Biomarker-Guided Early Clarithromycin Treatment To Prevent Sepsis Progression In Community-Acquired Pneumonia: The REACT Randomized Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 330
- 试验地点
- 19
- 主要终点
- This is defined on day 4 and it is a composite endpoint of three conditions. Only patients meeting ALL three conditions will be considered as succeeding the primary endpoint.
研究概览
简要总结
The primary objective of the REACT RCT is to optimize the clinical benefit from adjunctive clarithromycin treatment shown in the ACCESS trial and to provide evidence for the clinical benefit of early start of adjunctive oral clarithromycin guided by suPAR to prevent the progression into sepsis in patients with CAP at risk.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Age equal to or above 18 years
- •Male or female gender
- •In case of women of reproductive age, willingness to use dual contraceptive method during the study period
- •Written informed consent provided by the patient. For subjects without decision-making capacity, informed consent must be obtained from a legally designated representative following the national legislation
- •Presence of at least two of the following signs: i) cough; ii) purulent sputum expectoration; iii) dyspnea; and/or iv) pleuritic chest pain
- •Community-acquired pneumonia (CAP)
- •PCT ≥0.25 ng/ml
- •suPAR ≥6 ng/ml
排除标准
- •Age below 18 years
- •Known infection by the human immunodeficiency virus
- •Any chronic anti-cytokine treatment for more than two months
- •QTc interval at rest in the ECG ≥500 msec or history of know long QT syndrome
- •Medical history of allergy to macrolides
- •Concomitant oral intake of astemizole, cizapride, doperidone, pimozide, terfenadine, midazolam, ranolazine, ergot alkaloids (e.g. ergotamine and dihydroergotamine), lomitapide and colchicine; patients may be enrolled in the trial if they stop these drugs during trial participation.
- •Medical history of torsades de pointes arrhythmia
- •Concomitant intake of lovostatin or simvastatin; patients may be enrolled in the trial if they stop these drugs during trial participation.
- •Concomitant presence of end-stage liver failure and end-stage renal failure.
- •Severe hypokalemia or severe hypomagnesemia; a patient may be enrolled one any of these electrolyte disturbances are restored.
- •Any contradictions for macrolide uptake
- •Denial of written informed consent
- •Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study
- •Participation in any other interventional trial
- •Any stage IV malignancy
- •Any do not resuscitate decision
- •Patients necessitating non-invasive ventilation or mechanical ventilation
- •Hospitalization in Intensive Care Unit
- •Infection by SARS-CoV-2
- •Oral or IV intake of corticosteroids at a daily dose equal to or greater than 0.4 mg/kg prednisone for a period greater than the last 15 days
- •Intake of any macrolide for the current episode of CAP under study
结局指标
主要结局
This is defined on day 4 and it is a composite endpoint of three conditions. Only patients meeting ALL three conditions will be considered as succeeding the primary endpoint.
This is defined on day 4 and it is a composite endpoint of three conditions. Only patients meeting ALL three conditions will be considered as succeeding the primary endpoint.
Condition A RSS i.e. the sum of scoring for the symptoms of cough, dyspnea, purulent sputum expectoration and pleuritic chest pain on visit 4 is decreased by at least 50% from the baseline score of day 1 without the development of any new symptom
Condition A RSS i.e. the sum of scoring for the symptoms of cough, dyspnea, purulent sputum expectoration and pleuritic chest pain on visit 4 is decreased by at least 50% from the baseline score of day 1 without the development of any new symptom
Condition B SOFA score on visit 4 is decreased by at least 30% from the baseline SOFA score of day 1
Condition B SOFA score on visit 4 is decreased by at least 30% from the baseline SOFA score of day 1
Condition C Combination of: (Plasma PCT on visit 4 has decreased by at least 80% from baseline PCT on screening or it is below 0.25 ng/ml) AND ([plasma IL-10 on visit 4 has decreased by at least 25% from IL-10 of visit 1 or it is below the lower limit of detection] or [the IL-8 to IL-10 ratio of day 4 has decreased less than 15% from the IL- 8 to IL-10 ratio of visit 1]).
Condition C Combination of: (Plasma PCT on visit 4 has decreased by at least 80% from baseline PCT on screening or it is below 0.25 ng/ml) AND ([plasma IL-10 on visit 4 has decreased by at least 25% from IL-10 of visit 1 or it is below the lower limit of detection] or [the IL-8 to IL-10 ratio of day 4 has decreased less than 15% from the IL- 8 to IL-10 ratio of visit 1]).
It is explicitly stated that patients dying prior to day 4 are considered failing the primary endpoint.
It is explicitly stated that patients dying prior to day 4 are considered failing the primary endpoint.
次要结局
- Development of new organ dysfunctions until day 28
- Progression into sepsis
- Clinical success at the TOC visit; this is also analyzed separately for patients infected or colonized by clarithromycin-susceptible and clarithromycin-resistant S.pneumoniae
- Need for up-escalation of the SoC administered antibiotics. This is considered as the change of the baseline administered SoC antibiotics into more broad-spectrum antibiotics.
- Alive hospital discharge until day 28
- Achievement of more than 50% decrease of baseline SOFA score at EOT visit
- Score of improvement of CAP-associated immune dysregulation (see sections of Laboratory procedures) at the EOT visit
- Change of cytokine production by PBMCs: IL -6, IL-8, IL-10, TNFα on day 4 from visit 1.
- Association of 28-day mortality with the score of improvement of CAP-associated immune dysregulation
- Association of 90-day mortality with score of improvement of CAP- associated immune dysregulation
- Cost of hospital stay
- Comparison of 28-day mortality between screening failure patients due to SuPAR <6 ng/ml and/or PCT <0.25 ng/ml, and patients randomized to the placebo group
研究者
Clinical trial information desk
Scientific
Hellenic Institute For The Study Of Sepsis