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Vancomycin Associated Red Man Syndrome (RMS)

This study has been completed.
Sponsor:
Collaborator:
Katherine Berry Richardson Foundation
Information provided by (Responsible Party):
Angela Myers, Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier:
NCT00824122
First received: January 14, 2009
Last updated: October 11, 2011
Last verified: October 2011
  Purpose

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.


Condition Phase
Red Man Syndrome
Phase 4

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Genetic Polymorphisms Associated With Histamine Disposition in Children With Vancomycin Associated Red Man Syndrome (RMS)

Resource links provided by NLM:


Further study details as provided by Children's Mercy Hospital Kansas City:

Primary Outcome Measures:
  • Presence or abscence of genetic polymorphisms in the histamine pathway in patients with vancomycin related RMS. [ Time Frame: During Hospital Admission ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Frozen blood has been maintained for future genetic studies


Enrollment: 544
Study Start Date: January 2008
Study Completion Date: October 2011
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Children greater than 6 months receiving at least one dose of Vancomycin and Red Man Syndrome
2
Children greater than 6 months receiving at least one dose of Vancomycin and has not had Red Man Syndrome

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.

  Eligibility

Ages Eligible for Study:   6 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00824122

Locations
United States, Missouri
Children's Mercy Hospital & Clinics
Kansas City, Missouri, United States, 64108
Sponsors and Collaborators
Children's Mercy Hospital Kansas City
Katherine Berry Richardson Foundation
Investigators
Principal Investigator: Angela Myers, MD, MPH Children's Mercy Hosptials and Clinics
  More Information

No publications provided by Children's Mercy Hospital Kansas City

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Angela Myers, Assistant Professor of Pediatrics, Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier: NCT00824122     History of Changes
Other Study ID Numbers: 10914
Study First Received: January 14, 2009
Last Updated: October 11, 2011
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Multiple Endocrine Neoplasia
Syndrome
Disease
Endocrine Gland Neoplasms
Endocrine System Diseases
Genetic Diseases, Inborn
Neoplasms
Neoplasms by Site
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Pathologic Processes
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014