Effect of Anti-histamine in Prevention Systolic Hypotension After Protamine

• ClinicalTrials.gov Identifier: NCT03583567
• Recruitment Status: Completed
• First Posted: July 11, 2018
• Last Update Posted: September 1, 2021
• Sponsor: Mahidol University
• Information provided by (Responsible Party): Mahidol University

Study Description

Brief Summary:

Protamine remains the anticoagulant of choice for cardiopulmonary bypass (CPB). The process of protamine neutralization of heparin came with the side effects sometimes; it can be life threatening or fetal reaction. The adverse cardiopulmonary response of protamine has been observed during entire history of clinical cardiac surgery. The true mechanism reaction is difficult to defined and the complexity of the clinical situation The classification of protamine reaction has been divided in to main 3 types (transient systemic hypotension secondary to rapid administration, anaphylactic and anaphylactoid reaction and catastrophic pulmonary vasoconstriction.

The reaction from pharmacologic histamine release is the most common type of reaction. Protamine was believed to induce hypotension by this mechanism, and it was demonstrated to release histamine by degranulation of isolated mast cells From the hypothesis that the systemic hypotension cause by the released of histamine. The investigators will measure the serum tryptase which is the enzyme that released from degranulation of human mast cell. Comparing the serum tryptase level of the patient at baseline, 30 min and 60 min after protamine was given.

There for the hypothesis of this study is administrating of H1 and H2 blocker helps attenuate the drop in MAP after protamine is given.

Condition or disease	Intervention/treatment	Phase
Protamine Adverse Reaction	Drug: Chlorpheniramine and ranitidine; Drug: 0.9% Normal Saline	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: normal saline will be used as placebo in control group
• Primary Purpose: Prevention
• Official Title: A Randomized Controlled Study Comparing the Prophylactic Effect of histamine1 and Histamine 2 Receptor Blocker in Prevention Systolic Hypotension After Protamine Administration in Cardiac Patient Having Cardiopulmonary Bypass
• Actual Study Start Date: September 5, 2018
• Actual Primary Completion Date: March 31, 2019
• Actual Study Completion Date: March 31, 2019

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: 0.9% Normal Saline; Syringe No 1 contain normal saline 1 mL Syringe No 2 contain normal saline 2 mL	Drug: 0.9% Normal Saline; Patient will receive normal saline as placebo.
Experimental: Chlorpheniramine and ranitidine; Syringe No 1 contain chlorpheniramine 10 mg (1 mL) Syringe No 2 contain ranitidine 50 mg (2 mL)	Drug: Chlorpheniramine and ranitidine; Patient will receive intravenous chlorpheniramine and ranitidine prior to protamine.

Outcome Measures

Primary Outcome Measures :

1. Blood pressure [ Time Frame: 37 minutes ]
   Systolic and diastolic blood pressure will be recorded every minutes since the start of protamine infusion (in 7 minutes) til 30 minutes after infusion.

Secondary Outcome Measures :

1. Serum tryptase [ Time Frame: 60 minutes ]
   Serum tryptase will be measured before the administration of protamine and at 30 minutes and 60 minutes after protamine

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• ASA physical status 1-3
• Schedule for open heart surgery

Exclusion Criteria:

• History of allergy to the study drugs or protamine
• History of previous cardiac surgery or received protamine
• History of diabetes with insulin therapy

Contacts and Locations

Locations

Thailand

Siriraj Hospital

Bangkok, Thailand, 10700

Sponsors and Collaborators

Mahidol University

Investigators

• Principal Investigator: Sirilak Suksompong, MD; Mahidol University

More Information

• Responsible Party: Mahidol University
• ClinicalTrials.gov Identifier: NCT03583567
• Other Study ID Numbers: Si 2018
• First Posted: July 11, 2018
• Last Update Posted: September 1, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mahidol University:

protamine; antihistamine

Additional relevant MeSH terms:

Hypotension; Vascular Diseases; Cardiovascular Diseases; Chlorpheniramine; Ranitidine; Ranitidine bismuth citrate; Anti-Ulcer Agents; Gastrointestinal Agents; Histamine H2 Antagonists; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antipruritics; Dermatologic Agents; Histamine H1 Antagonists; Anti-Allergic Agents