Understanding "Heparin Resistance" in Cardiac Surgery

NCT01598883 | Completed Phase 1

• 1 other identifier: Altered Heparin Responsiveness
• Study Type: interventional
• Target: 504
• Locations: 1 country
• Sites: 1

Brief Summary

This study will explore altered heparin responsiveness (AHR) in cardiac surgical patients undergoing cardiopulmonary bypass (CPB) requiring systemic anticoagulation with heparin. The investigators will evaluate the hypothesis that AHR may be directly related to, modulated or mediated by interactions between heparin, antithrombin (AT), the heparin-AT complex, and one or more acute phase proteins. The investigators are particularly interested in identifying patients with "true heparin resistance", that is, patients who demonstrate AHR even after antithrombin-replenishment in the presence of an adequate systemic dose of heparin.

Conditions

Cardiopulmonary Bypass; Altered Heparin Response

Outcome Measures

Primary Outcomes (1)

• Altered Heparin Responsivness (AHR)

  We will first identify patients with AHR as defined by an ACT \<450 seconds (the MGH standard target ACT after the initial dose of heparin for CPB). We will evaluate the hypothesis that AHR may be directly related to, modulated or mediated by interactions between heparin, antithrombin (AT), the heparin-AT complex, and one or more acute phase proteins.

  Participants will be followed from the administration of the initial heparin bolus to being placed on CPB, an average of 15 minutes.

Secondary Outcomes (1)

• "True Heparin Resistance"

  Patients will be followed from the administration of the initial heparin bolus to being placed on CPB, an average of 15 minutes.

Study Arms (2)

ACT after initial heparin bolus less than 450

OTHER

If a patients activated clotting time (ACT) is less than 450 after the bolus dose of heparin (350U/kg) they will be randomized to one of two interventions.

Drug: Heparin; Drug: ATryn

ACT after first intervention less than 450

ACTIVE COMPARATOR

Drug: Heparin; Drug: ATryn

Interventions

Heparin DRUG

150 U/kg

Also known as: Heparin Sodium

ACT after first intervention less than 450; ACT after initial heparin bolus less than 450

ATryn DRUG

1000 IU

Also known as: Antithrombin (recombinant)

ACT after first intervention less than 450; ACT after initial heparin bolus less than 450

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients scheduled for elective cardiac or aortic surgery requiring CPB for which heparin will be used for systemic anticoagulation
• Patients scheduled for urgent surgery who are hemodynamically stable and capable of giving voluntary consent
• Patients with platelet factor 4 antibody positivity (antiPF4+) for whom heparin anticoagulation will be used

You may not qualify if:

• Patients for whom heparin will not be used for anticoagulation
• Patients with known congenital AT-deficiency
• Patients with known goat milk allergy

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• rEVO Biologics: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Interventions

Heparin; Antithrombins

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anticoagulants; Hematologic Agents; Therapeutic Uses

Study Officials

• Greg Koski, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Greg Koski, PhD, MD, CPI (Honorary)

Study Record Dates

• First Submitted: April 24, 2012
• First Posted: May 15, 2012
• Study Start: June 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 14, 2016

Record last verified: 2016-12

Locations

US (1)