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NCT Number: NCT03989011

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

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.

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Key information

Sex eligibility

All sexes

Study type

Observational

Primary location

Canisius Wilhelmina Ziekenhuis, Nijmegen, Gelderland, Netherlands

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Carotid Artery Reactivity test (CAR test)

Diagnostic 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 celsius) 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.

Arterial Stiffness

Diagnostic Test

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.

Primary outcomes

  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 outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Rijnstate Hospital

Other

Collaborators

  • Canisius-Wilhelmina Hospital
  • Radboud University Medical Center

Registry information

Official study title

Tonometry (1) and Duplex Ultrasound (2) to Predict Abdominal Aorta Aneurysm (3) Progression and Cardiovascular Events in Aneurysm Patients

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Jun 18, 2019
Registry last updated
Apr 11, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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