Chronic Remote Ischemic Preconditioning as a Complement to Conventional Prenatal Care for Preeclampsia

Study Overview
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Brief Summary
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Pre-eclampsia is a disease specific to pregnancy that affects 3-5% of women. It is defined by the appearance of high blood pressure after 20 weeks of amenorrhea associated with the presence of proteins in the urine, dysfunction of organs such as the liver, kidneys, lungs or brain, or dysfunction of the placenta. The cause of this disease is still unclear but it would most likely be a placental origin. Pre-eclampsia is a progressive disease that can lead to important complications. To date, there is no treatment for pre-eclampsia other than childbirth and more particularly placental delivery. Nevertheless, it is possible in some cases to stabilize arterial hypertension and thus to hope for a prolongation of the pregnancy. Our research project aims to study the effect of preconditioning on blood pressure. Preconditioning consists of using a blood pressure cuff and inflating it on the upper limb -like during a standard blood pressure measurement- for several minutes followed by a rest period in order to create ischemia-reperfusion periods. This technique would allow the release of beneficial substances into the bloodstream that would lower blood pressure. This method has been used for several years in different specialties and has produced good results on the heart, kidneys, lungs and brain. With this technique we hope to stabilize or even reduce blood pressure in cases of pre-eclampsia and thus prolong the pregnancy.

Official Title
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Chronic Remote Ischemic Preconditioning as a Complement to Conventional Prenatal Care for Preeclampsia: a One-center Prospective Randomized Study for Women With Non-severe Preeclampsia Between 24 and 37 Weeks' Gestation

Conditions
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Preeclampsia

Intervention / Treatment
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* Other: Preconditionning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Singleton pregnancy Gestational age between 24 0/7 and 36 6/7 weeks' gestation Hospitalization for non-severe pre-eclampsia (non-severe hypertension = Systolic blood pressure between 140 and 160mmHg, diastolic blood pressure between 90 and 110mmHg associated with one of these: proteinuria >=300mg/24h/thrombocytopenia 100-150G/L/central symptoms such as headache responding to standard analgesics/hyperreflexia without clonus/decreased fibrinogen/haptoglobin <0.1/utero-placental dysfunction with IUGR and/or umbilical Doppler Class II) Maternal age >18 years Good comprehension of French allowing easy understanding of the information protocol and the consent form Exclusion Criteria: Chronic hypertension Renal disease Pre-pregnancy diabetes Autoimmune disease (SAPL, SLE, Sjögren) Severe PE (Systolic blood pressure >160mmHg, diastolic blood pressure >140mmHg, hepatic cytolysis at twice the norm, right hypochondrium or epigastric pain, central symptoms such as clonus or headache resistant to usual treatment or disturbed consciousness, thrombocytopenia <100G/L, acute pulmonary edema, renal failure defined by doubling of baseline creatinine value or creatinine >97 micromol/L) Suspected fetal anomaly or malformation HELLP syndrome Eclampsia attack Pathological fetal monitoring Known maternal upper limb vascular anomaly Severe maternal cardiac pathology Maternal history of deep vein thrombosis of the upper limb

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preconditionning<br>Ischemia will be obtained after inflating the cuff to a pressure of 200 mmHg (or a pressure at least 50 mmHg above the patient's systolic pressure). After a five-minute period, the cuff will be deflated and the arm allowed to reperfuse for five minutes. These maneuvers will be repeated until 3 cycles of ischemia- reperfusion have been completed once a day. Patients will experiment with this procedure for at least 5 days. | Other: Preconditionning<br>* Remote ischemic conditioning will be induced using a Tourniquet cuff applied to the patient's non-dominant arm. The device used will be an Ulrich Kariba machine. A strip of absorbent cotton will be applied to the arm and the tension cuff will be placed over it in a standard way. The systolic pressure and the application time will be set manually. Ischemia will be obtained after inflating the cuff to a pressure of 200 mmHg (or a pressure at least 50 mmHg above the patient's systolic pressure). After a five-minute period, the cuff will be deflated and the arm allowed to reperfuse for five minutes. These maneuvers will be repeated until 3 cycles of ischemia- reperfusion have been completed once a day. Patients will experiment with this procedure for at least 5 days.<br>|
| No Intervention: Control<br>For subjects assigned to the control group, the pneumatic cuff is placed around the upper arm, and inflation of a blood pressure to a lower pressure (50mmHg) which will result in no impairment of antegrade flow. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease blood pressure | Comparison of mean of decrease in systolic and diastolic blood pressure (intervention vs placebo) between day 1 and day 5 using ANOVA test | Up to 13 weeks | 
| Decreased blood pressure patients | Comparison of the number of patients who significantly decreased blood pressures (≥6%), Chi-squared test or Fisher exact test if appropriate | Up to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SFLT/PLGF change | Comparison of mean change in the SFLT/PLGF ratio | Up to 13 weeks | 
| Uterine artery resistance index change | Comparison of mean change in the uterine artery resistance index (using ANOVA test) | Up to 13 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preconditioning