Pediatric Non-Steroidal Anti-Inflammatory Drugs (NSAID) Allergy Study

NCT ID: NCT07034066

Last Updated: 2025-06-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

257 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-03-15

Study Completion Date

2025-05-01

Brief Summary

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Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most commonly used medications to treat pain and inflammation. Many are available over the counter and are frequently used in children to reduce fever and relieve pain. Hypersensitivity (HS) to NSAIDs affects an estimated 0.6% to 5.7% of the general population. These reactions can be caused by immune or non-immune mechanisms. In most cases, they fall into two categories: reactions to a single NSAID or to several different NSAIDs.

Currently, the main way to diagnose NSAID hypersensitivity is through a drug provocation test (DPT)-this involves giving the patient the suspected drug under medical supervision to check for a reaction. It's considered the most reliable method. However, diagnosing these reactions in children can be challenging. Symptoms can vary widely, and there are few accurate alternative tests available to replace the DPT.

This study looks for easier ways-like symptoms or lab tests-to diagnose NSAID reactions, so fewer patients need to go through multiple DPT.

Detailed Description

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Hypersensitivity reactions (HSR) to NSAID in children, although similar to those in adults, present unique challenges in terms of diagnosis and management. While international classification systems are useful, real-world clinical scenarios often fall outside established criteria. Examples include:

* Multiple NSAID HSR involving both cutaneous and respiratory symptoms.
* NSAID-induced anaphylaxis dependent on food intake.
* Immediate selective reactions to more than one NSAID. These scenarios are frequently observed in pediatric patients, highlighting the need for a regional study to evaluate and properly address them.

This is a single-center, ambispective observational study.

Primary Objective:

To describe the clinical characteristics of children with NSAID hypersensitivity.

Secondary Objectives:

1. To describe the different clinical phenotypes and assess age-related differences.
2. To assess tolerance to alternative NSAIDs in patients with confirmed hypersensitivity.
3. To evaluate the usefulness of in vivo and in vitro tests in the diagnostic process.
4. To disseminate study findings.

The study design is based on 2 components:

* Retrospective Component: include participants diagnosed with NSAID HSR, who underwent DPT in the Pediatric Allergy Department at Hospital Sant Joan de Déu between January 2014 and December 2021. Data will be pseudonymized. A waiver of informed consent will be requested due to the long study period, the absence of risk, and the fact that many patients are no longer under follow-up.
* Prospective Component: participants with suspected NSAID HSR were included. Participants will be assessed during outpatient visits, where the following steps will occur:
* In vivo testing, where appropriate, using validated prick and intradermal techniques for paracetamol and metamizole. Controls will include saline (negative) and histamine (positive).
* A DPT will be performed with the suspected medication and/or suitable alternatives, in accordance with standard clinical practice.
* Nasal DPT using a rhinomanometer for patients suspected of NSAID-exacerbated respiratory disease (NERD).
* Families will be informed about the procedures, and informed consent will be obtained.

On the day of the DPT, a blood test (including total IgE, IgG, IgA, IgM, tryptase, IL-6) and urine sample (uLTE4 levels) will be collected.

If the DPT is positive, a second round of blood and urine samples will be collected.

The NSAID to be used in testing are commonly prescribed in pediatric practice and grouped by chemical structure:

Salicylic acid derivatives: Aspirin Para-aminophenol derivatives: Paracetamol (acetaminophen) Propionic acid derivatives: Ibuprofen, naproxen Acetic acid derivatives: Diclofenac Enolic acid derivatives: Pyrazolones, oxicams Fenamates (fenamic acid derivatives) COX-2 inhibitors: Celecoxib

Conditions

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NSAID Biomarkers Phenotyping Children

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

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Prospective Cohort

Includes new patients referred to the Pediatric Allergy outpatient clinic with suspected NSAID hypersensitivity.

Inclusion Criteria:

Children aged 0-17 years Clinical suspicion of NSAID hypersensitivity

Exclusion Criteria:

Refusal to provide informed consent

At the first outpatient visit:

A complete medical history and physical exam will be performed The need for DPT (oral/nasal) will be explained to the family Informed consent will be obtained On admission for oral DPT: blood and urine samples will be collected DPT will be conducted via oral route unless the original reaction occurred after intravenous administration Positive DPTs will be followed by sample collection and symptom management A follow-up phone call will be made within 6 months to assess home tolerance

For patients undergoing nasal DPT, the test will be conducted in the hospital's ENT unit, and follow-up will depend on the result.

No interventions assigned to this group

Retrospective Cohort

Includes all patients who underwent a DPT for NSAID hypersensitivity between 2014 and 2021 in the Pediatric Allergy Unit.

Inclusion Criteria:

Children aged 0-17 years Completed DPT with the suspected and/or alternative NSAID

Exclusion Criteria:

Patients who did not undergo or complete the DPT

Upon protocol approval, data on all hospital admissions related to NSAID hypersensitivity evaluation (2014-2021) will be requested. Clinical records will be reviewed after pseudonymization, which will be performed by an independent individual, Ms. Silvia del Valle, who will also safeguard the pseudonymization key. This complies with legal requirements for accessing medical records without consent, under CEIm approval, including:

Functional and technical separation between investigators and data processors Explicit confidentiality and non-reidentification commitment

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Children aged 0-17 years
* Completed DPT with the suspected and/or alternative NSAID

Exclusion Criteria

* Patients who did not undergo or complete the DPT
Minimum Eligible Age

1 Month

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Sant Joan de Deu

OTHER

Sponsor Role collaborator

Fundació Sant Joan de Déu

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospital Sant Joan de Deu

Esplugues de Llobregat, Barcelona, Spain

Site Status

Countries

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Spain

References

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Klaewsongkram J, Buranapraditkun S, Mongkolpathumrat P, Palapinyo S, Chantaphakul H. Clinical Characteristics, Urinary Leukotriene E4 Levels, and Aspirin Desensitization Results in Patients With NSAID-Induced Blended Reactions. Allergy Asthma Immunol Res. 2021 Mar;13(2):229-244. doi: 10.4168/aair.2021.13.2.229.

Reference Type RESULT
PMID: 33474858 (View on PubMed)

Dona I, Saenz de Santa Maria R, Moreno EM, Bartra J, Torres MJ. An algorithm for the diagnosis and treatment of nonsteroidal antiinflammatory drugs hypersensitivity, 2024 update. Allergy. 2025 Apr;80(4):1183-1186. doi: 10.1111/all.16349. Epub 2024 Oct 4. No abstract available.

Reference Type RESULT
PMID: 39365158 (View on PubMed)

Blanca-Lopez N, Haroun-Diaz E, Ruano FJ, Perez-Alzate D, Somoza ML, Vazquez de la Torre Gaspar M, Rivas-Ruiz F, Garcia-Martin E, Blanca M, Canto G. Acetyl Salicylic Acid Challenge in Children with Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs Differentiates Between Cross-Intolerant and Selective Responders. J Allergy Clin Immunol Pract. 2018 Jul-Aug;6(4):1226-1235. doi: 10.1016/j.jaip.2017.08.029. Epub 2017 Oct 3.

Reference Type RESULT
PMID: 28986120 (View on PubMed)

Cavkaytar O, Arga M. NSAID Hypersensitivity in the Pediatric Population: Classification and Diagnostic Strategies. J Asthma Allergy. 2022 Sep 28;15:1383-1399. doi: 10.2147/JAA.S267005. eCollection 2022.

Reference Type RESULT
PMID: 36199560 (View on PubMed)

Kidon M, Blanca-Lopez N, Gomes E, Terreehorst I, Tanno L, Ponvert C, Chin CW, Caubet JC, Soyer O, Mori F, Blanca M, Atanaskovic-Markovic M. EAACI/ENDA Position Paper: Diagnosis and management of hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) in children and adolescents. Pediatr Allergy Immunol. 2018 Aug;29(5):469-480. doi: 10.1111/pai.12915. Epub 2018 Jun 13.

Reference Type RESULT
PMID: 29693290 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: last version

View Document

Document Type: Study Protocol: first version

View Document

Other Identifiers

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Sant Joan de Deu Foundation

Identifier Type: -

Identifier Source: org_study_id

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