The Clinical trial aim to evaluate the effectiveness and safety of the administration of the intravenous prostaglandin E1 analog in the reduction of mortality and complications of patients with COVID-19 diagnosis. Therefore the investigators propose an open randomized clinical trial in the Fundación Santa Fe de Bogota
COVID-19 is a public health problem that has spread throughout the world and has forced
different scientific societies to consider effective measures to control the increasing
spread of the disease. This disease is presumed to follow a virologic pattern similar to
SARS-CoV-1 (Severe acute respiratory syndrome coronavirus 1) . The disease spectrum includes
asymptomatic stage and pre-symptomatic , mild infection uncomplicated, mild and severe
pneumonia and the acute Respiratory distress syndrome (ARDS) constituting the point of no
return characterized by ventilatory mechanics preserved with severe refractory hypoxemia. The
pulmonary involvement of patients with COVID-19 causes an endothelial injury, which can be
associated with changes in vascular permeability, manifesting as thrombotic, venous and
arterial disease in patients with COVID-19. Alprostadil, a prostaglandin E1 analog that has a
vasodilator mechanism, inhibitory property of platelet aggregation and inducer of
bronchodilation, promises to prevent complications of SARS-CoV2. In addition to that
Alprostadil has been used in other clinical trials as treatment for the acute respiratory
distress syndrome caused by Influenza, in which it showed no harm or benefit, nonetheless the
pathophysiology of the acute distress respiratory syndrome caused by Influenza and COVID-19
are similar in macroscopic changes but very different in microscopic changes which is why it
is important to evaluate the effectiveness and safety of the administration of intravenous
prostaglandin E1 analog in the reduction of mortality and complications of patients with
COVID-19 diagnosis. Therefore the investigators propose an open randomized clinical trial,
where patients in the intensive care unit of the Fundación Santa Fe de Bogotá are randomized
into two groups, where one is going to be treated with standardized treatment after the
guidelines recommendations of the Colombian Infectology Society and the other one is going to
receive the same standardized treatment and Alprostadil infusion for a maximum of 7 days.
During the infusion of the Alprostadil the patient will be carefully monitored by the
intensive care unit team. After the Infusion the patient will be followed up for 30 days in
which the mortality and hypoxemia resolution will be monitored.
Key words: COVID-19, Prostaglandin E1 Analogue, Alprostadil, Mortality, Acute respiratory
distress syndrome
Drug: Analogs, Prostaglandin E1
Analog of PGE1:
Infusion starting dose: 0.05 -0.01 mcg per kilogram of weight per minute in infusion continues, maximum 7 days, until achieving the desired clinical response (increase in PaO2), at that time decrease the infusion rate to the lowest dose possible to keep answer. This can be accomplished by decreasing the dose from 0.1 to 0.05 to 0.025 to 0.01 mcg / kg / min.
If the response to 0.05 mcg / kg / min is inadequate, the dose can be increased to 0.4 mcg / kg / min, although in general high doses do not produce better effects. Maximum continuous infusion for up to 7 days
Drug: Standard therapeutic protocol
Standard medical treatment is governed by current recommendations of national scientific societies and the Ministry of Health and Social Protection and may be modified throughout the course of the study according to the available evidence. In addition, the criteria of the treating physician are taken into account.
Among the alternatives proposed by the current clinical practice guidelines are:
Dexamethasone (4mg ampoule, intravenous) Dose: 6mg intravenous every day for a maximum of 10 days
Tocilizumab Dose: 8 mg / kg (maximum dose of 800 mg) IV, maximum 3 doses 8 to 12 hours apart
Empirical Antibiotic Therapy in patients with suspected pneumonia (according to management guidelines)
Enoxaparin (40mg prefilled syringe) Dose: 40mg subcutaneously every 24 hours
Enoxaparin (20mg, 40mg, 60mg, 80mg prefilled syringe) Dose: 1mg / kg every 12 hours
Low molecular weight heparin (5000IU prefilled syringe) Dose: 5,000 IU subcutaneous every 12 hours
Inclusion Criteria:
- Patient older than 18 years of age
- COVID19 diagnosis:
- RT PCR for COVID-19 positive in respiratory tract sample (nasopharyngeal swab,
sputum, bronchoalveolar lavage)
- At least 2 of the following symptoms: cough, odynophagia, dyspnea, asthenia,
adynamia, gastrointestinal symptoms.
- Findings compatible with viral pneumonia on chest tomography or chest
radiography.
- Risk of respiratory deterioration given by at least 1 of the following:
- Hypoxemia: PaO2 <60 mmHg, SaO2 <90% or supplemental O2 requirement to maintain SaO2>
90%
- Call Score ≥ 9 points
- FR> 30 / min
- PaO2 / FiO2 less than 200
- Intubated patients without deterioration of other organs (without acute kidney injury,
without elevated transaminases).
- Progression of radiological findings of pneumonia.
- Patients with moderate or severe oxygenation disorder, with diaphragm of 200-100 and
<100 respectively, who require supplemental oxygen at high flow (non-rebreathing mask
or high flow cannula).
- Complete record of medical history, allergies, and medical conditions that preclude
the use of prostaglandin E1 analogs have been ruled out.
- Voluntary participation in the study, demonstrating fullness through informed consent.
Exclusion Criteria:
1. Allergy or sensitivity to PEG1 analog or components
2. Arterial hypotension defined as blood pressure less than 90/60 mm of mercury or mean
arterial pressure less than 65mm of mercury or BP requirement <80/50 mmHg or TAM 60
mmHg with norepinephrine requirement greater than 0.1 mcg / kg / min
3. Severe hypertension defined as systolic blood pressure greater than or equal to 180 mm
of mercury and / or diastolic blood pressure greater than or equal to 110 mm of
mercury
4. Bradycardia defined as heart rate less than 60 beats per minute
5. Previous events of priapism or penile anatomical changes
6. Sickle cell disease, multiple myeloma, leukemia, polycythemia vera, thrombocythemia
predisposing to priapism
7. Hemorrhagic diathesis
8. Active peptic ulcer, trauma, or recent brain hemorrhage.
9. Abnormal pulmonary venous return with obstruction
10. Pregnancy: A pregnancy test will be performed upon admission of the patient to the
study (if applicable).
11. Heart failure with NYHA functional class> 1
12. Hemodynamically relevant arrhythmia: That generates hypotension, chest pain,
dysfunction, sensory disturbance or other signs of low output
13. Mitral and / or aortic stenosis and / or insufficiency of either
14. Unstable angina
15. Acute Myocardial Infarction in the last 6 months
16. Ischemic or hemorrhagic cerebrovascular event in the last 6 months
17. Child B or C or decompensated liver cirrhosis
18. Chronic kidney disease in renal replacement therapy
19. Serious medical condition or laboratory findings that, in the investigator's judgment,
may compromise patient safety during participation in the study
Alonso Vera Torres, MD
+573107632766
Alonso.Vera@fsfb.org.co
Jose De la Hoz, MD
3507084846
jose.delahoz@fsfb.org.co