Impact of post-Acute respiratory distress syndrome COVID sedation on late neuroinflammation (PET-DEXDOCOVID)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Virus Diseases [C02]

Trial duration

completed 4 Sep 2025

Decision date (initial)

2024-10-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511898-30-00

EudraCT number

2020-004802-70

ClinicalTrials.gov

NCT04352348

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate whether treatment with dexmedetomidine at the end of sedation to prevent or treat delirium following post-COVID-19 ARDS reduces persistent neuroinflammation measured by an increase in the radio pharmaceutical DPA in the frontal lobes and detected using PET-MRI at 24 months (+24 months) after discharge from intensive care.

Secondary objectives 4

1. - To assess the effect of dexmedetomidine treatment on acquired neuro-cognitive damage using clinical assessment scores at 24 months (+24 months) after discharge from intensive care of patients hospitalised for ARDS with COVID-19 ;
2. - To evaluate the effect of dexmedetomidine treatment on neurocognitive lesions acquired with diffusion tensor brain MRI at 24 months (+24 months) after discharge from intensive care of patients hospitalised for ARDS with COVID-19 ;
3. - To assess the association between immunological, transcriptomic and epigenomic biological data likely to promote or protect against the persistence of a neuroinflammatory state at a distance from a severe COVID-19 infection 24 months (+24 months) after discharge from the intensive care unit.
4. - Identify clinical and pharmacological risk factors (in particular sedative treatments used for ventilatory weaning) for the development of late-onset neuroinflammation defined by an increase in DPA on PET-MRI in the frontal lobes and other regions of interest at 24 months (+24 months) after discharge from intensive care.

Conditions and MedDRA coding

Patients who survive a COVID ARDS in intensive care must be weaned off invasive mechanical ventilation as quickly as possible. 60% of these patients present with intensive care delirium, a serious event that causes excess mortality and potential acute and late complications, since 30% of patients who present with delirium develop cognitive sequelae. Severe neuroinflammation is considered to be one of the main pathophysiological mechanisms causing delirium during ventilatory weaning. In addition to its sedative properties, dexmedetomidine has neuroprotective effects. In certain experimental models, it reduces cerebral inflammation by acting directly on the microglial phenotype. The role of this chronic neuroinflammatory state on cognitive capacity and reserve is beginning to emerge in the literature, regardless of the initial stress (surgery, head injury or Alzheimer's-type dementia), and is therefore capable of influencing patients' quality of life. The assessment of this neuroinflammation using non-invasive tools would appear to be of prime importance in the management of post-COVID neuro injured patients, as well as the evaluation of potential neuroprotective agents such as dexmedetomidine.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. - Patients over the age of majority (age ≥ 18 years at the time of inclusion) and under 75 years of age
2. COVID-19 infection documented by nasopharyngeal PCR test.
3. - TPSO genotyping homozygous high affinity for [18F]-DPA-714 or heterozygous intermediate affinity for [18F]-DPA-714.
4. - Patient admitted to intensive care for ARDS following COVID infection requiring mechanical ventilation and deep sedation for at least 24 hours.
5. - Patient alive 24 months (+24 months) after discharge from intensive care unit
6. - Signature of free and informed consent
7. - Patient affiliated to a social security scheme, excluding AME (state medical aid)
8. For the group of patients exposed to dexmedetomidine : - Administration of dexmedetomidine for at least 24 hours during hospitalisation in intensive care.
9. For the group of patients not exposed to dexmedetomidine : - No administration of dexmedetomidine during hospitalisation in the intensive care unit.

Exclusion criteria 10

1. - Protected adults (under court protection, guardianship or curatorship)
2. - Pregnant or breast-feeding
3. - Contraindication to a PET or MRI scan
4. - Contraindication to the administration of the radiopharmaceutical [18F]-DPA-714
5. - Severe renal insufficiency (creatinine clearance < 30 mL/min)
6. - Serious neurological history on admission to the intensive care unit: o Cerebrovascular accident o Severe head trauma o Dementia with loss of autonomy
7. - New severe COVID infection of the ARDS type
8. - New severe bacterial infection of the severe sepsis type
9. - Severe surgical traumatism such as cranial trauma or polytraumatism
10. - Poor vaccine tolerance requiring hospitalisation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Persistent neuroinflammation is measured by the intensity of the [18F]-DPA-714 signal obtained in PET-MRI imaging at 24 months (+24 months) after discharge from intensive care on the 2 frontal lobes (freesurfer segmentation, the signal intensity being the ratio of the measurement made in the frontal lobes to that made in the cerebellar lobes. Standard fixation will be expressed as an indexed value relative to the control value.
2. The intensity of the [18F]-DPA-714 signal is the standard uptake value which will be measured in each region of interest (frontal lobes and cerebellar lobes = reference) and related to the quantity of radioactivity injected for the examination. The ratio of SUV in the frontal lobes to SUV in the cerebellar lobes will give us the radioligand uptake ratio for the area of interest.

Secondary endpoints 4

1. - To evaluate the effect of dexmedetomidine treatment on acquired neurocognitive damage using clinical assessment scores at 24 months (+24 months) after discharge from intensive care of patients hospitalised for ARDS with COVID-19 ;
2. - To evaluate the effect of dexmedetomidine treatment on neurocognitive lesions acquired with diffusion tensor brain MRI at 24 months (+24 months) after discharge from intensive care following COVID ARDS.
3. - To assess the association between immunological, transcriptomic and epigenomic biological data likely to promote or protect against the persistence of a neuroinflammatory state remote from a severe COVID-19 infection 24 months (+24 months) after discharge from intensive care.
4. - To identify the clinical and pharmacological risk factors (in particular the sedative treatments used for ventilatory weaning) for the occurrence of late neuroinflammation defined by an increase in DPA on PET-MRI in the frontal lobes and other regions of interest at 24 months (+24 months) after discharge from intensive care

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinator investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinator investigator

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications