Clinical trial NCT04720144: Breakthrough Invasive Mold Infections Under Posaconazole Prophylaxis (BIMI)
Official title: Multicenter Case-control Study of Breakthrough Invasive Mold Infections Under Posaconazole Prophylaxis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Invasive Mold Infections
Breakthrough Invasive Mold Infections
Hematologic Malignancy
Hematologic Diseases
Keywords: Posaconazole
Antifungal prophylaxis
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
First posted: 2021-01-22
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adults diagnosed with hematologic malignancies under posaconazole prophylaxis for one of the above mentionned reasons.

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Epidemiological description of bIMI
timeFrame: At inclusion
measure: Assessment of the risk factors of bIMI
timeFrame: At inclusion
Secondary outcomes:
measure: Assessment of the impact of bIMI on overall mortality
timeFrame: 6 weeks and 12 weeks after inclusion
measure: Assessment of factors influencing outcomes of bIMI
timeFrame: 6 weeks and 12 weeks after inclusion
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
city: Köln
country: Germany
facility: University Hospital Cologne
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Fribourg
country: Switzerland
facility: Hôpital Cantonal de Fribourg
city: Geneva
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG)
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St.Gallen
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Frederic Lamoth
role: PRINCIPAL_INVESTIGATOR
References: