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Drug Challenges Without Prior Skin Testing

Phase 1
Completed
Conditions
Antibiotic Allergy
Drug Hypersensitivity
Penicillin Allergy
Interventions
Drug: Placebo-Controlled Graded Drug Challenge
Registration Number
NCT03158831
Lead Sponsor
Montefiore Medical Center
Brief Summary

The investigators are conducting a prospective study to determine the safety and outcomes of placebo-controlled graded drug challenges without prior skin testing in patients with a low-risk history of antibiotic hypersensitivity reaction based on history alone. The investigators hypothesize that the rate of reaction to graded drug challenges without prior skin testing in patients with a low-risk history of drug hypersensitivity reaction based on history alone will not be meaningfully more than the rate of reaction to placebo. The investigators hypothesize that the rate of adverse reactions to drug challenges without prior skin testing will not be meaningfully more than the rate of adverse reactions with prior skin testing as was observed in the investigators' historical clinic cohort.

Detailed Description

Graded drug challenges are the gold standard to exclude an immediate hypersensitivity reaction in patients with a low likelihood of drug allergy and are considered standard of care. Patients who tolerate a graded challenge are deemed to not be allergic to the drug and are not at increased risk for future reactions compared with the general population. Prior studies of graded challenges in appropriately selected patients have demonstrated low reaction rates with symptoms that were mainly mild and subjective in nature. The investigators are conducting a prospective study to determine the safety and outcomes of placebo-controlled graded drug challenges without prior skin testing in patients with a low-risk history of antibiotic hypersensitivity reaction based on history alone. Skin testing requires a separate visit and is, therefore, more time-consuming and costly than performing a graded challenge without skin testing. The investigators believe that they can determine if patients are at low-risk to react to an antibiotic based on a detailed history and, therefore, do not require skin testing prior to a challenge. Given the majority of symptoms to graded drug challenges reported in prior studies were mild and subjective, the investigators hypothesize that the rate of reaction to graded drug challenges without prior skin testing in patients with a low-risk history of drug hypersensitivity reaction based on history alone will not be meaningfully more than the rate of reaction to placebo. The investigators hypothesize that the rate of adverse reactions to drug challenges without prior skin testing will be not meaningfully more than the rate of adverse reactions with prior skin testing as was observed in the investigators' historical clinic cohort. All patients age 7 years or older with a history of a non-life-threatening reaction to an antibiotic are eligible to participate in a placebo-controlled graded drug challenge. The challenge is comprised of placebo followed by 30 minutes of observation, 1/10th of the treatment dose of the antibiotic the patient reported a reaction followed by 30 minutes of observation, and the full dose of the antibiotic followed by 1 hour of observation. All patients will be contacted via telephone within one month of a negative challenge to determine whether they experienced a delayed reaction. All patients will also be contacted via telephone within one year of a negative challenge to determine if they have safely taken the challenge drug.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
166
Inclusion Criteria
  • All patients seven years of age or older who have a low-risk, non-life-threatening history of adverse reaction to an antibiotic.
Exclusion Criteria
  • Patients under the age of seven.
  • Pregnant patients.
  • Patients with a history of a drug reaction that is high-risk and life-threatening including life-threatening angioedema, bronchospasm, or anaphylactic shock or a history of severe non-IgE-mediated reactions including serum sickness, Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, hepatitis, hemolytic anemia, DRESS, skin and/or oral blisters, hypersensitivity vasculitis, pneumonitis, or pulmonary fibrosis.
  • Patients who have taken antihistamines within 3 days of the drug challenge.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Placebo-Controlled Graded Drug ChallengePlacebo-Controlled Graded Drug ChallengeThis is a single arm study. All patients will receive a placebo prior to a graded drug challenge. Each patient serves as his/her own control.
Primary Outcome Measures
NameTimeMethod
Rate of unexpected reaction to graded drug challenges without prior skin testing compared to rate of unexpected reaction to graded drug challenges with prior skin testing.It is anticipated the study will take 2 years to enroll 200 patients with subsequent data comparison.

Determine the rate of unexpected reaction to a graded drug challenge without prior skin testing versus the rate of reaction to a graded drug challenge with prior skin testing in the investigators' historical cohort (data on this cohort has already been published: Iammatteo M, Ferastraoaru D, Koransky R, Alvarez-Arango S, Thota N, Akenroye A, Jerschow E. Identifying Allergic Drug Reactions Through Placebo-Controlled Graded Challenges. J Allergy Clin Immunol Pract. 2017 May - Jun;5(3):711-717.e2.).

Secondary Outcome Measures
NameTimeMethod
Rate of unexpected reaction to graded drug challenges versus placebosPatients are monitored for 1 hour after completion of their drug challenge.

Determine the rate of unexpected reaction to graded drug challenges without prior skin tests versus the rate of unexpected reaction to placebos in patients with a low-risk history of drug hypersensitivity reaction based on history alone.

Rate of unexpected delayed reaction to graded drug challengesPatients are called within 1 month of their challenge to determine if they had any delayed reactions.

Determine the rate of unexpected delayed reaction to graded challenges

Trial Locations

Locations (1)

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

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