Gonorrhoea Resistance Assessment by Nucleic Acid Detection (GRANDII)

Sponsor

The University of Queensland (Other)

Overall Status

Unknown status

CT.gov ID

NCT04268342

Collaborator

Kirby Institute (Other), Monash University (Other), South Australian Health and Medical Research Institute (Other), University of Melbourne (Other), University of California, Los Angeles (Other), Griffith University (Other), Queensland Health (Other), SydPath - St Vincent's Pathology (Other), SpeeDx Pty. Ltd. (Other), NSW Health Pathology (Other), University of Sydney (Other)

3,024

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Nine sexual health clinical services across Australia and their associated pathology testing laboratories are implementing a new management program for gonorrhoea infection. The services are implementing the use of gonorrhoea drug resistance testing as part of routine clinical and laboratory practice, where drug resistance test results are provided to clinicians quickly to guide choice of antibiotic therapy. Clinicians will identify gonorrhoea infection that is ciprofloxacin susceptible so that it can be treated with ciprofloxacin therapy, rather than ceftriaxone.

Condition or Disease	Intervention/Treatment	Phase
Drug Resistance, Microbial Antimicrobial Stewardship Gonorrhea	Other: Resistance guided treatment for gonorrhoea infection	N/A

Detailed Description

This study aims to demonstrate the feasibility of a new approach to antibiotic stewardship based on individually tailored antibiotic prescribing. Nine sexual health clinical services from across Australia with high caseloads of gay and bisexual men and Aboriginal and Torres Strait Islander clients, will adopt a new management practice for gonorrhoea infection involving provision of tailored antibiotic therapy by clinicians at the time of gonorrhoea diagnosis and treatment, guided by the results of resistance testing. The services are implementing the use of gonorrhoea drug resistance testing as part of routine clinical and laboratory practice, where drug resistance test results are provided to clinicians quickly to guide choice of antibiotic therapy. This differs from existing practice where the prolonged turn-around times for drug resistance testing results mean clinicians must prescribe drug therapy without knowing these results. This can lead to increasing levels of drug resistance to ceftriaxone.

The drug resistance test used in the new program detects genetic material (nucleic acids). It was developed and validated in Australia and is as accurate as existing culture-based drug resistance testing but provides quicker results. Patients treated presumptively at their first clinic visit will be treated with standard of care ceftriaxone. However, for cases treated at the return visit, clinicians will identify gonorrhoea infection that is ciprofloxacin susceptible so that it can be treated with ciprofloxacin therapy, rather than ceftriaxone. This will preserve ceftriaxone for situations where it must be used as the only effective drug available. Established patient follow-up procedures at clinical services will confirm that treatment has been successful.

Quantitative data from the clinical and laboratory services in the study will be used to assess the cure rate in gonorrhoea cases within the new management program versus standard care. The proportion of all cases treated with ceftriaxone will be also be assessed which will help illustrate the impact of the new management program.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

3024 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

The stepped-wedge design used for this program evaluation will allow comparison of the standard practice for gonorrhoea management based on injected ceftriaxone (at sites in the control phase) with individualised treatment based on drug resistance testing (at sites in the implementation phase). The unit of randomisation is each group of three clinical services.The stepped-wedge design used for this program evaluation will allow comparison of the standard practice for gonorrhoea management based on injected ceftriaxone (at sites in the control phase) with individualised treatment based on drug resistance testing (at sites in the implementation phase). The unit of randomisation is each group of three clinical services.

Masking:

Single (Investigator)

Masking Description:

The clinical services will be randomized to the intervention using a computer generated number sequence by the study statistician who is blinded to the sites.

Primary Purpose:

Treatment

Official Title:

Gonorrhoea Resistance Assessment by Nucleic Acid Detection: A Program Evaluation

Anticipated Study Start Date :

Mar 2, 2020

Anticipated Primary Completion Date :

Mar 2, 2021

Anticipated Study Completion Date :

Aug 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Standard care When clinical services are in the standard case phase of the study, all cases of gonorrhoea infection diagnosed at those services will be managed according to current standard of care management guidelines i.e. all cases of gonorrhoea infection will be treated with ceftriaxone by injection plus oral azithromycin tablets as first line therapy, regardless of whether the treatment is given at the initial clinic or the return clinic visit.
Active Comparator: Implementation When clinical services are assigned to the implementation phase, first line treatment for gonorrhoea infection for patients treated at their first clinic visit will remain the same as it is currently: ceftriaxone by injection plus oral azithromycin tablets. However, patients who are not treated presumptively will be treated at their return visit on the basis of the drug resistance test results. Patients with gonorrhoea infection that is shown to be susceptible to ciprofloxacin will be treated with oral ciprofloxacin therapy when they return for review at clinical services in the implementation phase. Patients with gonorrhoea infection that is not susceptible to ciprofloxacin or with an indeterminate ciprofloxacin result will be treated with ceftriaxone by injection.	Other: Resistance guided treatment for gonorrhoea infection For cases of gonorrhoea infection treated at the return visit, a nucleic acid assay will be used to determine individual eligibility for ciprofloxacin treatment

Arm

Intervention/Treatment

No Intervention: Standard care

When clinical services are in the standard case phase of the study, all cases of gonorrhoea infection diagnosed at those services will be managed according to current standard of care management guidelines i.e. all cases of gonorrhoea infection will be treated with ceftriaxone by injection plus oral azithromycin tablets as first line therapy, regardless of whether the treatment is given at the initial clinic or the return clinic visit.

Active Comparator: Implementation

When clinical services are assigned to the implementation phase, first line treatment for gonorrhoea infection for patients treated at their first clinic visit will remain the same as it is currently: ceftriaxone by injection plus oral azithromycin tablets. However, patients who are not treated presumptively will be treated at their return visit on the basis of the drug resistance test results. Patients with gonorrhoea infection that is shown to be susceptible to ciprofloxacin will be treated with oral ciprofloxacin therapy when they return for review at clinical services in the implementation phase. Patients with gonorrhoea infection that is not susceptible to ciprofloxacin or with an indeterminate ciprofloxacin result will be treated with ceftriaxone by injection.

Other: Resistance guided treatment for gonorrhoea infection

For cases of gonorrhoea infection treated at the return visit, a nucleic acid assay will be used to determine individual eligibility for ciprofloxacin treatment

Outcome Measures

Primary Outcome Measures

Cure rate [At 12 months after implementation commences]
The proportion of gonorrhoea cases treated at the return visit with a negative test of cure within 2-4 weeks within the new management program versus standard care

Secondary Outcome Measures

Change in ceftriaxone use [18 months after implementation commences]
The proportion of gonorrhoea cases treated with ceftriaxone at the return visit
Acceptability [1-18 months after implementation commences]
The acceptability of the new management program to clinic and laboratory staff and stakeholders will be assessed through a qualitative research study design. Service staff and external stakeholders will be selected purposively to take part in semi-structured in-depth interviews at different stages of the study. Sampling will be informed by data saturation. All interviews will be audio-recorded and transcribed verbatim. Qualitative data will be analysed using a system of thematic 'open' and 'axial' coding. Findings will be descriptive.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients diagnosed with gonorrhoea infection at the return visit

Exclusion Criteria:

Patients for whom ciprofloxacin is contraindicated

Contacts and Locations

Locations

No locations specified.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

The University of Queensland

ClinicalTrials.gov Identifier:

NCT04268342

Other Study ID Numbers:

17/180

First Posted:

Feb 13, 2020

Last Update Posted:

Feb 13, 2020

Last Verified:

Feb 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Gonorrhea

Study Results

No Results Posted as of Feb 13, 2020