells per mm³	Standard Deviation 221.4
Total Study Population	Changes in CD4 Count	Change in CD4 count	151.5 cells per mm³	Standard Deviation 174.4
Capsule Formulation	Changes in CD4 Count	Mean CD4 count at 9 months	363.5 cells per mm³	Standard Deviation 222.2
Capsule Formulation	Changes in CD4 Count	Change in CD4 count	144.8 cells per mm³	Standard Deviation 191.7
Tablet Formulation	Changes in CD4 Count	Mean CD4 count at 9 months	395.0 cells per mm³	Standard Deviation 209
Tablet Formulation	Changes in CD4 Count	Change in CD4 count	156.0 cells per mm³	Standard Deviation 151.5

Primary

Changes in CD4 Count

Time frame: Baseline to 12 months

Population: Only participants receiving lopinavir/ritonavir capsules were planned to be followed past 9 months. Change from baseline analysis is based on participants receiving capsule formulation with CD4 count results available at 12 months.

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	Changes in CD4 Count	Mean CD4 count at 12 months	392.0 cells per mm³	Standard Deviation 216.5
Total Study Population	Changes in CD4 Count	Change in CD4 count	170.4 cells per mm³	Standard Deviation 201.7

Primary

Changes in CD4 Count

Time frame: Baseline to 15 months

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	Changes in CD4 Count	Mean CD4 count at 15 months	412.6 cells per mm³	Standard Deviation 240.5
Total Study Population	Changes in CD4 Count	Change in CD4 count	194.8 cells per mm³	Standard Deviation 228.5

Primary

Changes in CD4 Count

Time frame: Baseline to 18 months

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	Changes in CD4 Count	Mean CD4 count at 18 months	429.7 cells per mm³	Standard Deviation 249.4
Total Study Population	Changes in CD4 Count	Change in CD4 count	222.2 cells per mm³	Standard Deviation 228.7

Primary

Laboratory Parameter Blood Glucose

Blood glucose laboratory values were assessed at baseline and scheduled study visits. Normal ranges are based on the standards for individual facilities in each country.

Time frame: Baseline, 9 months, 18 months

Population: Analysis was based on participants with laboratory values at each time point. Only participants receiving lopinavir/ritonavir capsules were planned to be followed after 9 months.

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	Laboratory Parameter Blood Glucose	Baseline	4.87 millimoles per liter	Standard Deviation 2.05
Total Study Population	Laboratory Parameter Blood Glucose	18 months	NA millimoles per liter	—
Total Study Population	Laboratory Parameter Blood Glucose	9 months	4.92 millimoles per liter	Standard Deviation 1.42
Capsule Formulation	Laboratory Parameter Blood Glucose	18 months	5.07 millimoles per liter	Standard Deviation 2.64
Capsule Formulation	Laboratory Parameter Blood Glucose	Baseline	4.89 millimoles per liter	Standard Deviation 2.83
Capsule Formulation	Laboratory Parameter Blood Glucose	9 months	4.87 millimoles per liter	Standard Deviation 1.38
Tablet Formulation	Laboratory Parameter Blood Glucose	18 months	NA millimoles per liter	—
Tablet Formulation	Laboratory Parameter Blood Glucose	9 months	4.99 millimoles per liter	Standard Deviation 1.49
Tablet Formulation	Laboratory Parameter Blood Glucose	Baseline	4.85 millimoles per liter	Standard Deviation 0.86

Primary

Laboratory Parameter Lipids

A blood lipid panel consisting of total cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels was performed at baseline and scheduled study visits. Normal ranges are based on the standards for individual facilities in each country.

Time frame: Baseline, 9 months, 18 months

Population: Analysis was based on participants with laboratory values at each time point. Only participants receiving lopinavir/ritonavir capsules were planned to be followed past 9 months.

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	Laboratory Parameter Lipids	Total Cholesterol - Baseline	4.37 millimoles per liter	Standard Deviation 1.5
Total Study Population	Laboratory Parameter Lipids	Total Cholesterol - 9 months	4.96 millimoles per liter	Standard Deviation 1.81
Total Study Population	Laboratory Parameter Lipids	Total Cholesterol - 18 Months	NA millimoles per liter	—
Total Study Population	Laboratory Parameter Lipids	HDL Cholesterol - Baseline	1.39 millimoles per liter	Standard Deviation 0.84
Total Study Population	Laboratory Parameter Lipids	HDL Cholesterol - 9 months	1.53 millimoles per liter	Standard Deviation 0.98
Total Study Population	Laboratory Parameter Lipids	HDL Cholesterol - 18 months	NA millimoles per liter	—
Total Study Population	Laboratory Parameter Lipids	LDL Cholesterol - Baseline	2.50 millimoles per liter	Standard Deviation 1.07
Total Study Population	Laboratory Parameter Lipids	LDL Cholesterol - 9 months	2.73 millimoles per liter	Standard Deviation 1.07
Total Study Population	Laboratory Parameter Lipids	LDL Cholesterol - 18 months	NA millimoles per liter	—
Total Study Population	Laboratory Parameter Lipids	Triglycerides - Baseline	1.65 millimoles per liter	Standard Deviation 1.06
Total Study Population	Laboratory Parameter Lipids	Triglycerides - 9 months	2.20 millimoles per liter	Standard Deviation 1.46
Total Study Population	Laboratory Parameter Lipids	Triglycerides - 18 months	NA millimoles per liter	—
Capsule Formulation	Laboratory Parameter Lipids	Triglycerides - 18 months	2.13 millimoles per liter	Standard Deviation 1.35
Capsule Formulation	Laboratory Parameter Lipids	Total Cholesterol - Baseline	4.48 millimoles per liter	Standard Deviation 1.68
Capsule Formulation	Laboratory Parameter Lipids	LDL Cholesterol - Baseline	2.87 millimoles per liter	Standard Deviation 1.1
Capsule Formulation	Laboratory Parameter Lipids	LDL Cholesterol - 18 months	3.09 millimoles per liter	Standard Deviation 1.14
Capsule Formulation	Laboratory Parameter Lipids	Total Cholesterol - 9 months	5.07 millimoles per liter	Standard Deviation 2.36
Capsule Formulation	Laboratory Parameter Lipids	HDL Cholesterol - 18 months	2.04 millimoles per liter	Standard Deviation 1.94
Capsule Formulation	Laboratory Parameter Lipids	Triglycerides - 9 months	2.21 millimoles per liter	Standard Deviation 1.49
Capsule Formulation	Laboratory Parameter Lipids	Total Cholesterol - 18 Months	5.01 millimoles per liter	Standard Deviation 1.29
Capsule Formulation	Laboratory Parameter Lipids	LDL Cholesterol - 9 months	3.11 millimoles per liter	Standard Deviation 1.18
Capsule Formulation	Laboratory Parameter Lipids	HDL Cholesterol - 9 months	2.08 millimoles per liter	Standard Deviation 1.64
Capsule Formulation	Laboratory Parameter Lipids	HDL Cholesterol - Baseline	2.17 millimoles per liter	Standard Deviation 1.45
Capsule Formulation	Laboratory Parameter Lipids	Triglycerides - Baseline	1.66 millimoles per liter	Standard Deviation 1.11
Tablet Formulation	Laboratory Parameter Lipids	HDL Cholesterol - Baseline	1.19 millimoles per liter	Standard Deviation 0.44
Tablet Formulation	Laboratory Parameter Lipids	HDL Cholesterol - 9 months	1.32 millimoles per liter	Standard Deviation 0.53
Tablet Formulation	Laboratory Parameter Lipids	Triglycerides - Baseline	1.64 millimoles per liter	Standard Deviation 1.04
Tablet Formulation	Laboratory Parameter Lipids	HDL Cholesterol - 18 months	NA millimoles per liter	—
Tablet Formulation	Laboratory Parameter Lipids	LDL Cholesterol - Baseline	2.29 millimoles per liter	Standard Deviation 1.02
Tablet Formulation	Laboratory Parameter Lipids	LDL Cholesterol - 9 months	2.51 millimoles per liter	Standard Deviation 0.95
Tablet Formulation	Laboratory Parameter Lipids	Triglycerides - 9 months	2.17 millimoles per liter	Standard Deviation 1.44
Tablet Formulation	Laboratory Parameter Lipids	Total Cholesterol - Baseline	4.28 millimoles per liter	Standard Deviation 1.35
Tablet Formulation	Laboratory Parameter Lipids	Total Cholesterol - 9 months	4.89 millimoles per liter	Standard Deviation 1.25
Tablet Formulation	Laboratory Parameter Lipids	LDL Cholesterol - 18 months	NA millimoles per liter	—
Tablet Formulation	Laboratory Parameter Lipids	Total Cholesterol - 18 Months	NA millimoles per liter	—
Tablet Formulation	Laboratory Parameter Lipids	Triglycerides - 18 months	NA millimoles per liter	—

Primary

Laboratory Parameter Transaminases

Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) laboratory values were assessed at baseline and scheduled study visits. Normal ranges are based on the standards for individual facilities in each country.

Time frame: Baseline, 9 months, 18 months

Population: Analysis was based on participants with laboratory values at each time point. Only participants receiving lopinavir/ritonavir capsules were planned to be followed past 9 months.

Arm	Measure	Group	Value (MEAN)	Dispersion
Total Study Population	Laboratory Parameter Transaminases	AST - Baseline	38.9 international units per liter	Standard Deviation 37.1
Total Study Population	Laboratory Parameter Transaminases	AST - 9 months	35.2 international units per liter	Standard Deviation 33
Total Study Population	Laboratory Parameter Transaminases	AST - 18 months	NA international units per liter	—
Total Study Population	Laboratory Parameter Transaminases	ALT - Baseline	41.0 international units per liter	Standard Deviation 40.3
Total Study Population	Laboratory Parameter Transaminases	ALT - 9 months	39.8 international units per liter	Standard Deviation 52.5
Total Study Population	Laboratory Parameter Transaminases	ALT - 18 months	NA international units per liter	—
Capsule Formulation	Laboratory Parameter Transaminases	ALT - 18 months	42.0 international units per liter	Standard Deviation 44.8
Capsule Formulation	Laboratory Parameter Transaminases	AST - Baseline	36.8 international units per liter	Standard Deviation 32.1
Capsule Formulation	Laboratory Parameter Transaminases	ALT - Baseline	39.6 international units per liter	Standard Deviation 38.7
Capsule Formulation	Laboratory Parameter Transaminases	ALT - 9 months	40.8 international units per liter	Standard Deviation 44.8
Capsule Formulation	Laboratory Parameter Transaminases	AST - 9 months	34.8 international units per liter	Standard Deviation 29.6
Capsule Formulation	Laboratory Parameter Transaminases	AST - 18 months	36.4 international units per liter	Standard Deviation 30.8
Tablet Formulation	Laboratory Parameter Transaminases	AST - 9 months	36.0 international units per liter	Standard Deviation 36.9
Tablet Formulation	Laboratory Parameter Transaminases	AST - 18 months	NA international units per liter	—
Tablet Formulation	Laboratory Parameter Transaminases	ALT - 18 months	NA international units per liter	—
Tablet Formulation	Laboratory Parameter Transaminases	ALT - Baseline	42.6 international units per liter	Standard Deviation 42.6
Tablet Formulation	Laboratory Parameter Transaminases	AST - Baseline	41.4 international units per liter	Standard Deviation 42.4
Tablet Formulation	Laboratory Parameter Transaminases	ALT - 9 months	39.0 international units per liter	Standard Deviation 60.3

Primary