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TerminatedNCT03371498ProCoCoUpdated Jan 3, 2024

Procollagen-3 Driven Corticosteroids for Persistent Acute Respiratory Distress Syndrome

A Phase 3 interventional study of Methylprednisolone and Methylprednisolone placebo in Persistent ARDS, sponsored by Assistance Publique Hopitaux De Marseille. Terminated at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-01-03.

Sponsored by Assistance Publique Hopitaux De Marseille · Phase 3, Interventional, and Treatment

Why this study was terminated
Insufficient recruitment of eligible patients.
Phase
Phase 3
Study type
Interventional
Enrollment
21
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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).

02

Conditions studied

03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age >= 18 years
  • Continuous endotracheal ventilation
  • Moderate - severe ARDS according to Berlin definition with PaO2/FiO2 ≤ 200 with PEEP >= 5 cm H2O
  • Date of ARDS onset : >= day 5 and ≤ day 14 after the onset of ARDS criteria (regardless of ARDS severity)
  • Procollagen III above 9 µg/L in a bronchoalveolar lavage performed by the attending physician between day 3 and day 13 after the onset of ARDS and realized within 5 days prior to randomization

Exclusion criteria

Exclusion Criteria:

  • Known pregnancy or breast feeding
  • Participation to another interventional trial within 30 days with mortality or ventilator free days as the main endpoint
  • Clinical evidence of active untreated infection
  • A known, undrained abscess
  • Intravascular nidus of infection
  • Disseminated fungal infection
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
21 participants (actual)

Study arms

  • Experimental
    Methylprednisolone Group

    Ventilated patients presenting moderate to severe ARDS with a procollagen III alveolar level above 9 µg/L will receive methylprednisolone

    Drug: Methylprednisolone

  • Placebo comparator
    Control Group

    Ventilated patients presenting moderate to severe ARDS with a procollagen III alveolar level above 9 µg/L will receive placebo

    Drug: Methylprednisolone placebo

Interventions

  • DrugMethylprednisolone

    Ventilated patients presenting moderate to severe ARDS with a procollagen III alveolar level above 9 µg/L

  • DrugMethylprednisolone placebo

    Ventilated patients presenting moderate to severe ARDS with a procollagen III alveolar level above 9 µg/L

05

What researchers measure

Primary outcomes

  1. Ventilator Free Days

    Number of Ventilator Free Days to day 60

    Time frame: 60 days

Secondary outcomes

  1. ICU and hospital mortality

    Number of death or alive patients on ICU discharge

    Time frame: 90 days

06

Study locations

1 site
  • Assistance Publique Hôpitaux de Marseille
    Marseille, 13354, France
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03371498
Lead sponsor
Assistance Publique Hopitaux De Marseille
Responsible party
Sponsor
First posted
Dec 13, 2017
Start date
Dec 27, 2018
Primary completion
Nov 29, 2023
Completion
Nov 29, 2023
Last update
Jan 3, 2024

Study contacts

Jean-Olivier ARNAUD
study director · Assistance Publique Hôpitaux de Marseille

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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