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出境医 / 临床实验 / Tonometry and Duplex Ultrasound to Predict AAA Progression and CV Events in Aneurysm Patients (1-2-3 Trial)

Tonometry and Duplex Ultrasound to Predict AAA Progression and CV Events in Aneurysm Patients (1-2-3 Trial)

Study Description
Brief Summary:

Abdominal aortic aneurysm (AAA) is a common vascular disease and associated with risk of rupture, but also with a high cardiovascular (CV) event rate. A key difficulty in AAA is predicting these life-threatening complications, highlighting the need to explore the potential of novel techniques. Both progression of AAA and CV events are strongly linked to vascular health. In 2013, the SMART risk score is developed to calculate the risk of the patients for recurrent vascular events based on clinical characteristics. Recently, a novel, easy to perform, non-invasive test of endothelial function (the carotid artery reactivity (CAR) test), reflecting target organ damage, has recently been introduced. The CAR is a simple, quick (5-min), non-invasive test that uses ultrasound to examine the carotid artery in response to sympathetic stimulation by placing one hand in cold water. This test shows strong agreement with both coronary and aortic responses to sympathetic stimulation and predicted CV events in patients with peripheral arterial disease.

The aim of this prospective 2-year follow-up study is to investigate the predictive capacity of the CAR-test in comparison to the SMART risk score for the development of cardiovascular events in patients with an abdominal aortic aneurysm who have not yet reached the treatment threshold. This could aid clinical decision making in the need for (surgical) intervention, but also alter (drug) treatment to reduce risk of cardiovascular events. Secondary objectives are to investigate the predictive capacity of the CAR-test for progression of the abdominal aortic aneurysm, and to evaluate QoL scores in patients under surveillance for AAA. The aim is to provide insight if these scores can help clinical decision making.


Condition or disease Intervention/treatment
Abdominal Aortic Aneurysm Cardiovascular Events Diagnostic Test: Carotid Artery Reactivity test (CAR test) Diagnostic Test: Arterial stiffness

Detailed Description:

The investigators will include 167 patients under surveillance for AAA who are all currently under the threshold for repair (i.e. AAA diameter 40-50 mm for men and 35-45 mm for women). Participants will be recruited from all collaborating hospitals (Radboudumc, Rijnstate, CWZ) after providing written informed consent. Additionally, AAA-patients under surveillance of general practitioners are eligible (and will be contacted through the hospital-links), since the nature of the tests allow for performing all tests at the general practitioners' office.

In this observational, prospective study, a total of 167 patients under surveillance for an AAA, who are currently under threshold for repair (i.e. AAA diameter 40-50 mm for men and 35-44 mm for women), will be included. Baseline patient characteristics will be registered, including traditional risk factors and CV-history. In addition to regular care of measuring AAA diameter progression (in mm/year), the investigators will perform the CAR-test (10-min) and non-invasive arterial stiffness measures (PWA and PWV with the SphygmoCor device (10-min) one time as baseline. Furthermore, the investigators will ask patients to complete a questionnaire about the quality of their life (Appendix 1). A second questionnaire tries to clarify the disease experience of the patients and can be found in Appendix 2. Both questionnaires will be asked to be completed at the start and the end of the study. Subsequently, the investigators will record major adverse cardiovascular events (MACE) according to the International Classification of Disease-10. Registration of MACE will be performed using hospital-records and following international guidelines. Across a 2-year follow-up, by means of regular follow-up appointments, the investigators will examine AAA progression (in mm/year) and the ability of the CAR parameter and arterial stiffness parameters to predict CV-events.

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 167 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Tonometry (1) and Duplex Ultrasound (2) to Predict Abdominal Aorta Aneurysm (3) Progression and Cardiovascular Events in Aneurysm Patients
Actual Study Start Date : July 1, 2019
Estimated Primary Completion Date : April 1, 2021
Estimated Study Completion Date : January 2023
Arms and Interventions
Outcome Measures
Primary Outcome Measures :
  1. Major Adverse Cardiovascular Events (MACE) [ Time Frame: 2 year follow-up ]
    Incidence of MACE including myocardial infarction, cerebral infarction, heart failure, and peripheral vascular disease


Secondary Outcome Measures :
  1. SMART risk score [ Time Frame: Baseline ]
    Second Manifestations of ARTerial disease risk score is developed to determine the risk of recurrent vascular events based on clinical characteristics of the patients

  2. SphygmoCor parameters [ Time Frame: Baseline ]
    Peripheral pressure measurements (PWA)

  3. SphygmoCor parameters [ Time Frame: Baseline ]
    central pressure measurements (derived using a transfer function, PWA)

  4. SphygmoCor parameters [ Time Frame: Baseline ]
    abdominal pressure measurements (derived using a transfer function, PWA)

  5. SphygmoCor parameters - cardiac output parameter [ Time Frame: Baseline ]
    SEVR

  6. SphygmoCor parameters - cardiac output parameter [ Time Frame: Baseline ]
    ED

  7. SphygmoCor parameters [ Time Frame: Baseline ]
    PWV

  8. CAR-test results [ Time Frame: Baseline ]
    Percentage of vasodilation/vasoconstriction to the CAR test at the common carotid artery at baseline

  9. CAR-test results [ Time Frame: Baseline ]
    magnitude of the blood flow and perfusion response

  10. CAR-test results [ Time Frame: Baseline ]
    timing of the blood flow and perfusion response

  11. CAR-test results [ Time Frame: Baseline ]
    blood pressure responses

  12. CAR-test results [ Time Frame: Baseline ]
    heart rate responses

  13. AAA progression [ Time Frame: 2 year follow up ]
    AAA diameter progression in mm/year

  14. Aorta repair [ Time Frame: Within 2 year follow-up ]
    If the patient underwent aorta repair

  15. AAA rupture [ Time Frame: Within 2 year follow up ]
    If the AAA ruptured

  16. Score EQ-5D questionnaire [ Time Frame: At baseline and after 2 years ]
    Patient reported outcomes measured by the general health questionnaire

  17. Score IPQ-K questionnaire [ Time Frame: At baseline and after 2 years ]
    Patient reported outcomes measured by the disease perception questionnaire

  18. Clinical success [ Time Frame: 2 year follow up ]
    Incidence of serious adverse events


Other Outcome Measures:
  1. Demographic characteristics [ Time Frame: 2 year follow up ]
    Age

  2. Demographic characteristics [ Time Frame: 2 year follow up ]
    gender

  3. Demographic characteristics [ Time Frame: 2 year follow up ]
    height

  4. Demographic characteristics [ Time Frame: 2 year follow up ]
    weight

  5. Demographic characteristics [ Time Frame: 2 year follow up ]
    ASA class

  6. Demographic characteristics [ Time Frame: 2 year follow up ]
    medical history

  7. Demographic characteristics [ Time Frame: 2 year follow up ]
    blood pressure

  8. Demographic characteristics [ Time Frame: 2 year follow up ]
    heart rate

  9. Demographic characteristics [ Time Frame: 2 year follow up ]
    cardiac measurements

  10. Demographic characteristics [ Time Frame: 2 year follow up ]
    SVS class

  11. Medication use [ Time Frame: 2 year follow up ]
    Anti-platelets

  12. Medication use [ Time Frame: 2 year follow up ]
    anti-coagulants

  13. Medication use [ Time Frame: 2 year follow up ]
    anti-hypertensives

  14. Medication use [ Time Frame: 2 year follow up ]
    statins

  15. Medication use [ Time Frame: 2 year follow up ]
    beta-blockers

  16. Medication use [ Time Frame: 2 year follow up ]
    sympathicomimetics

  17. Laboratory results [ Time Frame: 2 year follow up ]
    Hemoglobin

  18. Laboratory results [ Time Frame: 2 year follow up ]
    serum creatinine

  19. Laboratory results [ Time Frame: 2 year follow up ]
    cholesterol

  20. Laboratory results [ Time Frame: 2 year follow up ]
    eGFR

  21. Laboratory results [ Time Frame: 2 year follow up ]
    crp

  22. Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    AAA sac diameter

  23. Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    infrarenal aortic neck lumen diameter

  24. Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    proximal non-aneurysmal aortic neck length

  25. Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    proximal aortic neck angle

  26. Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    aneurysm blood lumen diameter

  27. Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    common iliac artery diameter left

  28. Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    common iliac artery diameter right

  29. Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    blood lumen diameter


Eligibility Criteria
Contacts and Locations
Tracking Information
First Submitted Date May 29, 2019
First Posted Date June 18, 2019
Last Update Posted Date March 11, 2021
Actual Study Start Date July 1, 2019
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 14, 2019)
Major Adverse Cardiovascular Events (MACE) [ Time Frame: 2 year follow-up ]
Incidence of MACE including myocardial infarction, cerebral infarction, heart failure, and peripheral vascular disease
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: June 14, 2019)
  • SMART risk score [ Time Frame: Baseline ]
    Second Manifestations of ARTerial disease risk score is developed to determine the risk of recurrent vascular events based on clinical characteristics of the patients
  • SphygmoCor parameters [ Time Frame: Baseline ]
    Peripheral pressure measurements (PWA)
  • SphygmoCor parameters [ Time Frame: Baseline ]
    central pressure measurements (derived using a transfer function, PWA)
  • SphygmoCor parameters [ Time Frame: Baseline ]
    abdominal pressure measurements (derived using a transfer function, PWA)
  • SphygmoCor parameters - cardiac output parameter [ Time Frame: Baseline ]
    SEVR
  • SphygmoCor parameters - cardiac output parameter [ Time Frame: Baseline ]
    ED
  • SphygmoCor parameters [ Time Frame: Baseline ]
    PWV
  • CAR-test results [ Time Frame: Baseline ]
    Percentage of vasodilation/vasoconstriction to the CAR test at the common carotid artery at baseline
  • CAR-test results [ Time Frame: Baseline ]
    magnitude of the blood flow and perfusion response
  • CAR-test results [ Time Frame: Baseline ]
    timing of the blood flow and perfusion response
  • CAR-test results [ Time Frame: Baseline ]
    blood pressure responses
  • CAR-test results [ Time Frame: Baseline ]
    heart rate responses
  • AAA progression [ Time Frame: 2 year follow up ]
    AAA diameter progression in mm/year
  • Aorta repair [ Time Frame: Within 2 year follow-up ]
    If the patient underwent aorta repair
  • AAA rupture [ Time Frame: Within 2 year follow up ]
    If the AAA ruptured
  • Score EQ-5D questionnaire [ Time Frame: At baseline and after 2 years ]
    Patient reported outcomes measured by the general health questionnaire
  • Score IPQ-K questionnaire [ Time Frame: At baseline and after 2 years ]
    Patient reported outcomes measured by the disease perception questionnaire
  • Clinical success [ Time Frame: 2 year follow up ]
    Incidence of serious adverse events
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 14, 2019)
  • Demographic characteristics [ Time Frame: 2 year follow up ]
    Age
  • Demographic characteristics [ Time Frame: 2 year follow up ]
    gender
  • Demographic characteristics [ Time Frame: 2 year follow up ]
    height
  • Demographic characteristics [ Time Frame: 2 year follow up ]
    weight
  • Demographic characteristics [ Time Frame: 2 year follow up ]
    ASA class
  • Demographic characteristics [ Time Frame: 2 year follow up ]
    medical history
  • Demographic characteristics [ Time Frame: 2 year follow up ]
    blood pressure
  • Demographic characteristics [ Time Frame: 2 year follow up ]
    heart rate
  • Demographic characteristics [ Time Frame: 2 year follow up ]
    cardiac measurements
  • Demographic characteristics [ Time Frame: 2 year follow up ]
    SVS class
  • Medication use [ Time Frame: 2 year follow up ]
    Anti-platelets
  • Medication use [ Time Frame: 2 year follow up ]
    anti-coagulants
  • Medication use [ Time Frame: 2 year follow up ]
    anti-hypertensives
  • Medication use [ Time Frame: 2 year follow up ]
    statins
  • Medication use [ Time Frame: 2 year follow up ]
    beta-blockers
  • Medication use [ Time Frame: 2 year follow up ]
    sympathicomimetics
  • Laboratory results [ Time Frame: 2 year follow up ]
    Hemoglobin
  • Laboratory results [ Time Frame: 2 year follow up ]
    serum creatinine
  • Laboratory results [ Time Frame: 2 year follow up ]
    cholesterol
  • Laboratory results [ Time Frame: 2 year follow up ]
    eGFR
  • Laboratory results [ Time Frame: 2 year follow up ]
    crp
  • Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    AAA sac diameter
  • Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    infrarenal aortic neck lumen diameter
  • Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    proximal non-aneurysmal aortic neck length
  • Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    proximal aortic neck angle
  • Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    aneurysm blood lumen diameter
  • Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    common iliac artery diameter left
  • Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    common iliac artery diameter right
  • Anatomic characteristics of AAA [ Time Frame: 2 year follow up ]
    blood lumen diameter
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Tonometry and Duplex Ultrasound to Predict AAA Progression and CV Events in Aneurysm Patients (1-2-3 Trial)
Official Title Tonometry (1) and Duplex Ultrasound (2) to Predict Abdominal Aorta Aneurysm (3) Progression and Cardiovascular Events in Aneurysm Patients
Brief Summary

Abdominal aortic aneurysm (AAA) is a common vascular disease and associated with risk of rupture, but also with a high cardiovascular (CV) event rate. A key difficulty in AAA is predicting these life-threatening complications, highlighting the need to explore the potential of novel techniques. Both progression of AAA and CV events are strongly linked to vascular health. In 2013, the SMART risk score is developed to calculate the risk of the patients for recurrent vascular events based on clinical characteristics. Recently, a novel, easy to perform, non-invasive test of endothelial function (the carotid artery reactivity (CAR) test), reflecting target organ damage, has recently been introduced. The CAR is a simple, quick (5-min), non-invasive test that uses ultrasound to examine the carotid artery in response to sympathetic stimulation by placing one hand in cold water. This test shows strong agreement with both coronary and aortic responses to sympathetic stimulation and predicted CV events in patients with peripheral arterial disease.

The aim of this prospective 2-year follow-up study is to investigate the predictive capacity of the CAR-test in comparison to the SMART risk score for the development of cardiovascular events in patients with an abdominal aortic aneurysm who have not yet reached the treatment threshold. This could aid clinical decision making in the need for (surgical) intervention, but also alter (drug) treatment to reduce risk of cardiovascular events. Secondary objectives are to investigate the predictive capacity of the CAR-test for progression of the abdominal aortic aneurysm, and to evaluate QoL scores in patients under surveillance for AAA. The aim is to provide insight if these scores can help clinical decision making.

Detailed Description

The investigators will include 167 patients under surveillance for AAA who are all currently under the threshold for repair (i.e. AAA diameter 40-50 mm for men and 35-45 mm for women). Participants will be recruited from all collaborating hospitals (Radboudumc, Rijnstate, CWZ) after providing written informed consent. Additionally, AAA-patients under surveillance of general practitioners are eligible (and will be contacted through the hospital-links), since the nature of the tests allow for performing all tests at the general practitioners' office.

In this observational, prospective study, a total of 167 patients under surveillance for an AAA, who are currently under threshold for repair (i.e. AAA diameter 40-50 mm for men and 35-44 mm for women), will be included. Baseline patient characteristics will be registered, including traditional risk factors and CV-history. In addition to regular care of measuring AAA diameter progression (in mm/year), the investigators will perform the CAR-test (10-min) and non-invasive arterial stiffness measures (PWA and PWV with the SphygmoCor device (10-min) one time as baseline. Furthermore, the investigators will ask patients to complete a questionnaire about the quality of their life (Appendix 1). A second questionnaire tries to clarify the disease experience of the patients and can be found in Appendix 2. Both questionnaires will be asked to be completed at the start and the end of the study. Subsequently, the investigators will record major adverse cardiovascular events (MACE) according to the International Classification of Disease-10. Registration of MACE will be performed using hospital-records and following international guidelines. Across a 2-year follow-up, by means of regular follow-up appointments, the investigators will examine AAA progression (in mm/year) and the ability of the CAR parameter and arterial stiffness parameters to predict CV-events.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients under surveillance for an AAA, who are currently under threshold for repair (i.e. AAA diameter 40-50 mm men and 35-44 mm for women), will be included. AAA patients will be recruited from all collaborating hospitals (Radboudumc, Rijnstate, CWZ), who provide written informed consent. Additionally, also AAA-patients under surveillance of general practitioners are eligible (and will be contacted through the hospital-links), since the nature of the tests allow for performing all tests at the general practitioners' office.
Condition
  • Abdominal Aortic Aneurysm
  • Cardiovascular Events
Intervention
  • Diagnostic Test: Carotid Artery Reactivity test (CAR test)
    The CAR test will be applied to stimulate the sympathetic nervous system. This thermal stimulus is known to elevate blood pressure via sympathetic pathways, so it can be used to study the vascular response to sympathetic activation. The participant will submerge their left hand in a bucket of ice water (approximately 4 degrees celcius) for 3 minutes, which is reported to be sufficient to induce a maximal dilation in the common carotid artery. At baseline and every minute after the hand is submerged in ice water, the blood pressure will be measured to check whether a sympathetic stimulation is achieved.
  • Diagnostic Test: Arterial stiffness

    The SphygmoCor device will be used to non-invasively measure arterial stiffness parameters using applanation tonometry. For Pulse Wave Analyses (PWA), the radial waveform will be recorded. Approximately 10 waveforms are averaged, resulting in several non-invasive parameters:

    • Peripheral pressure parameters
    • Central and abdominal aneurysm pressure parameters (derived using a transfer function)
    • Cardiac output parameters (SEVR, ED)

    Pulse wave velocity will be performed by recording the waveforms of the carotid and femoral artery sequentially. The travelled distance will be measured according to the current guidelines and entered in the program. The program will calculate the PWV based on 10 ECG triggered waveform of each artery.

Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 14, 2019)
167
Original Estimated Enrollment Same as current
Estimated Study Completion Date January 2023
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Male or female at least 18 years old;
  • Informed consent form understood and signed and patient agrees to follow- up visits;
  • Has an abdominal aortic aneurysm (AAA), who is still under surveillance;

Exclusion Criteria:

  • Life expectancy < 2 years;
  • Psychiatric or other condition that may interfere with the study;
  • Participating in another clinical study, interfering on outcomes;
  • Increased risk for coronary spasms (score Rose-questionnaire ≥2; this questionnaire can be found in Appendix 3);
  • Presence of Raynaud's phenomenon, chronic pain syndrome at upper extremity(s), presence of an AV fistula or shunt, open wounds to the upper extremity(s), and/or scleroderma associated with placing the hand in ice water;
  • Recent (<3 months) presence of angina pectoris, myocardial infarction, cerebral infarction, and/or heart failure, or PAD treatment.
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts
Contact: Michel Reijnen, MD, prof 0880057282 MReijnen@rijnstate.nl
Contact: Jenske Vermeulen, MSc. 0880057282 JVermeulen@rijnstate.nl
Listed Location Countries Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number NCT03989011
Other Study ID Numbers NL68953.091.19
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Rijnstate Hospital
Study Sponsor Rijnstate Hospital
Collaborators
  • Radboud University
  • Canisius-Wilhelmina Hospital
Investigators
Principal Investigator: Michel Rijnen, MD, prof Rijnstate Hospital
PRS Account Rijnstate Hospital
Verification Date March 2021