Clinical trial NCT02675374: Hemodynamic Instability Prevented With Polaramine® Infusion Before Extracorporeal Circulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemodynamic Instability
Vasoplegic Syndrome
Keywords: Cardiac surgery
cardiopulmonary bypass
dexchlorpheniramine
H1 blockers
norepinephrine
histamine release
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2016-02-05
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This single-institution randomized controlled trial prospective will enrolled 48 patients scheduled for an aortic valve replacement. The objective of the present investigation is to determine the role of Polaramine® on reducing hemodynamic instability after separation from cardiopulmonary bypass (CPB) during cardiac surgery. Our hypothesis is that Polaramine® play an important role reducing dysfunction of the autonomic nervous system and hemodynamic stability after separation from CPB.

Detailed description: Vasoplegic syndrome is recognized as a common complication after CPB. Its incidence ranges from 5% to 25% after cardiac surgery requiring CPB. Such syndrome is related to an inflammatory reaction, which is attributed to the CPB. This syndrome is typically characterized by a combination of different parameters with low specificity and sensitivity, such as low systemic vascular resistance leading to a hypotension imposing perfusion of vasopressors with high or normal cardiac outputs.

Investigators preliminary data suggest that vasoplegic syndrome might be related to heart manipulation during surgery. Tearing maneuvers performed on the heart chambers trigger peaks pressure stimulating, consequently, baroreceptors and finally resulting in arteriovenous vasodilation via neurogenic and endogenous pathways. According to investigators initial investigation, such reaction appears to be related to basophils degranulation and release of vasoactive substances.

The hypothesis of the present trial is that a reduction of basophils degranulation and release of vasoactive substances via an antihistaminic could lower the incidence of the vasoplegic syndrome. This study aims to determine the effect of an antihistamine (dexchlorpheniramine (Polaramine®)) administered intravenously before CPB, on the vasoplegic syndrome incidence after separation from CPB.

Eligibility criteria: Inclusion Criteria:

* Men aged 18 and older
* Post menopausal women
* Patients scheduled for an aortic valve replacement with a traditional sternotomy and CPB

Exclusion Criteria:

* Patients with a left ventricular ejection fraction lower than 40%
* Patients with pulmonary arterial hypertension higher than 50mm of Hg,
* Redo cardiac surgery,
* Atrioventricular and intraventricular conduction disturbances
* Epilepsy or convulsions
* Atopic disease
* Women of childbearing potential
* Patients at risk of glaucoma
* Patients with therapy interacting with dexchlorpheniramine (Polaramine®).
* Patients unable to provide a signed informed consent

Primary outcomes:
measure: Assesment of patients proportion with abnormal ratio of sympathic-parasympathetic balance (>1.2)
timeFrame: Day 0
measure: Assesment of patients proportion with abnormal ratio of sympathic-parasympathetic balance (>1.2)
timeFrame: Day 1
measure: Assesment of patients proportion with abnormal ratio of sympathic-parasympathetic balance (>1.2)
timeFrame: Day 2
Secondary outcomes:
measure: Blood dosage of histamine
timeFrame: Day 0
measure: Immunophenotypage of basophilic polynuclears
timeFrame: Day 0
measure: Peaks of pressure measure in the lung artery perioperative
timeFrame: Day 0, day 1, day 2
measure: Assesment of the postoperative complications incidence
timeFrame: Day 28, month 6
measure: Measure of the amount of fluids delivered
timeFrame: Day 0, day1, day 2
measure: Measure of the amount of catecholamine infused
timeFrame: Day 0, day 1, day 2
measure: Duration of hospital stay
timeFrame: Day 28
measure: Mortality
timeFrame: Day 28, month 6
measure: Collection of adverse events potentially related to the treatment
timeFrame: Day 0, day1, day 2, day 28, month 6
measure: Assesment of patients proportion presenting metabolic disease, with abnormal ratio of sympathic-parasympathetic balance (>1.2)
timeFrame: Day 0, day 1, day 2
Other outcomes:
Locations:
city: Pessac
country: France
facility: CHU de Bordeaux
Study officials:
affiliation: University Hospital, Bordeaux
name: Cédrick ZAOUTER, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bordeaux
name: Antoine BENARD, Dr
role: STUDY_CHAIR
References: