Procollagen-3 Driven Corticosteroids for Persistent Acute Respiratory Distress Syndrome

NCT03371498 | Terminated Phase 3 DMC

• 2 other identifiers: 2017-002867-162017-42
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Persistent ARDS

Outcome Measures

Primary Outcomes (1)

• Ventilator Free Days

  Number of Ventilator Free Days to day 60

  60 days

Secondary Outcomes (1)

• ICU and hospital mortality

  90 days

Study Arms (2)

Methylprednisolone Group

EXPERIMENTAL

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

Drug: Methylprednisolone

Control Group

PLACEBO COMPARATOR

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

Drug: Methylprednisolone placebo

Interventions

Methylprednisolone DRUG

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

Methylprednisolone Group

Methylprednisolone placebo DRUG

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

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Hôpitaux de Marseille

Marseille, 13354, France

Location

MeSH Terms

Interventions

Methylprednisolone

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jean-Olivier ARNAUD

  Assistance Publique Hôpitaux de Marseille

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 13, 2017
• Study Start: December 27, 2018
• Primary Completion: November 29, 2023
• Study Completion: November 29, 2023
• Last Updated: January 3, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)