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

NCT07034066 | Completed DMC

• 1 other identifier: Sant Joan de Deu Foundation
• Study Type: observational
• Target: 257
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

NSAID; Biomarkers; Phenotyping; Children

Keywords

NSAID-hipersensitivity in children; children drug allergy

Outcome Measures

Primary Outcomes (1)

• Clinical characteristics of pediatric patients with NSAID hypersensitivity, based on historical data and development of a diagnostic protocol.

  In both the retrospective and prospective arm, the investigators reviewed the medical records of patients who completed DPT. Participant demographic data were reviewed, including age, sex, personal and family history of atopy, and the results of DPTs performed on suspected medications and alternatives if necessary. Final phenotypes after DPT were: * Cross-intolerance (CI) * Selective hypersensitivity (SH)

  Retrospective arm: review of the medical records took about 4-6 months Prospective arm: from enrollment to DPT, 6-8 months.

Secondary Outcomes (3)

• Differences in clinical features across different pediatric age groups.

  Retrospective arm: review of the medical records took about 4-6 months Prospective arm: from enrollment to DPT, 6-8 months.

• Rate of tolerance to alternative NSAIDs among patients with confirmed hypersensitivity.

  Retrospective arm: review of the medical records took about 4-6 months Prospective arm: from enrollment to DPT, 6-8 months.

• Diagnostic performance of in vivo and in vitro tests.

  Prospective arm: from enrollment to DPT, 6-8 months.

Study Arms (2)

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.

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

Eligibility Criteria

• Age: 1 Month - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

The study population consists of pediatric patients (aged 0 to 17 years) with a clinical suspicion or confirmed diagnosis of hypersensitivity NSAID. Retrospective Cohort: Includes all patients who underwent at least one drug provocation test (DPT) for suspected NSAID hypersensitivity between January 2014 and December 2021 at the Pediatric Allergy Department of Hospital Sant Joan de Déu. Prospective Cohort: Includes newly referred patients to the outpatient Pediatric Allergy Clinic from August 2022 to December 2024, presenting with clinical symptoms suggestive of NSAID hypersensitivity. Eligibility is determined based on: * Clinical manifestations (cutaneous and/or respiratory) following NSAID intake. * A high likelihood of an adverse drug reaction based on history. * Informed consent signed by parents or legal guardians. * Patients with incomplete DPTs or those whose guardians decline consent (for the prospective arm) are excluded.

You may qualify if:

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

You may not qualify if:

• Patients who did not undergo or complete the DPT

Sponsors & Collaborators

• Fundació Sant Joan de Déu: lead
• Hospital Sant Joan de Deu: collaborator

Study Sites (1)

Hospital Sant Joan de Deu

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Related Publications (5)

• 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.

  PMID: 33474858 RESULT

• 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.

  PMID: 39365158 RESULT

• 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.

  PMID: 28986120 RESULT

• 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.

  PMID: 36199560 RESULT

• 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.

  PMID: 29693290 RESULT

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 11 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2025
• First Posted: June 24, 2025
• Study Start: March 15, 2022
• Primary Completion: December 30, 2024
• Study Completion: May 1, 2025
• Last Updated: June 24, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Data will be available beginning 6 months after publication and will remain accessible for 5 years.
• Access Criteria: Data will be shared with qualified researchers affiliated with academic or healthcare institutions, for purposes of academic research or meta-analysis, and can be used for further analysis of the intervention's efficacy, safety profiling, or inclusion in systematic reviews. Study protocol, statistical analysis plan, and informed consent forms (in anonymized format) will also be made available. Requests should be submitted to the corresponding author by email. A data access agreement must be signed, and the research proposal will be reviewed by the study steering committee before approval is granted.

Locations

ES (1)