CACOLAC : Citrulline Administration in the Hospital Patient in Intensive Care for COVID-19 Acute Respiratory Distress Syndrome

NCT04404426 | Completed

• 3 other identifiers: 35RC20_9815_CACOLACCPP 1288 HPS12020-A01189-30
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Respiratory involvement of SARS-CoV2 leads to acute respiratory distress syndrome (ARDS) and significant immunosuppression (lymphopenia) exposing patients to long ventilation duration and late mortality linked to the acquisition of nosocomial infections. Lymphopenia characteristic of severe forms of ARDS secondary to SARS-CoV2 infection may be linked to expansion of MDSCs and arginine depletion of lymphocytes. Severe forms of COVID-19 pneumonitis are marked by persistent ARDS with acquisition of nosocomial infections as well as by prolonged lymphocytic dysfunction associated with the emergence of MDSC. It has been found in intensive care patients hypoargininaemia, associated with the persistence of organ dysfunction (evaluated by the SOFA score), the occurrence of nosocomial infections and mortality. Also, it has been demonstrated that in these patients, the enteral administration of ARG was not deleterious and increased the synthesis of ornithine, suggesting a preferential use of ARG by the arginase route, without significant increase in argininaemia nor effect on immune functions. L-citrulline (CIT), an endogenous precursor of ARG, is an interesting alternative to increase the availability of ARG. Recent data demonstrate that the administration of CIT in intensive care is not deleterious and that it very significantly reduces mortality in an animal model of sepsis, corrects hypoargininemia, with convincing data on immunological parameters such as lymphopenia, which is associated with mortality, organ dysfunction and the occurrence of nosocomial infections. The availability of ARG directly impacts the mitochondrial metabolism of T lymphocytes and their function. The hypothesis is therefore that CIT supplementation is more effective than the administration of ARG to correct hypoargininaemia, decrease lymphocyte dysfunction, correct immunosuppression and organ dysfunction in septic patients admitted to intensive care. The main objective is to show that, in patients hospitalized in intensive care for ARDS secondary to COVID-19 pneumonia, the group of patients receiving L-citrulline for 7 days, compared to the group receiving placebo, has a score of organ failure decreased on D7 (evaluated by the SOFA score) or by the last known SOFA score if the patient has died or been resuscitated.

Conditions

ARDS Secondary to COVID-19 Pneumonia

Outcome Measures

Primary Outcomes (1)

• SOFA

  SOFA score for organ failures on D8 or last known SOFA score if the patient has died or been resuscitated

  Day 8

Secondary Outcomes (17)

• Number and phenotype of lymphocytes

  Days 1, 8 and 14

• HLA-DR

  Days 1, 8 and 14

• Number of Myeloid-derived suppressor cells

  Days 1, 8 and 14

• Plasma cytokines / chemokines

  Days 1, 8 and 14

• Repertoire T

  Days 1, 3, 8, 10 and 14

Study Arms (2)

L-citrulline

EXPERIMENTAL

Administration of citrulline enterally for 7 days

Dietary Supplement: L-citrulline

Placebo

PLACEBO COMPARATOR

Administration of placeboenterally for 7 days

Other: Placebo

Interventions

L-citrulline DIETARY_SUPPLEMENT

Administration of citrulline enterally for 7 days.

L-citrulline

Placebo OTHER

Administration of placebo (water) enterally for 7 days

Placebo

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to 18 years;
• Patients admitted for less than 48 hours in intensive care for ARDS under mechanical ventilation according to the Berlin criteria published in 2012 (JAMA);
• Origin of ARDS: COVID-19 pneumopathy confirmed by PCR (nasopharyngeal or tracheal sample);
• Life expectancy\> 2 days;
• Affiliated to a social security scheme;
• Consent signed by the patient, the relative or the legal representative (except emergency procedure).

You may not qualify if:

• Pregnancy or breastfeeding in progress;
• State of immunosuppression defined by at least one of these criteria: continuous administration of steroids at any dose for more than a month before hospitalization, steroids in high doses (\> 15 mg / kg / day of methylprednisolone or equivalent), radiotherapy or chemotherapy in the previous year, proven humoral or cellular deficiency;
• Contraindication to enteral nutrition (2016 SRLF recommendations: "Enteral nutrition probably should not be used upstream of a high-flow digestive fistula in the event of intestinal obstruction, small ischemia or digestive hemorrhage active (Strong chord) ").
• Ongoing immunosuppressive therapy such as chemotherapy, cyclophosphamide, high dose corticosteroid therapy (\> 15 mg / kg / day);
• Participation in intervention research on a drug, or intervention research that may impact the immune system.

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (1)

Rennes University Hospital

Rennes, Britanny, 35000, France

Location

MeSH Terms

Interventions

Citrulline

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, multicenter, placebo-controlled, randomized, double-blind, two-parallel study, specific enteral administration by citrulline in a subgroup of resuscitation patients admitted for ARDS secondary to COVID-19 pneumonia, at infectious risk nosocomial important because having biological stigmas of immunosuppression on admission and under invasive mechanical ventilation for a prolonged period.

Study Record Dates

• First Submitted: May 22, 2020
• First Posted: May 27, 2020
• Study Start: November 4, 2020
• Primary Completion: March 25, 2021
• Study Completion: May 28, 2021
• Last Updated: June 2, 2021

Record last verified: 2021-05

Locations

FR (1)