NCT03371498: ProCoCo

Procollagen-3 Driven Corticosteroids for Persistent Acute Respiratory Distress Syndrome

Terminated Phase 3 Last updated 3 January 2024

What this trial tests

Phase 3 trial testing Methylprednisolone in Persistent ARDS in 21 participants. Terminated before completion.

Timeline

27 December 2018

Primary endpoint
29 November 2023

29 November 2023

Quick facts

Lead sponsor	Assistance Publique Hopitaux De Marseille
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	21
Start date	27 December 2018
Primary completion	29 November 2023
Estimated completion	29 November 2023
Sites	1 location across France

Drugs / interventions tested

• Methylprednisolone (methylprednisolone) — full drug profile →
• Methylprednisolone placebo — full drug profile →

Conditions studied

• Persistent ARDS — all drugs for Persistent ARDS →

Sponsor

Assistance Publique Hopitaux De Marseille — full company profile →

Who can join

18 and older, any sex, with Persistent ARDS. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Unresolved ARDS is defined by the persistence of ARDS criteria at the end of the first week of evolution despite an appropriate treatment of the cause of ARDS. A persistent ARDS is associated with an increased mortality and prolonged lengths of mechanical ventilation, ICU stay and hospitalization. Persistent ARDS is characterized by ongoing inflammation, parenchymal-cell proliferation, and fibroproliferation leading to disordered deposition of collagen. All of these pathways may be responsive to corticosteroid therapy.

Only two randomized controlled double-blinded trials assessed the use of corticosteroids for persistent ARDS. In 24 patients, Meduri et al. reported an improvement of lung function and survival (1). In 180 patients, Steinberg et al showed no effect of corticosteroids on survival (2). A lower risk of death was observed when corticosteroids were started before 14 days after the onset of ARDS (2).

Alveolar procollagen III is validated as a biomarker of active fibroproliferation. Alveolar procollagen III \> 9 µg/L is associated to fibroproliferation (3).

As mortality was lower in patients who received corticosteroids while presenting a high alveolar level of procollagen III on inclusion, Steinberg et al. showed that patients presenting with a low level of procollagen III and treated with corticosteroids had an increased risk of death (2).

Investigatores hypothesize that the use of procollagen III could improve personalized decision-making regarding steroid treatment in patients presenting with persistent ARDS. The future of anti-fibrotic treatment, including corticosteroids, in persistent ARDS might propose to individualize the therapy according to the presence of an active fibroproliferative phase (precision or personalized medicine).

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Pharmacological agents for adults with acute respiratory distress syndrome.
   Lewis SR, Pritchard MW, Thomas CM, Smith AF. · · 2019 · cited 128× · PMID 31334568 · DOI 10.1002/14651858.cd004477.pub3
2. Biomarkers in acute respiratory distress syndrome.
   Jabaudon M, Blondonnet R, Ware LB. · · 2021 · cited 35× · PMID 33278123 · DOI 10.1097/mcc.0000000000000786
3. Chest CT scan and alveolar procollagen III to predict lung fibroproliferation in acute respiratory distress syndrome.
   Hamon A, Scemama U, Bourenne J, Daviet F, et al · · 2019 · cited 19× · PMID 30919111 · DOI 10.1186/s13613-019-0516-9