FAPI PET/CT to Detect Fibroblast Activity in Non-resolving ARDS (FAPI ARDS)

[68Ga]-FAPI PET/CT to Detect Fibroblast Activity in Non-resolving ARDS, a Feasibility Study.

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: ARDS (Moderate or Severe)
• Intervention / Treatment: Diagnostic test: PET

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.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9715JK
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient outcome - ICU stay	Pulmonary FAP expression, measured by [68Ga]-FAPI PET/CT, correlated to 28 days of ICU stay.	From inclusion until the end of the study (28 days after inclusion)
Patient outcome - 28 days mortality	Pulmonary FAP expression, measured by [68Ga]-FAPI PET/CT, correlated to 28 days mortality.	From inclusion until end of the study (28 days after inclusion)
Patient outcome - VFD-28	Pulmonary FAP expression, measured by [68Ga]-FAPI PET/CT, correlated to ventilation free days of 28 days (VFD-28)	From inclusion until end of the study (28 days after inclusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic ECM and inflammatory markers	Pulmonary FAP expression, measured by [68Ga]-FAPI PET/CT, correlated to extra cellular matrix and inflammatory parameters on the day of PET/CT.	On day of PET/CT
Respiratory ECM and inflammatory markers	Pulmonary FAP expression, measured by [68Ga]-FAPI PET/CT, correlated to BAL extra cellular matrix, inflammatory parameters and cellular phenotypes	within 48 hours before or after PET/CT
Respiratory scRNA	Around the time of the PET/CT a broncho alveolair lavage will be performed collecting respiratory system cells which will be analysed using scRNA analysis.	within 48 hours before or after PET/CT

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal brush scRNA	scRNA of the BAL will be correlated to the scRNA of the nasal brush.	48 hours before or after the PET/CT

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: November 13, 2024
• First Submitted That Met QC Criteria: November 13, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: PET/CT; ARDS; respiratory failure; FAPI
• Other Study ID Numbers: 11304 (DAIDS ES); CCMO (Registry Identifier: NL83114.042.22); 2024-517257-27-00 (Ctis); 2022-003701-29 (EudraCT Number); Review board UMCG (Registry Identifier: 2022/577)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No