Variations in the Hemostatic System Induced by a Standardized Walking Test

NCT ID: NCT06418633

Last Updated: 2025-02-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

94 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-11

Study Completion Date

2027-04-01

Brief Summary

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Two groups of patients will be compared: One group of patients with a history of venous thromboembolic disease and one group without. Both groups will be subjected to a walking test and with electrocardiogram measurements and blood tests.

Detailed Description

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Induced venous thromboembolism is a situation in which venous thromboembolic disease is triggered by an acute event that activates hemostasis: surgery, trauma, infectious or inflammatory outbreak, etc., a situation in which the risk of spontaneous recurrence, in the absence of a new provoking circumstance, is low, leading to the suggestion, not of long-term thromboprophylaxis, but simply the transient prevention of an event when there is a new clinical event likely to activate hemostasis. One such event is acute physical exertion.

Indeed, cohort studies seem to show that regular physical activity is associated with a low incidence of venous thromboembolism. Trained individuals have an endogenous thrombotic potential, assessed by the thrombin TGT test, lower than that of sedentary controls. A 3-month regimen of daily endurance exercise reduces thrombin generation controls and optimizes the fibrinolytic system. Repetitive exercise is accompanied by a depletion of exercise-induced platelet activation. However, several cases of venous thromboembolism have been reported in high-level athletes without usual risk factors and acute high-intensity rowing induces an acute increase in thrombin generation immediately after exercise, which disappears within 16 to 24 hours. The relationship between the level of physical activity and the risk of VTE could be a U-shaped relation, with an increasing risk of event in intense acute practice.

However, no data exists on the hemostatic impact of an acute session of physical activity in patients with a history of venous thromboembolism. Thus, the hypothesis is that exercise-induced response of hemostasis differ in patients with an history of provoked VTE compared to subjects without a history of venous thromboembolism.

This is a proof-of-concept, pathophysiological, single-center, cross-sectional, prospective comparison study of a group of patients with a personal history of induced Venous thromboembolism to a group of sex- and age- and sex-matched controls (+/- 5 years).

\- Type of clinical study: Stress test-induced variations in parameters describing the results of the thrombin generation test (Thromboscreen®) in a group of Patients (Cases) will be compared with those obtained in a group of Control subjects (Controls) with a ratio 1:1.

The Patients group comprises 47 patients with a personal history of induced venous thromboembolism, the last event dating back to more than 6 months, whose clinical phenotype did not justify long-term antithrombotic drug prophylaxis.The Control group comprises 47 patients with no personal history of venous thromboembolism and no family history of venous thromboembolism in first-degree relatives.

The study intervention consists of an hour-long walking test and two blood tests in both groups for all participants (Controls and Patients).

\- Intra-individual reproducibility will be analyzed in 20 subjects (10 patients and 10 controls) who will take the walking test twice on two separate days.

Patients will be selected during a venous thromboembolism follow-up consultation by a physician from either department (Vascular Medicine Consultation or Biological Hematology and Consultations).Inclusion and non-inclusion criteria will be checked, and the study will be explained to participants (patients and controls).Patients and controls will be systematically asked to take part in the variability analysis on a voluntary basis, until 10 subjects per group have agreed to carry out the second test.

The walking test is performed in the morning, 2 hours after a standard breakfast, on a treadmill. It will be preceded by a clinical examination, a resting 12-lead electrocardiogram and a brachial pressure measurement. After a 3-minute warm-up and "habituation" period (walking speed 2.5 km per hour with no incline), the speed and incline will be gradually increased until a target heart rate close to the theoretical ventilatory threshold, and of the order of 70% of the theoretical maximum value (evaluated by Astrand's formula: 220-age), so as to maintain aerobic exercise conditions of moderate intensity, enabling prolonged effort to be maintained. Blood samples will be taken from each participant whilst at rest, before undergoing the 60-minute walking test, in a sitting position, and just after the exercise test.

Conditions

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Venous Thromboembolism

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

This is a single-center, prospective, cross-sectional, proof-of-concept study,
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Control group

Subjects with neither a personal history nor family history of venous thromboembolism in first-degree relatives.

Group Type ACTIVE_COMPARATOR

60-minute walking test

Intervention Type OTHER

Treadmill walking test in the morning, 2 hours after breakfast, following a clinical examination, resting 12-lead electrocardiogram and blood pressure measurement. After a 3-minute warm-up and walking of speed 2.5 km per hour, no incline, the speed and incline are gradually increased to reach a target heart rate close to the theoretical ventilatory threshold, around 70% of the theoretical maximum value (evaluated by Astrand's formula: 220-age), i.e. aerobic conditions of moderate intensity so that prolonged effort can be maintained. Test performed in presence of a physician trained in stress testing. Emergency cart and defibrillator available in the department. Intra-hospital vital emergency protocol in place, with resuscitation teams on standby. The cardiology department, in the same building, can be contacted in the event of a cardiological abnormality during the test or recovery. The test takes 60 minutes, including a 3-minute initial warm-up.

Static blood test

Intervention Type DIAGNOSTIC_TEST

33.3 ml of blood will be taken from each participant whilst at rest, before undergoing the 60-minute walking test

Post-effort blood test

Intervention Type DIAGNOSTIC_TEST

33.3 ml of blood will be taken from each participant immediately after undergoing the 60-minute walking test.

Electrocardiogram

Intervention Type OTHER

An electrocardiogram will be carried out throughout the exercise period and during the first 30 minutes of recovery.

Blood pressure monitoring

Intervention Type OTHER

Blood pressure will be monitored out throughout the exercise period and during the first 30 minutes of recovery.

Patients

Patients with a personal history of induced venous thromboembolism, the last attack dating back to more than 6 months, whose clinical phenotype did not justify long-term antithrombotic drug prophylaxis

Group Type ACTIVE_COMPARATOR

60-minute walking test

Intervention Type OTHER

Treadmill walking test in the morning, 2 hours after breakfast, following a clinical examination, resting 12-lead electrocardiogram and blood pressure measurement. After a 3-minute warm-up and walking of speed 2.5 km per hour, no incline, the speed and incline are gradually increased to reach a target heart rate close to the theoretical ventilatory threshold, around 70% of the theoretical maximum value (evaluated by Astrand's formula: 220-age), i.e. aerobic conditions of moderate intensity so that prolonged effort can be maintained. Test performed in presence of a physician trained in stress testing. Emergency cart and defibrillator available in the department. Intra-hospital vital emergency protocol in place, with resuscitation teams on standby. The cardiology department, in the same building, can be contacted in the event of a cardiological abnormality during the test or recovery. The test takes 60 minutes, including a 3-minute initial warm-up.

Static blood test

Intervention Type DIAGNOSTIC_TEST

33.3 ml of blood will be taken from each participant whilst at rest, before undergoing the 60-minute walking test

Post-effort blood test

Intervention Type DIAGNOSTIC_TEST

33.3 ml of blood will be taken from each participant immediately after undergoing the 60-minute walking test.

Electrocardiogram

Intervention Type OTHER

An electrocardiogram will be carried out throughout the exercise period and during the first 30 minutes of recovery.

Blood pressure monitoring

Intervention Type OTHER

Blood pressure will be monitored out throughout the exercise period and during the first 30 minutes of recovery.

Individual reproducibility" subgroup: controls

10 subjects with neither a personal history nor family history of venous thromboembolism in first-degree relatives who have accepted to re-do the test one week later.

Group Type ACTIVE_COMPARATOR

60-minute walking test

Intervention Type OTHER

Treadmill walking test in the morning, 2 hours after breakfast, following a clinical examination, resting 12-lead electrocardiogram and blood pressure measurement. After a 3-minute warm-up and walking of speed 2.5 km per hour, no incline, the speed and incline are gradually increased to reach a target heart rate close to the theoretical ventilatory threshold, around 70% of the theoretical maximum value (evaluated by Astrand's formula: 220-age), i.e. aerobic conditions of moderate intensity so that prolonged effort can be maintained. Test performed in presence of a physician trained in stress testing. Emergency cart and defibrillator available in the department. Intra-hospital vital emergency protocol in place, with resuscitation teams on standby. The cardiology department, in the same building, can be contacted in the event of a cardiological abnormality during the test or recovery. The test takes 60 minutes, including a 3-minute initial warm-up.

Static blood test

Intervention Type DIAGNOSTIC_TEST

33.3 ml of blood will be taken from each participant whilst at rest, before undergoing the 60-minute walking test

Post-effort blood test

Intervention Type DIAGNOSTIC_TEST

33.3 ml of blood will be taken from each participant immediately after undergoing the 60-minute walking test.

Electrocardiogram

Intervention Type OTHER

An electrocardiogram will be carried out throughout the exercise period and during the first 30 minutes of recovery.

Blood pressure monitoring

Intervention Type OTHER

Blood pressure will be monitored out throughout the exercise period and during the first 30 minutes of recovery.

Individual reproducibility" subgroup: patients

10 patients with a history of induced venous thromboembolism, the last attack dating back to more than 6 months, whose clinical phenotype did not justify long-term antithrombotic drug prophylaxis, who have accepted to re-do the test one week later.

Group Type ACTIVE_COMPARATOR

60-minute walking test

Intervention Type OTHER

Treadmill walking test in the morning, 2 hours after breakfast, following a clinical examination, resting 12-lead electrocardiogram and blood pressure measurement. After a 3-minute warm-up and walking of speed 2.5 km per hour, no incline, the speed and incline are gradually increased to reach a target heart rate close to the theoretical ventilatory threshold, around 70% of the theoretical maximum value (evaluated by Astrand's formula: 220-age), i.e. aerobic conditions of moderate intensity so that prolonged effort can be maintained. Test performed in presence of a physician trained in stress testing. Emergency cart and defibrillator available in the department. Intra-hospital vital emergency protocol in place, with resuscitation teams on standby. The cardiology department, in the same building, can be contacted in the event of a cardiological abnormality during the test or recovery. The test takes 60 minutes, including a 3-minute initial warm-up.

Static blood test

Intervention Type DIAGNOSTIC_TEST

33.3 ml of blood will be taken from each participant whilst at rest, before undergoing the 60-minute walking test

Post-effort blood test

Intervention Type DIAGNOSTIC_TEST

33.3 ml of blood will be taken from each participant immediately after undergoing the 60-minute walking test.

Electrocardiogram

Intervention Type OTHER

An electrocardiogram will be carried out throughout the exercise period and during the first 30 minutes of recovery.

Blood pressure monitoring

Intervention Type OTHER

Blood pressure will be monitored out throughout the exercise period and during the first 30 minutes of recovery.

Interventions

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60-minute walking test

Treadmill walking test in the morning, 2 hours after breakfast, following a clinical examination, resting 12-lead electrocardiogram and blood pressure measurement. After a 3-minute warm-up and walking of speed 2.5 km per hour, no incline, the speed and incline are gradually increased to reach a target heart rate close to the theoretical ventilatory threshold, around 70% of the theoretical maximum value (evaluated by Astrand's formula: 220-age), i.e. aerobic conditions of moderate intensity so that prolonged effort can be maintained. Test performed in presence of a physician trained in stress testing. Emergency cart and defibrillator available in the department. Intra-hospital vital emergency protocol in place, with resuscitation teams on standby. The cardiology department, in the same building, can be contacted in the event of a cardiological abnormality during the test or recovery. The test takes 60 minutes, including a 3-minute initial warm-up.

Intervention Type OTHER

Static blood test

33.3 ml of blood will be taken from each participant whilst at rest, before undergoing the 60-minute walking test

Intervention Type DIAGNOSTIC_TEST

Post-effort blood test

33.3 ml of blood will be taken from each participant immediately after undergoing the 60-minute walking test.

Intervention Type DIAGNOSTIC_TEST

Electrocardiogram

An electrocardiogram will be carried out throughout the exercise period and during the first 30 minutes of recovery.

Intervention Type OTHER

Blood pressure monitoring

Blood pressure will be monitored out throughout the exercise period and during the first 30 minutes of recovery.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Patients who have given written informed consent.
* Patients who are affiliated to or beneficiaries of a social security scheme.


* Patients with a personal history of provoked venous thromboembolism, venous thrombosis and/or pulmonary embolism, with the last attack dating back to more than 6 months, and whose clinical phenotype did not justify long-term antithrombotic drug prophylaxis.

Definition of provoked venous thromboembolism : The clinical criteria used to classify venous thromboembolism as provoked are :

* First year of combined oestrogen-progestogen oral contraception, or contraception using an oestrogen-impregnated vaginal ring or transcutaneous synthetic oestrogen patch.
* Hormonal stimulation for oocyte retrieval
* Pregnancy and 6 weeks post-partum
* Surgery
* Trauma
* Immobilisation in plaster or splint
* Outbreak of acute infectious disease
* Acute flare-up of inflammatory disease
* Prolonged air travel lasting at least 4 hours
* Prolonged strict bed rest lasting at least 3 consecutive days.


* Subjects with no personal history of venous thromboembolism
* Subjects with no family history of venous thromboembolism in first-degree relatives
* Subjects of the same sex and age with a tolerance of +/- 5 years in relation to the matched case.

Exclusion Criteria

* Patients who are physically unable to perform the 60-minute walking test, for any reason, in particular cardiovascular contraindications to exercise (recent acute coronary syndrome unstable angina, rhythm disorders, tight aortic stenosis, cardiac heart failure, acute myocarditis, pericarditis or endocarditis endocarditis, poorly controlled hypertension, pre-stress blood pressure \> 200/110 mmHg, recent stroke or transient ischemic attack).
* Patients on anticoagulant or antithrombotic treatment, ongoing or discontinued within the last month.
* Patients treated for pulmonary embolism who remain dyspneic after anticoagulant treatment and requiring a work-up for pulmonary hypertension.
* Last surgery dating back to less than 3 months.
* Known chronic morbidities: diabetes mellitus, chronic inflammatory or infectious disease, heart failure, renal insufficiency, hepatic insufficiency or arterial thrombosis dating back to less than 3 months.
* For women: treatment containing synthetic or natural estrogen, in progress or discontinued for less than a month
* Pregnancy within the last year.
* Difficult venous access.
* Regular practice of an intensive sporting/physical activity, such as running, tennis, cycling etc. of more than 3 hours per week.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Antonia PEREZ MARTIN, Prof.

Role: PRINCIPAL_INVESTIGATOR

Nîmes University Hospital

Stéphane FAURE

Role: PRINCIPAL_INVESTIGATOR

Nîmes University Hospital

Locations

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CHU de Nîmes

Nîmes, Occitanie, France

Site Status RECRUITING

Countries

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France

Central Contacts

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Antonia PEREZ MARTIN, Prof.

Role: CONTACT

+334 66 68 33 13

Anissa MEGZARI

Role: CONTACT

+33466684236

Facility Contacts

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Antonia PEREZ MARTIN, Pr.

Role: primary

+33 4 66 68 33 13

References

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Gris JC, Guillotin F, Dos Santos TP, Chea M, Loubet P, Laureillard D, Sotto A, Muller L, Barbar SD, Roger C, Lefrant JY, Jung B, Klouche K, Mura T, Quere I, Perez-Martin A. Prognostic value of an automated thrombin generation assay in COVID-19 patients entering hospital: A multicentric, prospective observational study. Thromb Res. 2023 Feb;222:85-95. doi: 10.1016/j.thromres.2022.12.019. Epub 2023 Jan 2.

Reference Type BACKGROUND
PMID: 36608393 (View on PubMed)

Other Identifiers

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NIMAO 2023 1

Identifier Type: -

Identifier Source: org_study_id

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