Drug Challenges Without Prior Skin Testing

NCT ID: NCT03158831

Last Updated: 2021-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-13
• Study Completion Date: 2021-10-01

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.

Conditions

Drug Hypersensitivity; Penicillin Allergy; Antibiotic Allergy

Keywords

Drug Allergy; Penicillin Allergy; Antibiotic Allergy; Graded Drug Challenge

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Placebo-Controlled Graded Drug Challenge

This 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.

Group Type: OTHER

Placebo-Controlled Graded Drug Challenge

Intervention Type: DRUG

All patients receive a placebo followed by 30 minutes of observation. Patients then receive 1/10 of the treatment dose of the challenge drug followed by 30 minutes of observation. If no reaction, they will then receive a full dose of their challenge drug followed by 1 hour of observation. If they do not experience any reactions, they are deemed not to be allergic. All patients are asked to monitor for delayed reactions after the challenge. Patients are also called within 1 month of the challenge to determine if any delayed reactions occurred. Patients are called again within 1 year of the challenge to determine if they have subsequently taken the challenge drug and experienced any reactions.

Interventions

Placebo-Controlled Graded Drug Challenge

All patients receive a placebo followed by 30 minutes of observation. Patients then receive 1/10 of the treatment dose of the challenge drug followed by 30 minutes of observation. If no reaction, they will then receive a full dose of their challenge drug followed by 1 hour of observation. If they do not experience any reactions, they are deemed not to be allergic. All patients are asked to monitor for delayed reactions after the challenge. Patients are also called within 1 month of the challenge to determine if any delayed reactions occurred. Patients are called again within 1 year of the challenge to determine if they have subsequently taken the challenge drug and experienced any reactions.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Montefiore Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Elina Jerschow

Associate Professor of Clinical Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elina Jerschow, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center/Albert Einstein College of Medicine

Locations

Montefiore Medical Center

The Bronx, New York, United States

Countries

United States

References

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. doi: 10.1016/j.jaip.2016.09.041. Epub 2016 Nov 23.

Reference Type: BACKGROUND

PMID: 27888028 (View on PubMed)

Iammatteo M, Blumenthal KG, Saff R, Long AA, Banerji A. Safety and outcomes of test doses for the evaluation of adverse drug reactions: a 5-year retrospective review. J Allergy Clin Immunol Pract. 2014 Nov-Dec;2(6):768-74. doi: 10.1016/j.jaip.2014.08.001. Epub 2014 Sep 10.

Reference Type: BACKGROUND

PMID: 25439369 (View on PubMed)

Macy E, Romano A, Khan D. Practical Management of Antibiotic Hypersensitivity in 2017. J Allergy Clin Immunol Pract. 2017 May-Jun;5(3):577-586. doi: 10.1016/j.jaip.2017.02.014. Epub 2017 Mar 29.

Reference Type: BACKGROUND

PMID: 28365277 (View on PubMed)

Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273. doi: 10.1016/j.anai.2010.08.002.

Reference Type: BACKGROUND

PMID: 20934625 (View on PubMed)

Other Identifiers

2015-5610

Identifier Type: -

Identifier Source: org_study_id