CACOLAC : Randomized Trial of Citrulline Administration in the Hospital Patient in Intensive Care for COVID-19 Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- SOFA
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
结局指标
主要结局
SOFA
时间窗: Day 8
SOFA score for organ failures on D8 or last known SOFA score if the patient has died or been resuscitated
次要结局
- Plasma cytokines / chemokines(Days 1, 8 and 14)
- HLA-DR(Days 1, 8 and 14)
- SOFA(Days 3, 7, 10 and 14)
- Duration of mechanical ventilation(Day 28)
- Mortality in intensive care on day 28(Day 28)
- Measurement of the presence of SARS-CoV2(Days 1, 8 and 14)
- Number of days of exposure to each antibiotic per 1000 days of hospitalization(Day 28)
- Number and phenotype of lymphocytes(Days 1, 8 and 14)
- Number of Myeloid-derived suppressor cells(Days 1, 8 and 14)
- Repertoire T(Days 1, 3, 8, 10 and 14)
- Duration of hospital stay in hospital(Day 28)
- Nosocomial infections(D28)
- Mitochondrial activity(Days 1, 8 and 14)
- Plasma amino acids(Days 1, 8 and 14)
- Duration of hospitalization in intensive care(Day 28)
- Hospital mortality on day 28(Day 28)
- Lymphocyte T exhaustion(Days 1, 8 and 14)