Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Use of Penicillin Allergy Clinical Decision Rule to Enable Direct Oral Penicillin Challenge (PALACE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04454229
Recruitment Status : Not yet recruiting
First Posted : July 1, 2020
Last Update Posted : January 8, 2021
Sponsor:
Information provided by (Responsible Party):
Ana Copaescu, Austin Health

Brief Summary:
Whilst validated tools exist to enable inpatient penicillin assessment and de-labelling, limited evidence is available regarding the safety and efficacy in the outpatient clinic. The ability to deliver point-of-care penicillin allergy testing for a large cohort of patients, without skin testing, will improve patient access to testing and utilization of preferred penicillin antibiotics.

Condition or disease Intervention/treatment Phase
Hypersensitivity, Immediate Hypersensitivity, Delayed Hypersensitivity Response Other: Direct oral penicillin challenge Other: Standard of care Not Applicable

Detailed Description:
Patient-reported penicillin allergies result in poor health outcomes for patients and drive inappropriate antibiotic prescribing, antimicrobial resistance and healthcare costs. Our group has internally and externally validated a novel penicillin allergy clinician decision rule (PEN-FAST) that is able to identify low risk penicillin allergies with a negative predictive value of 96% (95%; 94-98%). Therefore, whilst validated tools exist to enable inpatient penicillin assessment and de-labelling, limited evidence is available regarding the safety and efficacy in the outpatient clinic. The ability to deliver point-of-care penicillin allergy testing for a large cohort of patients, without skin testing, will improve patient access to testing and utilization of preferred penicillin antibiotics.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 380 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Direct oral challenge in patients with PEN-Fast less than 3

Eligible patients referred to the outpatient clinic reporting a penicillin allergy will be identified and assessed with a standard clinical history and the calculation of the PEN-FAST score. PEN-FAST is a three-point clinical assessment tool recently externally validated in a multicenter study, with a PEN-FAST score of < 3 associated with 96.7% negative predictive value.

Intervention:

The patient will receive a single dose of oral penicillin, following baseline vital signs (i.e. temperature, heart rate, blood pressure, respiratory rate, skin check).

Nursing staff will repeat vital signs as needed and after oral challenge while observing for signs of an immune mediated adverse reaction.

If at any stage an antibiotic associated adverse event is noted, standard of care treatment is offered by the attending clinicians (ex. adrenalin for immediate hypersensitivity reaction).

Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: The Use of Penicillin Allergy Clinical Decision Rule to Enable Direct Oral Penicillin Challenge - An International Multicenter Randomized Control Trial - The PALACE Study
Estimated Study Start Date : February 15, 2021
Estimated Primary Completion Date : August 15, 2021
Estimated Study Completion Date : August 15, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy
Drug Information available for: Penicillins

Arm Intervention/treatment
Experimental: Direct oral antibiotic challenge
Direct oral antibiotic (penicillin) challenge in patients with PEN-Fast less than 3.
Other: Direct oral penicillin challenge
The patient will receive a single dose of oral penicillin, following baseline vital signs.

Active Comparator: Standard of care
Standard of care: skin testing and, if negative, oral challenge.
Other: Standard of care
Routine management as per the treating clinicians that include skin prick and intradermal beta-lactam testing, followed by oral penicillin challenge in the setting of negative skin testing.




Primary Outcome Measures :
  1. The difference in the proportion of positive oral challenges (i.e. immune-mediated reaction) [ Time Frame: up to 48H after oral challenge ]

Secondary Outcome Measures :
  1. Proportion of patients referred to the outpatient allergy clinic that are eligible for intervention (i.e randomization) as per protocol [Eligibility to screened ratio] [ Time Frame: Before randomization ]
  2. Feasibility of recruitment defined as the proportion of patients consenting to participate in the study as per protocol from eligible patients. [Recruitment to eligibility ratio]. [ Time Frame: Before randomization ]
  3. Feasibility of intervention delivery defined as the proportion of patients randomized to the intervention arm who had the intervention delivered as per protocol. [Intervention to recruitment ratio] [ Time Frame: Before randomization ]
  4. The proportion of patients with a penicillin allergy who experience an antibiotic associated immune mediated adverse event OR severe adverse drug reaction as per protocol definitions. [ Time Frame: Up to 48h after the drug challenge ]
  5. The proportion of patients that will respect the protocol (protocol compliance) [ Time Frame: Up to 48h after the drug challenge ]
  6. Proportion of patient with positive Penicillin Skin Testing [ Time Frame: Up to 48h after the drug challenge ]
  7. Proportion of patients with non-immune mediated positive oral challenges [ Time Frame: Up to 48h after the drug challenge ]
  8. Proportion of patients with severe adverse reaction - anaphylaxis/death [ Time Frame: Up to 48h after the drug challenge ]
  9. Time from randomization to delabelling [ Time Frame: Up to 48h after the drug challenge ]
  10. Number of appointments required for Penicillin delabelling [ Time Frame: Up to 48h after the drug challenge ]
  11. Assessment with the Drug Hypersensitivity Quality of Life Questionnaire [ Time Frame: Up to 48h after the drug challenge ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult patients referred to the outpatient allergy clinic for a penicillin allergy history;
  2. Willing and able to give consent.

Exclusion Criteria:

  1. Patient age is < 18 years;
  2. Patients with a PEN-FAST score ?3
  3. Pregnancy;
  4. Any other illness that, in the investigator's judgement, will substantially increase the risk associated with subject's participation in this study;
  5. Patients with history of type A adverse drug reaction, drug-associated anaphylaxis, idiopathic urticaria/anaphylaxis, mastocytosis, serum sickness, blistering skin eruption or acute interstitial nephritis;
  6. Patients with a concurrent history of immune-mediated cephalosporin allergy;
  7. Patients where the allergy history was not able to be confirmed with patient;
  8. Patients on concurrent antihistamine therapy;
  9. Patients receiving more than stress dose steroids (i.e. > 50mg QID hydrocortisone [or steroid equivalent]).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04454229


Contacts
Layout table for location contacts
Contact: Ana Copaescu, MD +610466067000 ana.copaescu@gmail.com
Contact: Jason Trubiano, MD PhD +61394966709 Jason.TRUBIANO@austin.org.au

Locations
Layout table for location information
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Contact: Elizabeth Phillips, MD       elizabeth.j.phillips@vumc.org   
Contact: Cosby Stone, MD, MPH       cosby.a.stone@vumc.org   
Australia, Victoria
Austin Health
Heidelberg, Victoria, Australia, 3084
Contact: Ana Copaescu, MD    0466067000    Ana.copaescu@austin.org.au   
Contact: Jason Trubiano, MD PhD    (03) 94966709    Jason.trubiano@austin.org.au   
Peter MacCallum Cancer Center
Melbourne, Victoria, Australia, 3000
Contact: Jason Trubiano, MD PhD    (03) 94966709    Jason.trubiano@austin.org.au   
Contact: Ana Copaescu, MD    0466067000    Ana.copaescu@austin.org.au   
Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3000
Contact: Joseph De Luca, MD    (03) 93493199    Joseph.DeLuca@mh.org.au   
Canada, Quebec
Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, Canada, H2X 3E4
Contact: Philippe Bégin, MD PhD       philippe.begin@umontreal.ca   
McGill University Health Centre (MUHC)
Montreal, Quebec, Canada, H3G 1A4
Contact: Christos Tsoukas, MD       christos.tsoukas@mcgill.ca   
Sponsors and Collaborators
Austin Health
Publications of Results:
Layout table for additonal information
Responsible Party: Ana Copaescu, Investigator, Allergy-Immunology Fellow, Austin Health
ClinicalTrials.gov Identifier: NCT04454229    
Other Study ID Numbers: PALACE1
First Posted: July 1, 2020    Key Record Dates
Last Update Posted: January 8, 2021
Last Verified: January 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Ana Copaescu, Austin Health:
penicillin
Low Risk allergy
direct oral challenge
standard of care
outpatient clinic
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity, Delayed
Immune System Diseases
Penicillins
Anti-Bacterial Agents
Anti-Infective Agents