Ignite Creation Date:
2024-05-11 @ 8:31 AM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06406114
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-10
First Post:
2024-04-17
Brief Title:
Optimizing the Diagnostic Approach to Cephalosporin Allergy Testing
Sponsor:
Massachusetts General Hospital
Organization:
Massachusetts General Hospital
Study Overview
Official Title:
Optimizing the Diagnostic Approach to Cephalosporin Allergy Testing
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DACAT
Brief Summary:
Cephalosporin antibiotics are commonly used but can result in allergic reactions and anaphylaxis There is no clear diagnostic approach for cephalosporin-allergic patients and guidance for the use of other antibiotics in allergic patients is based on side chain chemical similarity and limited skin testing evidence This project includes a clinical trial and mechanistic studies to optimize the approach to cephalosporin allergy and advance future diagnostics
Detailed Description:
Background
In the United States beta-lactam antibiotics are the leading cause of allergic reactions Cephalosporin antibiotics in particular are the most common cause of drug-induced anaphylaxis and perioperative allergy For penicillin allergy the mechanism of allergy and the antigenic determinants are known validated penicillin skin testing followed by drug challenge has a 100 negative predictive value to exclude an immunoglobulin IgE-mediated reaction For cephalosporin allergy the antigenic determinants and mechanism are not known and skin testing is not validated The diagnostic test characteristics of skin testing with native cephalosporins remain unclear with no sensitivity nor specificity reported Although beta-lactam cross-reactivity has been hypothesized to be from the similarity of the R1 side chains rather than the beta-lactam ring cross-reactivity estimates among beta-lactams vary Furthermore it is not known whether the variance in cross-reactivity is due to true allergy versus sensitization based on positive skin testing given that drug challenges were not performed on skin-test-positive patients While an IgE mechanism is assumed for cephalosporin allergy and supported by skin testing that has been positive the biology has yet to be characterized and some cephalosporin anaphylaxis can occur on the first exposure which is inconsistent with an IgE mechanism Given the complexity of cephalosporin structures and potential epitopes there may be several distinct biologic pathways involved in cephalosporin allergy Future diagnostics in cephalosporin allergy are reliant on determination of these biological pathways and finding key haptens
Aims
Current national practice guidelines related to cephalosporin allergy assessment are considered conditional and based on low-quality evidence The overall goal is to identify the optimal diagnostic approach to cephalosporin allergy and determine beta-lactam cross-reactivity while discovering the mechanism and antigenic determinants of cephalosporin allergy to advance future diagnostics The investigators will do this through a clinical trial that will generate empirical evidence through novel trial procedures double-blind skin testing and double-blind placebo-controlled drug challenges Specific aims are 1 To determine the optimal approach to cephalosporin allergy evaluation 2 To assess beta-lactam cross-reactivity in cephalosporin-allergic individuals and 3 To investigate the antigenic determinants and mechanism of cephalosporin allergy
Study Overview
Enrolled and consented subjects will attend visit 1 for baseline screening sample collection double-blind skin testing to a beta-lactam panel and a double-blind placebo-controlled challenge to their culprit cephalosporin antibiotic Results of the culprit cephalosporin challenge determine subjects study timeline Subjects confirmed as non-allergic to their culprit cephalosporin will return for visit 2 for venipuncture and blood collection ending their participation in the study Subjects who are confirmed as allergic to their culprit at visit 1 will return for three additional visits visits 2 and 3 will include double-blind placebo-controlled challenges to a similar side chain and dissimilar side chain cephalosporin as compared to the side chain of their culprit to assess cross-reactivity The order of these two challenges is randomized between visit 2 and 3 and the order of whether a similar or dissimilar side chain cephalosporin is challenged first in visit 2 differentiates the comparator arms of this study In visit 4 subjects from both comparator arms will undergo a double-blind placebo-controlled challenge to a penicillin to assess cross-reactivity between cephalosporins and penicillins Completion of this penicillin challenge marks the end of participation for confirmed-allergic subjects Venipuncture and sample collection will occur at each visit
In the United States beta-lactam antibiotics are the leading cause of allergic reactions Cephalosporin antibiotics in particular are the most common cause of drug-induced anaphylaxis and perioperative allergy For penicillin allergy the mechanism of allergy and the antigenic determinants are known validated penicillin skin testing followed by drug challenge has a 100 negative predictive value to exclude an immunoglobulin IgE-mediated reaction For cephalosporin allergy the antigenic determinants and mechanism are not known and skin testing is not validated The diagnostic test characteristics of skin testing with native cephalosporins remain unclear with no sensitivity nor specificity reported Although beta-lactam cross-reactivity has been hypothesized to be from the similarity of the R1 side chains rather than the beta-lactam ring cross-reactivity estimates among beta-lactams vary Furthermore it is not known whether the variance in cross-reactivity is due to true allergy versus sensitization based on positive skin testing given that drug challenges were not performed on skin-test-positive patients While an IgE mechanism is assumed for cephalosporin allergy and supported by skin testing that has been positive the biology has yet to be characterized and some cephalosporin anaphylaxis can occur on the first exposure which is inconsistent with an IgE mechanism Given the complexity of cephalosporin structures and potential epitopes there may be several distinct biologic pathways involved in cephalosporin allergy Future diagnostics in cephalosporin allergy are reliant on determination of these biological pathways and finding key haptens
Aims
Current national practice guidelines related to cephalosporin allergy assessment are considered conditional and based on low-quality evidence The overall goal is to identify the optimal diagnostic approach to cephalosporin allergy and determine beta-lactam cross-reactivity while discovering the mechanism and antigenic determinants of cephalosporin allergy to advance future diagnostics The investigators will do this through a clinical trial that will generate empirical evidence through novel trial procedures double-blind skin testing and double-blind placebo-controlled drug challenges Specific aims are 1 To determine the optimal approach to cephalosporin allergy evaluation 2 To assess beta-lactam cross-reactivity in cephalosporin-allergic individuals and 3 To investigate the antigenic determinants and mechanism of cephalosporin allergy
Study Overview
Enrolled and consented subjects will attend visit 1 for baseline screening sample collection double-blind skin testing to a beta-lactam panel and a double-blind placebo-controlled challenge to their culprit cephalosporin antibiotic Results of the culprit cephalosporin challenge determine subjects study timeline Subjects confirmed as non-allergic to their culprit cephalosporin will return for visit 2 for venipuncture and blood collection ending their participation in the study Subjects who are confirmed as allergic to their culprit at visit 1 will return for three additional visits visits 2 and 3 will include double-blind placebo-controlled challenges to a similar side chain and dissimilar side chain cephalosporin as compared to the side chain of their culprit to assess cross-reactivity The order of these two challenges is randomized between visit 2 and 3 and the order of whether a similar or dissimilar side chain cephalosporin is challenged first in visit 2 differentiates the comparator arms of this study In visit 4 subjects from both comparator arms will undergo a double-blind placebo-controlled challenge to a penicillin to assess cross-reactivity between cephalosporins and penicillins Completion of this penicillin challenge marks the end of participation for confirmed-allergic subjects Venipuncture and sample collection will occur at each visit
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U01AI184071 | OTHER_GRANT | NIAID | None |