Aspergillosis, Invasive Pulmonary Clinical Trial
— AzorManOfficial title:
PCR Based Detection of Azole Resistance in A. Fumigatus to Improve Patient Outcome. A Prospective Multicenter Observational Study.
NCT number | NCT03121235 |
Other study ID # | MEC-2016-664 |
Secondary ID | |
Status | Completed |
Phase | |
First received | |
Last updated | |
Start date | April 20, 2017 |
Est. completion date | March 20, 2022 |
Verified date | March 2022 |
Source | Erasmus Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
A standard treatment protocol for invasive aspergillosis (IA) will be implemented in several academic hematology centers in the Netherlands in which a diagnostic test demonstrating azole resistance by multiplex real-time polymerase chain reaction will guide the choice of appropriate antifungal treatment. Objectives: 1. Improve the outcome of patients infected with azole resistant A. fumigatus by the early detection of Resistance Associated Mutations (RAMs) and with this the earlier initiation of the most appropriate therapy. 2. Monitor the prevalence of invasive aspergillosis due to strains carrying the TR34/L98H or the TR46/T289A/Y121F resistance associated mutations in the Netherlands.
Status | Completed |
Enrollment | 320 |
Est. completion date | March 20, 2022 |
Est. primary completion date | December 31, 2021 |
Accepts healthy volunteers | |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Patient with underlying hematological disease - Patient will undergo/underwent BAL sampling for suspected invasive fungal infection - BAL samples should be submitted to the local microbiology lab for fungal culture and for galactomannan detection. - The treating physician is planning to start voriconazole, isavuconazole or posaconazole after the BAL has been sampled while waiting for the culture or PCR results of the BAL sample or has already started voriconazole or posaconazole before BAL sampling. Exclusion Criteria: - A potential subject who meets any of the following criteria will be excluded from participation in this study: - Antifungal therapy was started >120hours prior to BAL sampling (*) - Antifungal prophylaxis with posaconazole or voriconazole for >5 days within the 2 weeks preceding BAL sampling - Antifungal prophylaxis with itraconazole and at least half of the plasma itraconazole/hydroxy-itraconazole levels that were measured through therapeutic drug monitoring were above the minimum effective plasma concentration of 0.5mg/L (parental compound only, HLPC assay method). The minimum effective plasma concentration of 0.5mg/L for itraconazole has been established by the ECIL 6 meeting with a recommendation AII. (*) Patients that develop new pulmonary infiltrates during antifungal prophylaxis (systemic azoles or aerosolized amphotericin B) can be included. |
Country | Name | City | State |
---|---|---|---|
Netherlands | Academisch Medisch Centrum | Amsterdam | |
Netherlands | VU Medisch Centrum | Amsterdam | |
Netherlands | Universitair Medisch Centrum Groningen | Groningen | |
Netherlands | Leids Universitair Medisch Centrum | Leiden | |
Netherlands | Maastricht Universitair Medisch Centrum + | Maastricht | |
Netherlands | Radboud Medisch Universitair Centrum | Nijmegen | |
Netherlands | Erasmus Medical Center | Rotterdam | |
Netherlands | Universitair Medisch Centrum Utrecht | Utrecht |
Lead Sponsor | Collaborator |
---|---|
Erasmus Medical Center | Gilead Sciences |
Netherlands,
Chong GL, van de Sande WW, Dingemans GJ, Gaajetaan GR, Vonk AG, Hayette MP, van Tegelen DW, Simons GF, Rijnders BJ. Validation of a new Aspergillus real-time PCR assay for direct detection of Aspergillus and azole resistance of Aspergillus fumigatus on bronchoalveolar lavage fluid. J Clin Microbiol. 2015 Mar;53(3):868-74. doi: 10.1128/JCM.03216-14. Epub 2015 Jan 7. — View Citation
Chong GM, van der Beek MT, von dem Borne PA, Boelens J, Steel E, Kampinga GA, Span LF, Lagrou K, Maertens JA, Dingemans GJ, Gaajetaan GR, van Tegelen DW, Cornelissen JJ, Vonk AG, Rijnders BJ. PCR-based detection of Aspergillus fumigatus Cyp51A mutations on bronchoalveolar lavage: a multicentre validation of the AsperGenius assay® in 201 patients with haematological disease suspected for invasive aspergillosis. J Antimicrob Chemother. 2016 Dec;71(12):3528-3535. Epub 2016 Aug 15. — View Citation
Mavridou E, Brüggemann RJ, Melchers WJ, Mouton JW, Verweij PE. Efficacy of posaconazole against three clinical Aspergillus fumigatus isolates with mutations in the cyp51A gene. Antimicrob Agents Chemother. 2010 Feb;54(2):860-5. doi: 10.1128/AAC.00931-09. Epub 2009 Nov 16. — View Citation
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Verweij PE, Ananda-Rajah M, Andes D, Arendrup MC, Brüggemann RJ, Chowdhary A, Cornely OA, Denning DW, Groll AH, Izumikawa K, Kullberg BJ, Lagrou K, Maertens J, Meis JF, Newton P, Page I, Seyedmousavi S, Sheppard DC, Viscoli C, Warris A, Donnelly JP. International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus. Drug Resist Updat. 2015 Jul-Aug;21-22:30-40. doi: 10.1016/j.drup.2015.08.001. Epub 2015 Aug 7. — View Citation
Verweij PE, Chowdhary A, Melchers WJ, Meis JF. Azole Resistance in Aspergillus fumigatus: Can We Retain the Clinical Use of Mold-Active Antifungal Azoles? Clin Infect Dis. 2016 Feb 1;62(3):362-8. doi: 10.1093/cid/civ885. Epub 2015 Oct 20. Review. — View Citation
Verweij PE, Lestrade PP, Melchers WJ, Meis JF. Azole resistance surveillance in Aspergillus fumigatus: beneficial or biased? J Antimicrob Chemother. 2016 Aug;71(8):2079-82. doi: 10.1093/jac/dkw259. Review. — View Citation
Verweij PE, Zhang J, Debets AJM, Meis JF, van de Veerdonk FL, Schoustra SE, Zwaan BJ, Melchers WJG. In-host adaptation and acquired triazole resistance in Aspergillus fumigatus: a dilemma for clinical management. Lancet Infect Dis. 2016 Nov;16(11):e251-e260. doi: 10.1016/S1473-3099(16)30138-4. Epub 2016 Sep 13. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of antifungal treatment failure | Incidence of antifungal treatment failure in patients with the presence of RAM detected by the AsperGenius® resistance PCR. This incidence will be compared with a fixed failure rate set at 75%, based on the observed treatment failure in patients treated with voriconazole that were shown to carry azole resistant A. fumigatus. | 12 weeks | |
Secondary | Demonstrate that early detection of azole resistance reduces the overall mortality. | This will be compared with a fixed mortality of 50%. | 6 weeks | |
Secondary | Demonstrate that a step down to oral posaconazole is a reasonable treatment option in patients that have responded to at least 2 weeks of IV antifungal therapy. | Posaconazole step down therapy will be considered effective if <35% of the patients treated with posaconazole oral monotherapy show progression of their invasive aspergillosis after documented response after at least 14 days of IV antifungal therapy. | 12 weeks | |
Secondary | Comparison of antifungal treatment failure in patients with the presence of RAM. | A group that received appropriate antifungal therapy soon will be compared with a group that received treatment late. | 24 weeks |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
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