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

Fundació Sant Joan de Déu

Status: Completed

Conditions: NSAID; Phenotyping; Biomarkers; Children

Study type: Observational

Funder types: Other

Identifiers

NCT07034066

Sant Joan de Deu Foundation

Details and patient eligibility

About

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.

Full description

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

Enrollment: 257 patients

Sex: All

Ages: 1 month to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

257 participants in 2 patient groups

Prospective Cohort

Description:

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

Description:

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