Effects of Low Molecular Weight Heparin Therapy With Soft-Mist Inhaler for COVID-19 Induced Hypoxemia

Study Overview
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Brief Summary
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This is an investigator initiated, single-center, open-label, Phase IIb clinical trial with 40 patients (for a total of 80 patients) to assess efficacy of Low molecular weight heparin using soft mist inhaler in the treatment of critically ill patients with COVID-19 (coronavirus disease of 2019) induced ARDS (acute respiratory distress syndrome). The patients will be assigned in a 1:1 ratio to receive standard treatment protocol plus inhaled Low molecular weight heparin. The primary objective is to determine the hypoxemia improvement on a 5-point clinical scale for COVID-19 induced ARDS patients.

Detailed Description
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Lungs are the major target organ of COVID-19, caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Multiple drug options have been evaluated for efficacy against worsening symptoms of COVID-19 patients. Low molecular weight heparin, known for its antiviral and anti-inflammatory effect, was determined to be applicable for ARDS-induced Hypoxemia. In cases of viral diseases that primarily targets the lungs, oral drugs and parenteral applications have shown to be insufficient due to low drug accumulation in the target organ site. An increase in drug dosage in order to achieve the necessary drug concentration leaves the patient with intolerable side effects. An inhalation delivery route of the drug would not only directly target the lungs but would also require less dosage. This is expected to increase patient tolerability and the efficacy of the treatment. Soft mist inhalers are advantageous above the other inhalation devices, for it reaches a higher retention rate in the lungs. Furthermore, the device to be used in this clinical study provides an enclosed system which decreases the risk of environmental contamination, thus is meant to protect healthcare professionals or to minimize associated contamination risks. This Phase-IIb clinical trial is to include 40 critically ill COVID-19 induced ARDS patients, that will receive Low molecular Weight Heparin via a soft mist inhaler at a dose of 4000 IU per administration, twice a day for 10 days in addition to the standard treatment determined by the Turkish Ministry of Health. A total of 80 patients will be enrolled, in which the drug receiving group will be assigned. The primary outcome of the clinical study is the improvement of ARDS induced hypoxemia on a 5-scale determination method at the end of the 10th day. The study inquires to perceive the early effects of inhaled Low molecular weight heparin on critically ill COVID-19 patients.

Official Title
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Early Effects of Low Molecular Weight Heparin Therapy With Soft-Mist Inhaler for COVID-19 Induced Hypoxemia: A Phase IIb Trial

Conditions
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Hypoxemia, COVID-19 Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Inhaled Low molecular weight heparin
* Drug: Standard Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive reserve transcriptase polymerase chain reaction (RT-PCR) test of nasopharyngeal swab for COVID- 19, and pneumonia confirmed by a Computed Tomography (CT). Negative reserve transcriptase polymerase chain reaction (RT-PCR) test of nasopharyngeal swab for COVID- 19, but radiological and biochemical examinations unambiguously suggest COVID-19, when other possible diagnoses were excluded. Exclusion Criteria: Pregnancy History of heparin and associated drug allergies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Treatment Group - Control Group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhalation Treatment<br>Treatment: Inhaled Low molecular weight heparin + Standard COVID-19 treatment, Inhaled Low molecular weight heparin (4000 IU given twice a day for 10 days) | Drug: Inhaled Low molecular weight heparin<br>* Application with Soft Mist Inhaler<br>* Other names: Enoxaparin Sodium;|
| Other: Control Group<br>Treatment: Standard COVID-19 treatment | Drug: Standard Treatment<br>* Control Group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clinical status on a 5-point clinical scale for hypoxemia | Level 1: if the patient can breathe comfortably in the room air. Level 2: if the peripheral oxygen saturation improves with an oxygen therapy up to 6 L/min via nasal cannula. Level 3: If it can be improved with a 500 mL reservoir oxygen mask with 15 L/min oxygen treatment. Level 4: If it can be improved with high flow oxygen therapy. Level 5: If the intubation is the only choice. | Days 1-10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement rate of the breathing status | Change in number of patients that were able to breath in room air will be compared on Day 1 and Day 10 (Comparison between the Treatment Group and Control Group) | Day 1 and Day 10 | 
| Change in peripheral oxygen saturation (Sp02) | A change in SpO2 levels in the duration of the study (SpO2 < % 95) | Days 1-10 | 
| Length of stay | Number of patients administered to intensive care unit (ICU) | Days 1-10 | 
| Overall survival | During or post-study follow up period | Days 1-10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heparin, Low Molecular Weight Heparin, Inhalation, Antiviral, Soft Mist Inhaler