Trial Outcomes & Findings for Arterial Function and Atherosclerosis in Essential Thrombocythemia (NCT NCT03828422)
NCT ID: NCT03828422
Last Updated: 2021-11-04
Results Overview
4-year change carotid artery in Beta-stiffness Index measured in JAK2 V617F positive ET patients in comparison to healthy control subjects. All measurements were performed by echo-tracking ultrasound of the common carotid artery. Echo-tracking of the common carotid artery wall was used to assess arterial stiffness expressed by the β-stiffness index. Measurement swere done at the common carotid artery 2 cm proximal to the bulb on both sides. The β-stiffness index was calculated as: β = ln (P\_max / P\_min) / \[(D\_max - D\_min / D\_min)\] (P\_max = the systolic blood pressure, P\_min = the diastolic pressure; D\_max = the maximum arterial diameter and D\_min = the minimal arterial diameter). In the adult population, the values of β range from 4 - 10 and increase with age. A larger value of β means increased arterial stiffness, i.e., a worse outcome.
COMPLETED
82 participants
From Baseline (in 2014-2015) to Year 4 (in 2018-2019)
2021-11-04
Participant Flow
a single tertiary medical centre
had documented or clinically suspected atherosclerotic vascular disease
Participant milestones
| Measure |
Patients With Essential Thrombocythemia
* essential thrombocythemia with JAK2 V617F positive mutation
* patients from the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* examined twice, the first time in the years 2014-2015 and for the second time in the years 2018-2019
* blood for laboratory tests
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
Control Group
* the control group is selected among healthy employees of the University Medical Centre Ljubljana and their relatives
* they are matched with the patient group for age and sex distribution and classical risk factors for cardiovascular disease
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* blood for laboratory tests
* examined twice, the first time in the years 2014-2015 and for the second time the in years 2018-2019
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
|---|---|---|
|
Overall Study
STARTED
|
40
|
42
|
|
Overall Study
COMPLETED
|
36
|
38
|
|
Overall Study
NOT COMPLETED
|
4
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Patients With Essential Thrombocythemia
n=36 Participants
* essential thrombocythemia with JAK2 V617F positive mutation
* patients from the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* examined twice, the first time in the years 2014-2015 and for the second time in the years 2018-2019
* blood for laboratory tests
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
Control Group
n=38 Participants
* the control group is selected among healthy employees of the University Medical Centre Ljubljana and their relatives
* they are matched with the patient group for age and sex distribution and classical risk factors for cardiovascular disease
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* blood for laboratory tests
* examined twice, the first time in the years 2014-2015 and for the second time the in years 2018-2019
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
Total
n=74 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55 years
STANDARD_DEVIATION 13 • n=36 Participants
|
59 years
STANDARD_DEVIATION 12 • n=38 Participants
|
57 years
STANDARD_DEVIATION 13 • n=74 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=36 Participants
|
24 Participants
n=38 Participants
|
48 Participants
n=74 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=36 Participants
|
14 Participants
n=38 Participants
|
26 Participants
n=74 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Slovenia
|
36 participants
n=36 Participants
|
38 participants
n=38 Participants
|
74 participants
n=74 Participants
|
PRIMARY outcome
Timeframe: From Baseline (in 2014-2015) to Year 4 (in 2018-2019)4-year change carotid artery in Beta-stiffness Index measured in JAK2 V617F positive ET patients in comparison to healthy control subjects. All measurements were performed by echo-tracking ultrasound of the common carotid artery. Echo-tracking of the common carotid artery wall was used to assess arterial stiffness expressed by the β-stiffness index. Measurement swere done at the common carotid artery 2 cm proximal to the bulb on both sides. The β-stiffness index was calculated as: β = ln (P\_max / P\_min) / \[(D\_max - D\_min / D\_min)\] (P\_max = the systolic blood pressure, P\_min = the diastolic pressure; D\_max = the maximum arterial diameter and D\_min = the minimal arterial diameter). In the adult population, the values of β range from 4 - 10 and increase with age. A larger value of β means increased arterial stiffness, i.e., a worse outcome.
Outcome measures
| Measure |
Patients With Essential Thrombocythemia
n=36 Participants
* essential thrombocythemia with JAK2 V617F positive mutation
* patients from the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* examined twice, the first time in the years 2014-2015 and for the second time in the years 2018-2019
* blood for laboratory tests
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
Control Group
n=38 Participants
* the control group is selected among healthy employees of the University Medical Centre Ljubljana and their relatives
* they are matched with the patient group for age and sex distribution and classical risk factors for cardiovascular disease
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* blood for laboratory tests
* examined twice, the first time in the years 2014-2015 and for the second time the in years 2018-2019
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
|---|---|---|
|
Carotid Artery Stiffness (Expressed by Beta-stiffness Index ) in JAK2 V617F Positive ET Patients in Comparison to Healthy Control Subjects in a 4-year Period (From Baseline to Year 4).
|
1.95 index
Standard Deviation 2.18
|
0.22 index
Standard Deviation 1.99
|
PRIMARY outcome
Timeframe: From Baseline (in 2014-2015) to Year 4 (in 2018-2019)4-year change in carotid artery pulse wave velocity (PWV) measured in JAK2 V617F positive ET patients in comparison to healthy control subjects. All measurements were performed by echo-tracking ultrasound of the common carotid artery. Measurements were done at the common carotid artery 2 cm proximal to the bulb on both sides. PWV was calculated from the beta stiffness index (β, for description see above), as follows: PWV = √ ((β x P\_min) / 2ρ)); ρ = 1050 kg/m³. PWV increases with arterial stiffness, a larger value means a worse outcome. PWV in adults ranges from 3 m/s to 12 m/s; values are strongly age dependent.
Outcome measures
| Measure |
Patients With Essential Thrombocythemia
n=36 Participants
* essential thrombocythemia with JAK2 V617F positive mutation
* patients from the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* examined twice, the first time in the years 2014-2015 and for the second time in the years 2018-2019
* blood for laboratory tests
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
Control Group
n=38 Participants
* the control group is selected among healthy employees of the University Medical Centre Ljubljana and their relatives
* they are matched with the patient group for age and sex distribution and classical risk factors for cardiovascular disease
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* blood for laboratory tests
* examined twice, the first time in the years 2014-2015 and for the second time the in years 2018-2019
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
|---|---|---|
|
Carotid Artery Stiffness (Expressed by the Pulse Wave Velocity) in JAK2 V617F Positive ET Patients in Comparison to Healthy Control Subjects in a 4-year Period (From Baseline to Year 4).
|
0.72 m/s
Standard Deviation 0.92
|
0.08 m/s
Standard Deviation 0.72
|
PRIMARY outcome
Timeframe: From Baseline (in 2014-2015) to Year 4 (in 2018-2019)Change in carotid plaque score (i.e., the number of carotid artery segments with detected plaques, reported on a scale from 0-6) in a 4 year observation period. A carotid plaque score 0 means that the common carotid, internal carotid and exteranal carotid artery on both sides are free from plaques. A score of 6 means that the common carotid, internal carotid and external carotid artery on both sides have plaques detected by ultrasound.
Outcome measures
| Measure |
Patients With Essential Thrombocythemia
n=36 Participants
* essential thrombocythemia with JAK2 V617F positive mutation
* patients from the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* examined twice, the first time in the years 2014-2015 and for the second time in the years 2018-2019
* blood for laboratory tests
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
Control Group
n=38 Participants
* the control group is selected among healthy employees of the University Medical Centre Ljubljana and their relatives
* they are matched with the patient group for age and sex distribution and classical risk factors for cardiovascular disease
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* blood for laboratory tests
* examined twice, the first time in the years 2014-2015 and for the second time the in years 2018-2019
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
|---|---|---|
|
Change of Carotid Artery Plaque Score in JAK2 V617F Positive ET Patients in Comparison to Healthy Control Subjects in a 4-year Period.
|
0 score on a scale
Interval 0.0 to 0.0
|
0 score on a scale
Interval 0.0 to 0.0
|
PRIMARY outcome
Timeframe: From Baseline (in 2014-2015) to Year 4 (in 2018-2019)Change in the Agatston coronary artery calcium score in a 4 year observation period. Agatston score denotes the number of coronary artery calcifications weighted for the intensity of calcification. Grading of coronary artery disease (CAD) based od Agatston score goes as follows: no CAD = score 0, minimal CAD = score 1-10, mild CAD = score 11-100, moderate CAD = score 101-400, svere CAD = score \> 400.
Outcome measures
| Measure |
Patients With Essential Thrombocythemia
n=36 Participants
* essential thrombocythemia with JAK2 V617F positive mutation
* patients from the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* examined twice, the first time in the years 2014-2015 and for the second time in the years 2018-2019
* blood for laboratory tests
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
Control Group
n=38 Participants
* the control group is selected among healthy employees of the University Medical Centre Ljubljana and their relatives
* they are matched with the patient group for age and sex distribution and classical risk factors for cardiovascular disease
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* blood for laboratory tests
* examined twice, the first time in the years 2014-2015 and for the second time the in years 2018-2019
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
|---|---|---|
|
Change of Coronary Calcium Burden in JAK2 V617F Positive ET Patients in Comparison to Healthy Control Subjects in a 4-year Period.
|
0 units on a scale
Interval 0.0 to 15.85
|
1.6 units on a scale
Interval 0.0 to 14.1
|
PRIMARY outcome
Timeframe: From Baseline (in 2014-2015) to Year 4 (in 2018-2019)4-year change in Reactive Hyperemia Index (RHI) and 4-year change Augmentation Index (AI). RHI was calculated by the formula: RHI = (A/B) / (C/D) where A is the post-occlusion pulse wave amplitude (PWA) of the occluded hand, B the baseline PWA of the occluded hand, C the post-occlusion PWA of the contralateral hand, and D the baseline PWA of the contralateral hand. A higher RHI means better endothelial function (= good outcome). RHI in patients ranges from1-3. Arbitrarily, normal RHI is defined as =\> 1.67, and abnormal RHI as RHI =\< 1.66. The AI was determined from the shape of the arterial pulse wave by the EndoPAT 2000 software which distinguished between the primary pulse wave (P1) and the reflected pulse wave (P2) by the formula: AI = ((P2-P1)/P1) x 100. The results were normalized to a heart rate of 75/min. A higher AI means greater arterial stiffness (= bad outcome). AI \>0.4 is abnormal.
Outcome measures
| Measure |
Patients With Essential Thrombocythemia
n=36 Participants
* essential thrombocythemia with JAK2 V617F positive mutation
* patients from the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* examined twice, the first time in the years 2014-2015 and for the second time in the years 2018-2019
* blood for laboratory tests
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
Control Group
n=38 Participants
* the control group is selected among healthy employees of the University Medical Centre Ljubljana and their relatives
* they are matched with the patient group for age and sex distribution and classical risk factors for cardiovascular disease
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* blood for laboratory tests
* examined twice, the first time in the years 2014-2015 and for the second time the in years 2018-2019
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
|---|---|---|
|
Change of Digital Endothelial Function, Expressed as Reactive Hyperemia Index and Augmentation Index (AI), in JAK2 V617F Positive ET Patients in Comparison to Healthy Control Subjects in a 4-year Period.
Reactive Hyperemia Index (RHI)
|
-0.02 units on a scale
Standard Deviation 0.77
|
-0.26 units on a scale
Standard Deviation 0.89
|
|
Change of Digital Endothelial Function, Expressed as Reactive Hyperemia Index and Augmentation Index (AI), in JAK2 V617F Positive ET Patients in Comparison to Healthy Control Subjects in a 4-year Period.
Augmentation Index (AI)
|
3.56 units on a scale
Standard Deviation 16.88
|
0.46 units on a scale
Standard Deviation 20.19
|
PRIMARY outcome
Timeframe: At baseline (in 2014- 2015) and at the second visit (in 2018-2019)Population: The control group was not included in the comparison because they lack JAK2 V617F mutation as they are healthy subjects with no mutation. We examine the association between mutation burden (where the mutation is necessary) and coronary calcium burden.
Change in JAK2 V617F mutation burden in the 4-year observation period. Ipsogen JAK2 MutaQuant Kit, Qiagen (USA) was used for the detection of JAK2 V617F mutation and quantification of its burden in genomic DNA, which was extracted from granulocytes in peripheral blood. Real-time quantitative polymerase chain reaction (qPCR) was used with double-dye oligonucleotide hydrolysis principle. The JAK2 V617F burden was defined as the percentage of JAK2 V617F mutated alleles in total genomic DNA.
Outcome measures
| Measure |
Patients With Essential Thrombocythemia
n=36 Participants
* essential thrombocythemia with JAK2 V617F positive mutation
* patients from the Department of Haematology at University Medical Centre Ljubljana, Slovenia, who were diagnosed with JAK2 V617F positive ET between 2011 and 2014
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* examined twice, the first time in the years 2014-2015 and for the second time in the years 2018-2019
* blood for laboratory tests
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
Control Group
* the control group is selected among healthy employees of the University Medical Centre Ljubljana and their relatives
* they are matched with the patient group for age and sex distribution and classical risk factors for cardiovascular disease
* no personal history of clinically manifest atherosclerotic vascular disease (myocardial infarction, angina pectoris, peripheral arterial disease, aortic disease, transient ischemic attack or ischemic stroke)
* all signed the informed consent
* blood for laboratory tests
* examined twice, the first time in the years 2014-2015 and for the second time the in years 2018-2019
* imaging and functional examination: ultrasound examination, EndoPat plethysmography, coronary artery calcium scanning
imaging
|
|---|---|---|
|
The JAK2 V617F Mutation Burden in Patients With JAK2 V617F Positive ET.
JAK2 V617F mutation burden at baseline
|
29.95 percentage of mutant allele
Interval 7.32 to 43.33
|
—
|
|
The JAK2 V617F Mutation Burden in Patients With JAK2 V617F Positive ET.
JAK2 V617F mutation burden at the second visit
|
11.60 percentage of mutant allele
Interval 0.0 to 26.63
|
—
|
Adverse Events
Patients With Essential Thrombocythemia
Control Group
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
dr. Aleš Blinc, MD, PhD
University Medical Centre Ljubljana
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place