Pyridostigmine in Severe SARS-CoV-2 Infection
Клучни зборови
Апстракт
Опис
The study will be divided into two phases, each with different variables to evaluate, as described below:
The primary objective of the first phase (proof-of-concept) will be to evaluate the effect of pyridostigmine on the serum level of interleukin (IL)-6 as an indicator of severe inflammation, as well as its kinetics throughout the days that the patient is hospitalized.
In the first phase, we will evaluate the safety and feasibility of the study in a representative sample and we will explore in a preliminary way the magnitude of the effect of the intervention. Safety will be evaluated according to the adverse effects reported in patients with acute intoxication (accidental or in suicide attempt) with pyridostigmine:
1. Abdominal pain/cramps
2. Diarrhea
3. Vomiting, nausea, or both
4. Hypersalivation
5. Urinary incontinence
6. Fasciculations or muscle weakness
7. Blurred vision
In the second phase (to be carried out only if the results of the first phase justify it), the primary outcome to be evaluated is mortality, the requirement of invasive or non-invasive mechanical ventilation, or an increase in the SOFA scale ≥2 points.
The following secondary outcomes were evaluated: changes in the total SOFA score between study entry and evaluation at 3, 7, and 14 days; the number of days of hospital stay, days of hospitalization in the intensive care unit, and the need (and if applicable, the number of days required) for invasive or non-invasive mechanical ventilation.
The variables to measure are sex, age at hospitalization, date of COVID-19 diagnosis, date and SOFA scale measurement, date of hospitalization, date of transfer to the intensive care unit, date of initiation of mechanical ventilation. , date and reason for leaving the intensive care unit.
Датуми
| Последен пат проверено: | 03/31/2020 |
| Прво доставено: | 04/08/2020 |
| Поднесено е проценето запишување: | 04/08/2020 |
| Прво објавено: | 04/13/2020 |
| Последното ажурирање е доставено: | 07/05/2020 |
| Последно ажурирање објавено: | 07/06/2020 |
| Крај на датумот на започнување на студијата: | 04/03/2020 |
| Проценет датум на примарно завршување: | 09/29/2020 |
| Проценет датум на завршување на студијата: | 04/29/2021 |
Состојба или болест
Интервенција / третман
Drug: Pyridostigmine
Drug: Placebo
Фаза
Групи за раце
| Рака | Интервенција / третман |
|---|---|
| Active Comparator: Pyridostigmine Pyridostigmine bromide tablet (60mg P.O. once per day for 14 days) | Drug: Pyridostigmine One 60mg tablet P.O. once per day for 14 days |
| Placebo Comparator: Placebo Placebo tablet (60mg P.O. once per day for 14 days) | Drug: Placebo One tablet P.O. once per day for 14 days |
Критериуми за подобност
| Возраст подобни за студии | 18 Years До 18 Years |
| Полови квалификувани за студии | All |
| Прифаќа здрави волонтери | Да |
| Критериуми | Inclusion Criteria: 1. Adult patients (≥18 years old) 2. Signed informed consent by the patient or designated legal representative 3. Confirmatory laboratory test for SARS-CoV-2 / COVID-19 infection 4. Pneumonia confirmed by imaging studies 5. Agree to venous blood collection according to the protocol 6. Need for hospitalization with increased mortality criteria according to published observations, including one or more of the following severity criteria according to the treating medical team: - a. Dyspnoea - b. Lung infiltrates> 50% of lung fields by CT - c. A ratio of partial pressure arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) <300 mmHg - d. Pulse oximetry <90% to ambient air, or a 3% drop in baseline oximetry, or need to increase supplemental oxygen due to chronic hypoxia, as well as the need for supplemental oxygen according to medical judgment And, alteration of one or more of the following laboratory studies at the time of hospital admission: - i. D-dimer >1 ug/mL - ii. Ferritin level >300 ng/mL - iii. C-reactive protein (CRP) >3mg/L - iv. Lactate dehydrogenase (LDH) >245 U/L - v. Lymphopenia <800 cells/uL - vi. Creatine kinase (CK) level >800 IU/L Exclusion Criteria: 1. Pyridostigmine allergy 2. If female, pregnancy or breastfeeding 3. Meet the following critical illness criteria before signing informed consent and taking the first dose of study medication: 1. . Need for mechanical ventilation 2. . Admission to the ICU for any reason 3. . Meet criteria for sepsis or septic shock 4. Concomitant autoimmune diseases 5. Known immunodeficiency (including HIV infection) 6. Need for mechanical ventilation before signing informed consent and taking the first dose of study medication 7. Inability to administer orally / enterally 8. Use of immunosuppressants or immuno-modulators in the preceding 28 days, including chemotherapeutics and steroids, unless recommended by the treatment medical team as part of the therapeutic approach for SARS-CoV-2 infection 9. Participation in interventional clinical trials in the preceding 28 days (however, participation in observational trials or those with no therapeutic intervention, is allowed) |
Исход
Мерки на примарниот исход
1. Critical condition or death [28 days]
2. IL-6 [14 days in-hospital, hospital discharge, or death]
