Vancomycin Associated Red Man Syndrome (RMS)

NCT ID: NCT00824122

Last Updated: 2011-10-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 544 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2011-10-31

Brief Summary

This study proposes to identify patients who developed RMS with vancomycin infusion, and determine presence or absence of variant alleles involved in histamine biotransformation. The implications of this study are important, as identification of variant alleles in these patients, may alter the current standard of care for vancomycin infusions.

The hypothesis of this study is that the development of red man syndrome (RMS) during receipt of intravenous vancomycin is associated with the presence of variant alleles for genes involved in the histamine pathway. The primary outcome that will be measured will be the history of RMS and the presence or absence of variant alleles for the genes responsible for histamine metabolism (i.e. histamine n-methyltransferase and diamine oxidase). As a secondary endpoint, the study will also attempt to determine the incidence of RMS in pediatric patients.

Detailed Description

Vancomycin has been utilized as an antimicrobial therapeutic agent for serious gram positive infections for more than half a century.The pharmacokinetics of vancomycin has been well studied, and in general there are few side effects from this medication. The most common side effect that occurs with receipt of vancomycin is red man syndrome (RMS), which is also known as red neck, or red person syndrome.1 RMS encompasses a spectrum that ranges from a mild reaction such as flushing, urticarial rash, pruritis, to a severe reaction that includes generalized erythema,intense pruritis, and even hypotension. RMS has been estimated to occur in 5- 50% of hospitalized patients who receive this drug.

RMS is considered an anaphylactoid type of reaction that is due to mast cell degranulation with a concomitant rise in blood histamine levels. The resultant symptomatology varies from mild itching and erythematous rash to a more generalized reaction with hypotension. This reaction has been shown to be modified by pre-treatment with various types of antihistamines including diphenhydramine and cimetidine.

There is now evidence to suggest that altered histamine metabolism contributes to the pathogenesis of various disorders. Histamine is almost exclusively metabolized by the enzymes histamine N-methyltranserase (HNMT)and diamine oxidase (DAO) both of which are polymorphically expressed in people with varying frequencies.HNMT catalyzes the N- methylation of histamine. This is the predominant pathway for histamine metabolism,accounting for 50-80% of its biotransformation. Diamine oxidase (DAO) likely contributes in a significant manner of the remaining metabolism of histamine as only 2-3% of this autocoid is excreted unchanged in the urine. It is plausible that allelic variants of HNMT and/or DAO may contribute to histmaminergic reactions in a given patient with resultant propagation of its pharmacologic effects, and that polymorphically expressed enzymes primarily responsible for terminating the pharmacologic activity of histamine (via biotransformation)may play a crucial role in determining disease phenotype for disorders (e.g., RMS) where histamine is a key mediator.

This is a prospective study that will be conducted over a one year period of time. Eligible patients will be identified by a search of patients who are receiving vancomycin therapy throughout the study period. Chart review/patient interview will then be performed to identify patients who developed symptomatology consistent with RMS while receiving vancomycin infusion. For the purposes of this study, red man syndrome (RMS) will be defined as: erythematous rash, flushing of the face, neck, or torso, itching, or a lowering of systolic or diastolic blood pressure by >10mm/hg. A subset of patients who remained asymptomatic throughout their vancomycin therapy will also be evaluated as a control group.

Conditions

Red Man Syndrome

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

1

Children greater than 6 months receiving at least one dose of Vancomycin and Red Man Syndrome

No interventions assigned to this group

2

Children greater than 6 months receiving at least one dose of Vancomycin and has not had Red Man Syndrome

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Patients must have received vancomycin

Exclusion Criteria

• Patients who have received antihistamines at the time of vancomycin administration or
• Patients who have been on steroids or tricyclic antidepressants within 30 days prior to the vancomycin administration
• People receiving ECMO or have multiorgan failure
• Currently receiving dialysis

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Katherine Berry Richardson Foundation

UNKNOWN

Sponsor Role: collaborator

Children's Mercy Hospital Kansas City

OTHER

Sponsor Role: lead

Responsible Party

Angela Myers

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Angela Myers, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Children's Mercy Hosptials and Clinics

Locations

Children's Mercy Hospital & Clinics

Kansas City, Missouri, United States

Countries

United States

References

Myers AL, Gaedigk A, Dai H, James LP, Jones BL, Neville KA. Defining risk factors for red man syndrome in children and adults. Pediatr Infect Dis J. 2012 May;31(5):464-8. doi: 10.1097/INF.0b013e31824e10d7.

Reference Type: DERIVED

PMID: 22327873 (View on PubMed)

Other Identifiers

10914

Identifier Type: -

Identifier Source: org_study_id