Clinical trial NCT06691464: FAPI PET/CT to Detect Fibroblast Activity in Non-resolving ARDS
Official title: [68Ga]-FAPI PET/CT to Detect Fibroblast Activity in Non-resolving ARDS, a Feasibility Study.
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: ARDS (Moderate or Severe)
Keywords: ARDS
respiratory failure
FAPI
PET/CT
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2024-11-15
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to the ICU who are mechanically ventilated and fulfil the ARDS criteria for more than 5 days.

Brief summary: Of patients requiring mechanical ventilation in the ICU 23% meet criteria of the Acute Respiratory Distress Syndrome (ARDS). Mortality of this syndrome remains high (35-46%) in moderate and severe ARDS. In patients not recovering from ARDS, fibroblasts seem to play an important role. However, the effect of fibroblast activity on the lack of pulmonary recovery is not fully understood. The new PET tracer \[68Ga\]FAPI-46 (FAPI) allows for imaging of activated fibroblasts. The aim of this study is to explore the pulmonary fibroblast activity, measured with the FAPI PET/CT, in patients with non-resolving ARDS.

Detailed description: Of patients requiring mechanical ventilation in the ICU 23% meet criteria of the Acute Respiratory Distress Syndrome (ARDS). Mortality of this syndrome is high (35-46%) in moderate and severe ARDS. The fibroproliferative phase plays an important role in patients not recovering from ARDS. Bronchoalveolar lavage (BAL) can be used to investigate this process. However, quantitative assessment using BAL of fibroblast activity in both lungs is invasive, indirect and has yielded inconsistent results. This has precluded clinical utility. New methods to assess fibroblast activity in ARDS are therefore needed. A novel tool is PET/CT with the tracer \[68Ga\]-FAPI-46. \[68Ga\]-FAPI PET has the ability for reproducible and non-invasive measurement of fibroblast activity.

Objective:

1. To relate pulmonary fibroblast activity in non-resolving ARDS, measured by FAPI-PET/CT, to 28 day mortality, ventilator-free days and alive at 28 days (VFD-28) and ICU length of stay.
2. To study the relationship between pulmonary fibroblast activity and systemic fibrotic and inflammatory biomarker.
3. To relate the pulmonary fibroblast activity on \[68Ga\]FAPI PET/CT with respiratory cell phenotypes and fibrotic and inflammatory mediators collected via bronchoalveolar lavage (BAL).

Study design: This is a single center prospective observational feasibility study. We will include 20 ventilated patients with non-resolving ARDS. All mechanically ventilated patients in the ICU will be screened daily for ARDS. When ARDS is present for 5 consecutive days, patients will be included. Within 7 days after inclusion a \[68Ga\]FAPI-46 PET/CT scan will be performed. Within 48 hours of the PET/CT a broncho alveolar lavage and a nasal brush, will be performed. Blood will be drawn at inclusion and every 3rd day, as well as the day of the PET/CT. Daily registration of ventilatory and circulatory parameters, as well as clinical blood parameters, will be collected.

End of study: The study will end when the patient has died, is discharged from the ICU or after 28 days.

Eligibility criteria: Inclusion Criteria:

* Mechanically ventilated
* Patient meets the criteria for non-resolving ARDS as at day 5 of the ARDS diagnosis one or more of the following criteria is true:

  * P/F ratio \<200 mmHg
  * Positive End Expiratory Pressure (PEEP) of 12 cmH2O or more
  * Static lung compliance of \< 50 ml/cmH2O
* Deemed safe for transport by attending clinician (staff Intensivist)
* Informed consent signed by patient or legal representative

In case of COVID-19 a SARS-CoV-2 PCR CT of \> 30 is required.

Exclusion Criteria:

* Women who are pregnant or breastfeeding
* Inability to attain informed consent
* Too unstable for transport as judged by the treating staff intensivist

Primary outcomes:
measure: Patient outcome - ICU stay
timeFrame: From inclusion until the end of the study (28 days after inclusion)
measure: Patient outcome - 28 days mortality
timeFrame: From inclusion until end of the study (28 days after inclusion)
measure: Patient outcome - VFD-28
timeFrame: From inclusion until end of the study (28 days after inclusion)
Secondary outcomes:
measure: Systemic ECM and inflammatory markers
timeFrame: On day of PET/CT
measure: Respiratory ECM and inflammatory markers
timeFrame: within 48 hours before or after PET/CT
measure: Respiratory scRNA
timeFrame: within 48 hours before or after PET/CT
Other outcomes:
measure: Nasal brush scRNA
timeFrame: 48 hours before or after the PET/CT
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
References: