An interventional study of Full dose DPT with propofol and Full dose DPT with ketamine in Allergic Reaction, Hypersensitivity and Perioperative Complication, sponsored by University Hospital, Antwerp. Completed at 1 site in Belgium. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-09-08.
Sponsored by University Hospital, Antwerp · Not applicable, Interventional, and Diagnostic
The goal of this clinical trial is to evaluate the safety and outcome of systematic drug provocation testing with anaesthetics at therapeutic doses in adult patients undergoing diagnostic work-up for perioperative hypersensitivity.
Perioperative hypersensitivity reactions (POH) pose a risk for major morbidity and mortality in the perioperative period. After resolution of the initial reaction it is crucial to determine the culprit drug to allow safe anaesthetics for future procedures.However this is not easy, as many drugs are administered near simultaneously and both anaesthesia and surgery may provoke or mask many of the symptoms of a hypersensitivity reaction. Conventional testing seems to offer good predictive value based on the low incidence of POH in subsequent re-exposures after negative work-up. Despite negative work-up anaesthetists often chose not to re-administer an neuromuscular blocking agent (NMBA) used in the index reaction, especially if no other culprit was found. This introduces an important bias as this group (no culprit found, NMBA not re-exposed) might be at the highest risk of containing false negatives as NMBA are the most frequent cause of POH in our region.The same remark can be made regarding earlier attempts by our group and others at establishing the negative predictive value (NPV) of conventional testing through retrospective analysis of subsequent re-exposures.To truly establish the NPV for conventional testing and thus the need for DPT, a prospective approach is needed where all patients are challenged with index drugs after negative conventional testing.
Adult patients that are referred for diagnostic work-up for POH will be included if they have a clinical history fitting with POH.
All patients will first receive a full diagnostic work-up for all index products consisting of in vivo (skin tests) and in vitro (specific IgE and -for drugs in which it is available- basophil activation tests). Clinical reactions (both index reactions and any reactions during DPT) will be classified according to the National Audit Program (NAP-6) classification which separates non-fatal POH in 4 grades:
Skin tests will be performed at the allergology day clinic following the protocols of the French Society for Anaesthesia and Intensive Care and the French Society of Allergology. Based on these results we make a distinction between patients with an identified culprit and those without an identified culprit.
If a culprit has been found, all other index drugs are challenged at therapeutic doses. The standard testing is performed for alternatives for the culprit drug in the same drug class (such as NMBA) and one drug from this class that tests negative is also used in a challenge at a therapeutic dose.
If no culprit has been found after the initial work-up of skin tests and in vitro tests the next step is determined by the severity of the initial reaction. In NAP-6 grade 1-3 reactions all index drugs are challenged at therapeutic doses. As the benefits of DPT have yet to be fully quantified the risk-benefit analysis in the most severe reactions (NAP 4) is difficult to make. Hence, we use an 'confirmation by elimination' principle in these cases in which we only challenge with the drugs that do not carry the highest likelihood of being the culprit. This likelihood is based on both timing and epidemiology as NMBA are a much more common cause of POH in our region than all other anaesthetics combined. By eliminating all other drugs we 'clear' them for future use and gain confidence in our suspicion of the most likely culprit without having to administer them in this population.
100 studies on the registry are indexed under Anaphylaxis; 20 are open to participants now.
This study's enrollment of 50 is above the median of 40 across 50 interventional studies indexed under Anaphylaxis.
Browse Anaphylaxis studies →University Hospital, Antwerp is the lead sponsor of 242 studies on the registry; 66 are open to participants now.
Compared within Anaphylaxis, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Hypersensitivity. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
incremental administration of investigated anesthetics up to full therapeutic dose in POH patients.
Diagnostic Test: Full dose DPT with propofol · Diagnostic Test: Full dose DPT with ketamine · Diagnostic Test: Full dose DPT with etomidate · Diagnostic Test: Full dose DPT with midazolam · Diagnostic Test: Full dose DPT with fentanyl · Diagnostic Test: Full dose DPT with sufentanyl · Diagnostic Test: Full dose DPT with alfentanil · Diagnostic Test: Full dose DPT with remifentanil · Diagnostic Test: Full dose DPT with rocuronium · Diagnostic Test: Full dose DPT with atracurium · Diagnostic Test: Full dose DPT with cisatracurium · Diagnostic Test: Full dose DPT with succinylcholine
Incremental administration of propofol up to a cummulative full therapeutic dose (2mg/kg) in POH patients investigated for propofol. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.02mg/kg-0.2 mg/kg -0.6 mg/kg -1.2mg/kg).
Incremental administration of ketamine up to a cummulative full therapeutic dose (1mg/kg) in POH patients investigated for ketamine. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.01 mg/kg -0.1 mg/kg -0.3 mg/kg -0.6mg/kg).
Incremental administration of etomidate up to a cummulative full therapeutic dose (0.2mg/kg) in POH patients investigated for etomidate. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.002 mg/kg -0.02 mg/kg -0.06 mg/kg -1.2mg/kg).
Incremental administration of midazolam up to a cummulative full therapeutic dose (0.05mg/kg) in POH patients investigated for midazolam. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.0005 mg/kg -0.005 mg/kg -0.015 mg/kg -0.03mg/kg).
Incremental administration of fentanyl up to a cummulative full therapeutic dose (1mcg/kg) in POH patients investigated for fentanyl. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.01 mcg/kg -0.1 mcg/kg -0.3 mcg/kg -0.6mcg/kg).
Incremental administration of sufentanyl up to a cummulative full therapeutic dose (0.1mcg/kg) in POH patients investigated for sufentanyl. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.001 mcg/kg -0.01 mcg/kg -0.03 mcg/kg -0.06µg/kg).
Incremental administration of alfentanil up to a cummulative full therapeutic dose (10mcg/kg) in POH patients investigated for alfentanil. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.1 mcg/kg -1 mcg/kg -3 mcg/kg -6µg/kg).
Incremental administration of remifentanil up to a cummulative full therapeutic dose (0.5mcg/kg) in POH patients investigated for remifentanil. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose, 3/10th of the dose and ultimately 6/10th of the dose (0.005 mcg/kg -0.05 mcg/kg -0.15 mcg/kg -0.3µg/kg).
Incremental administration of rocuronium up to a cummulative full therapeutic dose (0.6mg/kg) in POH patients investigated for rocuronium. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose (0.006 mg/kg -0.06 mg/kg ). In a second session 3/10th of the dose and ultimately 7/10th of the dose (0.18 mg/kg -0.42mg/kg) are administerd under general anesthesia.
Incremental administration of atracurium up to a cummulative full therapeutic dose (0.5mg/kg) in POH patients investigated for atracurium. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose (0.005 mg/kg -0.05 mg/kg ). In a second session 3/10th of the dose and ultimately 7/10th of the dose (0.15 mg/kg -0.35mg/kg) are administered under general anesthesia .
Incremental administration of cisatracurium up to a cummulative full therapeutic dose (0.15mg/kg) in POH patients investigated for cisatracurium. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose (0.0015 mg/kg -0.015 mg/kg ). In a second session 3/10th of the dose and ultimately 7/10th of the dose (0.045 mg/kg -0.105mg/kg) are administered under general anesthesia .
Incremental administration of succinylcholine up to a cummulative full therapeutic dose (1mg/kg) in POH patients investigated for succinylcholine. Doses will be administered every 15 minutes starting at 1/100th of the dose, followed by 1/10th of the dose (0.01 mg/kg -0.1 mg/kg). In a second session 3/10th of the dose and ultimately 7/10th of the dose (0.3 mg/kg -0.7mg/kg) are administered under general anesthesia.
Hypersensitivity during DPT
Prevalence of hypersensitivity during direct provocation for drugs that tested negatively in conventional tests.
Time frame: 1 hour
Severe reactions during DPT
Prevalence of severe (NAP 3-4) hypersensitivity reactions during direct provocation testing
Time frame: 1 hour
Adverse events during DPT
Prevalence of adverse events during or after direct provocation testing
Time frame: 1 hour
Sensitivity of conventional tests
Sensitivity of skin tests, specific IgE and basophil activation tests for anaesthetics
Time frame: 1 hour
Ran from Oct 2023 to primary completion in Jun 2025, 20 months.
Of 13 interventional studies with no phase under Anaphylaxis, half reached primary completion within 12 months of starting (the median), counting those still running; a quarter within 6 and three quarters within 37. This study's 20 months is above that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.
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