Clinical trial NCT04990830: Effects of Low Molecular Weight Heparin Therapy With Soft-Mist Inhaler for COVID-19 Induced Hypoxemia
Official title: Early Effects of Low Molecular Weight Heparin Therapy With Soft-Mist Inhaler for COVID-19 Induced Hypoxemia: A Phase IIb Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID-19 Acute Respiratory Distress Syndrome
Hypoxemia
Keywords: Heparin
Low Molecular Weight Heparin
Inhalation
Antiviral
Soft Mist Inhaler
Lead sponsor: Istanbul University
Sponsor class: OTHER
First posted: 2021-08-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Treatment Group - Control Group
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in clinical status on a 5-point clinical scale for hypoxemia
timeFrame: Days 1-10
Secondary outcomes:
measure: Improvement rate of the breathing status
timeFrame: Day 1 and Day 10
measure: Change in peripheral oxygen saturation (Sp02)
timeFrame: Days 1-10
measure: Length of stay
timeFrame: Days 1-10
measure: Overall survival
timeFrame: Days 1-10
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Istanbul University Medical Faculty
state: Fatih
Study officials:
affiliation: Istanbul University Faculty of Pharmacy
name: Ayca Yildiz-Pekoz, PhD
role: STUDY_CHAIR
affiliation: Istanbul University Faculty of Medicine
name: Mustafa Erelel, MD
role: STUDY_DIRECTOR
References: