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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypoxemia; COVID-19 Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Inhaled Low molecular weight heparin; Drug: Standard Treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Turkey
  • Fatih
    • Istanbul, Fatih, Turkey, 34093
      • Istanbul University Medical Faculty

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inhalation Treatment; 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; Application with Soft Mist Inhaler; Other Names: Enoxaparin Sodium
Other: Control Group; Treatment: Standard COVID-19 treatment	Drug: Standard Treatment; Control Group

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Istanbul University
• Investigators: Study Chair: Ayca Yildiz-Pekoz, PhD, Istanbul University Faculty of Pharmacy; Study Director: Mustafa Erelel, MD, Istanbul University Faculty of Medicine

Publications and helpful links

Helpful Links

• Republic of Turkey Ministry of Health website on COVID-19

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2021
• Primary Completion (Actual): April 21, 2021
• Study Completion (Actual): May 21, 2021

Study Registration Dates

• First Submitted: July 29, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 5, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Inhalation; Heparin; Antiviral; Low Molecular Weight Heparin; Soft Mist Inhaler
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Signs and Symptoms, Respiratory; Lung Injury; Infant, Premature, Diseases; COVID-19; Hypoxia; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Enoxaparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Enoxaparin sodium
• Other Study ID Numbers: E-66175679-514.03.01-328141; 46325 (Other Identifier: Istanbul University Medical Faculty)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data sharing will be decided on a later date depending on completion of further study Phases

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No