Breakthrough Invasive Mold Infections Under Posaconazole Prophylaxis (BIMI)

Hematologic Malignancy Clinical Trial

— BIMI  

Official title:

Multicenter Case-control Study of Breakthrough Invasive Mold Infections Under Posaconazole Prophylaxis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04720144
• Other study ID #: 2020-01719
• Status: Recruiting
• Start date: October 1, 2020
• Est. completion date: September 30, 2022

Study information

• Verified date: February 2021
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: Frederic Lamoth
• Phone: +41213141111
• Email: frederic.lamoth[@]chuv.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Invasive mold infections (IMI) mainly affect patients with hematologic malignancies receiving intensive chemotherapy or after hematopoietic stem cell transplantation (HSCT). Prolonged neutropenia after remission induction chemotherapy (>10 days duration) and continuous immunosuppression in the context of prevention or therapy of graft versus host disease (GVHD) for HSCT recipients (first 100 days post-transplantation and thereafter if GVHD is present) are considered as periods at high risk of IMI.

Posaconazole prophylaxis is prescribed according to current guidelines to reduce the occurrence of IMI. Nevertheless, breakthrough IMI (bIMI), i.e. IMI occurring under mold-active prophylaxis, are still observed.

The investigators hypothesized that the epidemiology of bIMI (under posaconazole prophylaxis) differs from that of IMI occurring in the absence of mold-active antifungal prophylaxis. Because bIMI are rare events since the introduction of posaconazole prophylaxis, epidemiological data of bIMI are scarce.

This study aims to i) describe the epidemiology, clinical features, treatment and outcome of bIMI, ii) assess the causes of bIMI, iii) determine potential risk factors associated with the developllement of bIMI iv) assess the impact of bIMI on overall mortality.

Design

Retrospective and prospective, observational, case-control, multicenter, international study.

The retrospective part will enroll previously identified bIMI cases and control cases (1:2) over the last five years: October 1st 2015 to September 30st 2020.

The prospective part will enroll bIMI cases and control cases (1:2) occurring over a two-year period: October 1st 2020 to September 30st 2022.

Setting

The aim is to enroll 10 to 15 European centers with dedicated units for hematologic cancer patients. Currently, six centers have confirmed their participation (from Switzerland and Germany).

Study Population

Adult (≥ 18 years old) patients with a hematologic malignancy receiving posaconazole prophylaxis during induction, consolidation or re-induction chemotherapy or after HSCT.

Cases : patients receiving posaconazole prophylaxis for at least 7 days and diagnosed with bIMI proven or probable according to EORTC-MSGERC.

Controls: patients receiving posaconazole prophylaxis for at least 7 days, without diagnosis of bIMI possible, probable or proven according to EORTC-MSGERC.

The objective is to enroll about 100 bIMI cases and 200 controls.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: September 30, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cases:

Adult (= 18 years old) patients with a hematologic malignancy receiving posaconazole prophylaxis (oral tablets or IV administration) for:

i) Induction, consolidation or re-induction chemotherapy for acute leukemia or myelodysplastic syndrome (i.e. expected duration of neutropenia post-chemotherapy of = 10 days)

OR

ii) Allogeneic hematopoietic stem cell transplant recipients during the post-transplantation phase (100-day post-transplantation) or later in case of intensified immunosuppression for moderate to severe graft vs host disease (GVHD).

AND

iii) Being diagnosed with proven or probable bIMI according to the EORTC-MSG classification (10) while on continuous posaconazole prophylaxis for at least 7 days.

• Controls:

For each bIMI case, we will include 2 control cases fulfilling the following criteria:

i) Receiving continuous posaconazole prophylaxis for at least 7 days

ii) No diagnosis of proven, probable or possible IMI according to EORTC-MSG classification (10) during the entire hospital stay.

And matched to bIMI cases according to the following criteria:

iii) Hospitalization in the same ward within the same year (+/- 12 months interval)

iv) Same underlying condition related to hematologc cancer: a) HSCT within 100 days post-engraftment, b) HSCT > 100 days post-engraftment with intensified immunosuppressive regimen for severe GVHD, c) induction chemotherapy for acute myeloid or lymphoid leukemia, or myelodysplastic syndrome, d) other hematologic disorders (e.g. aplastic anemia) with prolonged neutropenia and/or immunosuppressive regimen.

Exclusion Criteria:

• Patients with a diagnosis of possible IMI according to the EORTC-MSG classification.

• Patients with a positive fungal biomarker in serum (e.g. galactomannan or beta-glucan) in the absence of clinical or radiological criteria of IMI according to the EORTC-MSG classification.

Related Conditions & MeSH terms

• Breakthrough Invasive Mold Infections
• Communicable Diseases
• Hematologic Diseases
• Hematologic Malignancy
• Hematologic Neoplasms
• Infection
• Invasive Mold Infections

Locations

Country	Name	City	State
Austria	Medical University of Innsbruck	Innsbruck
Germany	University Hospital Cologne	Köln
Switzerland	Universitätsspital Basel	Basel
Switzerland	Inselspital Bern	Bern
Switzerland	Hôpital Cantonal de Fribourg	Fribourg
Switzerland	Hôpitaux Universitaires de Genève (HUG)	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne
Switzerland	Kantonsspital St.Gallen	Saint Gallen

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Vaudois

Countries where clinical trial is conducted

Austria,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epidemiological description of bIMI	Assessment of the cause of bIMI (intrinsically resistant mold pathogen vs susceptible mold pathogen but insufficient posaconazole serum concentration vs unknown); Description of clinical features, treatment and outcome of bIMI	At inclusion
Primary	Assessment of the risk factors of bIMI	• Univariate and multivariate analyses of the parameters associated with an increased risk of bIMI (in particular, the association of a threshold of posaconazole concentration and bIMI) by comparison of bIMI cases with controls (posaconazole prophylaxis and no bIMI)	At inclusion
Secondary	Assessment of the impact of bIMI on overall mortality	• Comparison of mortality rate (6 and 12 weeks) between bIMI and control cases.	6 weeks and 12 weeks after inclusion
Secondary	Assessment of factors influencing outcomes of bIMI	• Univariate and multivariate analysis of predictors of mortality (6 and 12 weeks) among bIMI cases.	6 weeks and 12 weeks after inclusion