Cri Analog PG1 Effectiveness and Safety in Covid-19

Phase 2

Withdrawn

• Conditions: Covid19
• Interventions: Drug: Standard therapeutic protocol; Drug: Analogs, Prostaglandin E1

• Registration Number: NCT04536363
• Lead Sponsor: Alonso Vera Torres

Brief Summary

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

Detailed Description

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

Study Timeline

• Study First Submitted: 2020-08-29
• Study First Submitted QC: 2020-09-01
• Study First Posted: 2020-09-02
• Study Start: 2020-12-03
• Primary Completion: 2020-12-03
• Study Completion: 2020-12-03
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-13
• Last Update Posted: 2023-09-15

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard therapeutic protocol	Standard therapeutic protocol	1. Dexamethasone (4mg ampoule, intravenous) 2. Tocilizumab (8 mg / kg (maximum dose 800 mg) IV, maximum 3) 3. Empirical Antibiotic Therapy in patients with suspected pneumonia (according to management guidelines) 4. Enoxaparin (40mg prefilled syringe) 5. Enoxaparin (20mg, 40mg, 60mg, 80mg prefilled syringe) 6. Low molecular weight heparin (5000IU prefilled syringe)
Standard Therapeutic Protocol + PGE1 Analog	Standard therapeutic protocol	Analog of PGE1 + Standard therapeutic protocol Standard medical treatment: 1. Dexamethasone (4mg ampoule, intravenous) 2. Tocilizumab (8 mg / kg (maximum dose 800 mg) IV, maximum 3) 3. Empirical Antibiotic Therapy in patients with suspected pneumonia (according to management guidelines) 4. Enoxaparin (40mg prefilled syringe) 5. Enoxaparin (20mg, 40mg, 60mg, 80mg prefilled syringe) 6. Low molecular weight heparin (5000IU prefilled syringe)
Standard Therapeutic Protocol + PGE1 Analog	Analogs, Prostaglandin E1	Analog of PGE1 + Standard therapeutic protocol Standard medical treatment: 1. Dexamethasone (4mg ampoule, intravenous) 2. Tocilizumab (8 mg / kg (maximum dose 800 mg) IV, maximum 3) 3. Empirical Antibiotic Therapy in patients with suspected pneumonia (according to management guidelines) 4. Enoxaparin (40mg prefilled syringe) 5. Enoxaparin (20mg, 40mg, 60mg, 80mg prefilled syringe) 6. Low molecular weight heparin (5000IU prefilled syringe)

Primary Outcome Measures

Name	Time	Method
Mortality	6 month	Death during or at the end of the intervention

Secondary Outcome Measures

Name	Time	Method
ICU stay	6 month	Specify number of days of ICU stay
Hypoxemia Resolution	6 month	Sat O2\> 90% to the environment
Days with high flow oxygen	6 month	Record days that the patient has received oxygen through a high flow system
Days of invasive mechanical ventilation prior to administration of PGE1 ANALOG	6 month	Number of days during which the patient was under invasive or non-invasive mechanical ventilation prior to the administration of PGE1 ANALOG
Evolution time of the disease	6 month	Time from the onset of symptoms to the day of admission
Days from admission to intensive care unit and administration of ANALOG PGE1	6 month	Number of days from admission to intensive care unit until administration of ANALOG PGE1