Hemodynamic Instability Prevented With Polaramine® Infusion Before Extracorporeal Circulation (HIPPIE)

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.

Study Overview

• Status: Completed
• Conditions: Hemodynamic Instability; Vasoplegic Syndrome
• Intervention / Treatment: Drug: dexchlorpheniramine (Polaramine®) injection; Drug: Placebo injection

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Pessac, France, 33604
    • CHU de Bordeaux

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; 24 patients	Drug: dexchlorpheniramine (Polaramine®) injection; 5 minutes before CPB, patients will receive 10 mg (2 ml) of Polaramine®
Placebo Comparator: Control group; 24 patients	Drug: Placebo injection; 5 minutes before CPB, patients will receive 2 ml of normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assesment of patients proportion with abnormal ratio of sympathic-parasympathetic balance (>1.2)	The calculation of every ratio will be made by a software in the department	Day 0
Assesment of patients proportion with abnormal ratio of sympathic-parasympathetic balance (>1.2)	The calculation of every ratio will be made by a software in the department	Day 1
Assesment of patients proportion with abnormal ratio of sympathic-parasympathetic balance (>1.2)	The calculation of every ratio will be made by a software in the department	Day 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood dosage of histamine	Day 0
Immunophenotypage of basophilic polynuclears	Day 0
Peaks of pressure measure in the lung artery perioperative	Day 0, day 1, day 2
Assesment of the postoperative complications incidence	Day 28, month 6
Measure of the amount of fluids delivered	Day 0, day1, day 2
Measure of the amount of catecholamine infused	Day 0, day 1, day 2
Duration of hospital stay	Day 28
Mortality	Day 28, month 6
Collection of adverse events potentially related to the treatment	Day 0, day1, day 2, day 28, month 6
Assesment of patients proportion presenting metabolic disease, with abnormal ratio of sympathic-parasympathetic balance (>1.2)	Day 0, day 1, day 2

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Study Chair: Antoine BENARD, Dr, University Hospital, Bordeaux; Principal Investigator: Cédrick ZAOUTER, Dr, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2016
• Primary Completion (Actual): July 18, 2017
• Study Completion (Actual): July 18, 2017

Study Registration Dates

• First Submitted: January 11, 2016
• First Submitted That Met QC Criteria: February 2, 2016
• First Posted (Estimate): February 5, 2016

Study Record Updates

• Last Update Posted (Actual): May 13, 2020
• Last Update Submitted That Met QC Criteria: May 12, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: cardiopulmonary bypass; norepinephrine; Cardiac surgery; dexchlorpheniramine; H1 blockers; histamine release
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Vasoplegia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Dexchlorpheniramine
• Other Study ID Numbers: CHUBX 2014/13

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No