Platelet Inhibition With GP IIb/IIIa Inhibitor in Critically Ill Patients With Coronavirus Disease 2019 (COVID-19). A Compassionate Use Protocol
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- P/F ratio
研究概览
简要总结
This is a compassionate use, proof of concept, phase IIb, prospective, interventional, pilot study in which the investigators will evaluate the effects of compassionate-use treatment with IV tirofiban 25 mcg/kg, associated with acetylsalicylic acid IV, clopidogrel PO and fondaparinux 2.5 mg s/c, in patients affected by severe respiratory failure in Covid-19 associated pneumonia who underwent treatment with continuous positive airway pressure (CPAP).
详细描述
It is a investigator-initiated, compassionate use, prospective, phase 2b, non randomized, open-label, proof of concept study in which the investigators will evaluate the effects of compassionate-use treatment with IV tirofiban, associated with acetylsalicylic acid PO, clopidogrel PO and fondaparinux 2.5 mg s/c, in patients affected by severe respiratory failure in Covid-19 associated pneumonia who underwent treatment with continuous positive airway pressure (CPAP).
Patients will be treated with:
- 25 microgram per kilogram of body weight tirofiban as bolus IV injection (3 minutes) followed by continuous infusion at a rate of 0,15 microgram/kg/minute for 48 hours.
- acetylsalicylic acid 250 mg IV before starting tirofiban, and this will be continued at a dose of 75mg daily for 30 days.
- a loading dose of clopidogrel 300 mg PO, followed by 75mg daily for 30 days
- concurrent fondaparinux 2.5 mg s/c per day for the duration of the in hospital stay.
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Demographics, body mass index, comorbidities, SOFA score, APACHE II score, Glasgow Coma Scale will be assessed the day the patient is admitted to the IRCU.
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Blood gas analysis parameters (PaO2, PaCO2, HCO3-, lactates, SaO2, pH), Alveolar-arterial gradient, P/F ratio, respiratory rate, arterial blood pressure, heart rate and Chest X ray or Chest CT scan will be collected at admittance following the standard operating procedures of the IRCU for COVID-19 patients. The same measurement as detailed in 2) will be repeated 1 hour before and 1, 24, 48 and 168 hours after the loading bolus of tirofiban.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Laboratory-confirmed SARS-CoV-2-related pneumonia, defined as positive nasal swab for SARS-CoV-2 infection or positive IgM serum title. A laboratory confirmed diagnosis must be associated with a clinically confirmed COVID-19 pneumonia, with a history of fever ≥ 3 days and multiple pulmonary infiltrates at the chest X-Ray
- •Acute de novo severe hypoxic respiratory failure, defined by means of arterial blood gas analysis performed in room air showing severe hypoxemia with an arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio < 250 (according to the Berlin 2012 acute respiratory distress syndrome - ARDS - definition), requiring CPAP respiratory support
- •D-Dimer value ≥ 3 times the upper level of normal of the laboratory
排除标准
- •Ongoing bleeding or bleeding diathesis, contraindications for anticoagulation or increased bleeding risk or history of bleeding in the last eight weeks
- •Previous stroke or transient ischemic attack or any intracranial pathology in the last six months, major surgery or trauma within the previous six weeks
- •Laboratory confirmed Laboratory confirmed Glucose 6-Phosphate Dehydrogenase (G6PDH) deficiency.
- •Confirmed or suspected pregnancy or patients in childbearing age.
- •Previous known adverse effects or intolerance to the study drugs
- •Ongoing septic shock. Septic shock will be defined as the concomitant presence of sepsis (life-threatening organ dysfunction caused by a dysregulated host response to infection with a Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more) and need for vasopressors to maintain a mean arterial pressure of 65 mm Hg or greater and a serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia.
- •Need for surgery during hospitalization
- •Elevated risk of in hospital fall
- •Glasgow Coma Scale <15
- •Confirmed diagnosis of dementia or mental disability that jeopardizes the comprehension of the study protocol
- •Inability to sign the informed consent
研究组 & 干预措施
Tirofiban
- Patients will receive 25 microgram per kilogram of body weight tirofiban as bolus IV injection (3 minutes) followed by continuous infusion at a rate of 0.15 microgram/kg/minute for 48 hours.
- Patients will receive acetylsalicylic acid 250 mg IV before starting tirofiban, and this will be continued at a dose of 75 mg daily for 30 days.
- Patients will receive a loading dose of clopidogrel 300 mg PO, followed by 75 mg daily for 30 days
- Patents will receive concurrent fondaparinux 2.5 mg s/c per day for the duration of the hospital stay
干预措施: Tirofiban Injection (Drug)
Tirofiban
- Patients will receive 25 microgram per kilogram of body weight tirofiban as bolus IV injection (3 minutes) followed by continuous infusion at a rate of 0.15 microgram/kg/minute for 48 hours.
- Patients will receive acetylsalicylic acid 250 mg IV before starting tirofiban, and this will be continued at a dose of 75 mg daily for 30 days.
- Patients will receive a loading dose of clopidogrel 300 mg PO, followed by 75 mg daily for 30 days
- Patents will receive concurrent fondaparinux 2.5 mg s/c per day for the duration of the hospital stay
干预措施: Clopidogrel (Drug)
Tirofiban
- Patients will receive 25 microgram per kilogram of body weight tirofiban as bolus IV injection (3 minutes) followed by continuous infusion at a rate of 0.15 microgram/kg/minute for 48 hours.
- Patients will receive acetylsalicylic acid 250 mg IV before starting tirofiban, and this will be continued at a dose of 75 mg daily for 30 days.
- Patients will receive a loading dose of clopidogrel 300 mg PO, followed by 75 mg daily for 30 days
- Patents will receive concurrent fondaparinux 2.5 mg s/c per day for the duration of the hospital stay
干预措施: Acetylsalicylic acid (Drug)
Tirofiban
- Patients will receive 25 microgram per kilogram of body weight tirofiban as bolus IV injection (3 minutes) followed by continuous infusion at a rate of 0.15 microgram/kg/minute for 48 hours.
- Patients will receive acetylsalicylic acid 250 mg IV before starting tirofiban, and this will be continued at a dose of 75 mg daily for 30 days.
- Patients will receive a loading dose of clopidogrel 300 mg PO, followed by 75 mg daily for 30 days
- Patents will receive concurrent fondaparinux 2.5 mg s/c per day for the duration of the hospital stay
干预措施: Fondaparinux (Drug)
结局指标
主要结局
P/F ratio
时间窗: At baseline and 24, 48 and 168 hours after treatment initiation
Change in ratio between partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, and inspired oxygen fraction at baseline and after study treatment
PaO2 difference
时间窗: At baseline and 24, 48 and 168 hours after treatment initiation
Change in partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
A-a O2 difference
时间窗: At baseline and 24, 48 and 168 hours after treatment initiation
Change in alveolar-arterial gradient of oxygen at baseline and after study treatment. Arterial alveolar gradient will be calculated using the following parameters derived from arterial blood gas analysis: partial pressure of oxygen in arterial blood and partial pressure of carbon dioxide in arterial blood.
次要结局
- CPAP duration(From the first day of study drugs administration (T0) until day 7 post study drugs administration)
- In-hospital change in intensity of the respiratory support(At baseline and 72 and 168 hours after treatment initiation)
- PaCO2 difference(At baseline and 24, 48 and 168 hours after treatment initiation)
- HCO3- difference(At baseline and 24, 48 and 168 hours after treatment initiation)
- Lactate difference(At baseline and 24, 48 and 168 hours after treatment initiation)
- Hb difference(At baseline and 24, 48 and 168 hours after treatment initiation)
- Plt difference(At baseline and 24, 48 and 168 hours after treatment initiation)
- Adverse effects(From the first day of study drugs administration until day 30 post study drugs administration)
研究者
Pierachille Santus, MD, PhD
Professor of Respiratory Medicine
University of Milan