Treatment of SARS-CoV-2 Virus Disease (COVID-19) in Humans With Hemopurifier® Device

This is an Early Feasibility Study (EFS) investigating the use of the Hemopurifier® in the treatment of SARS-CoV-2 Virus Disease (COVID-19).

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Device: Hemopurifier

Detailed Description

Up to 40 ICU patients with severe or critical illness due to confirmed COVID-19 infection will be enrolled in up to 20 investigational sites. Patients will receive a four to six-hour treatment with the Hemopurifier® extracorporeal therapy daily for up to four days until discontinued because of clinical improvement or deterioration or upon the decision of the Principal Investigator. The patients will be monitored closely with vital signs and for hemodynamic stability. Patients will be followed for adverse events and device deficiencies. Blood work will be obtained.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92618
      • Hoag Hospital - Irvine
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
    • Sacramento, California, United States, 95817
      • UC Davis Health System
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Sciences Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Harlingen, Texas, United States, 78550
      • Valley Baptist Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Laboratory diagnosis of COVID-19 infection with any of the following disease characteristics:

   i. Early acute lung injury (ALI)/early acute respiratory distress syndrome (ARDS) ii. Severe disease, defined as:

   • dyspnea,
   • respiratory frequency ≥ 30/min,
   • blood oxygen saturation ≤ 93%,,
   • partial pressure of arterial oxygen to fraction of inspired oxygen ratio of <300 and/or

   • lung infiltrates >50% within 24 to 48 hours; iii. Life-threatening disease, defined as:

     1. respiratory failure,
     2. septic shock, and/or
     3. multiple organ dysfunction or failure.
2. Admission to the ICU or area of the hospital repurposed to function as an ICU for surge capacity management
3. Subject has maintained a MAP of > or = 65 without an increased dose of vasopressors for at least 2 hours and has clinical evidence of adequate volume status per investigative site criteria
4. Informed consent from the patient or legally authorized representative
5. Age > 18

Exclusion Criteria:

1. Stroke (known or suspected) within the last 3 months.
2. Severe congestive heart failure (NYHA III and IV classes).
3. Biopsy proven cancer not in remission.
4. Acute (an international normalized ratio (INR) of greater than 1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting cirrhosis and with an illness of less than 26weeks' duration or chronic (Child Pugh C) liver disease.
5. Known pre-existing non-COVID-19 related hypercoagulability or other coagulopathy
6. Terminal illness with a life expectancy of < 28 days or for whom a decision of withdrawal of care is in place or imminently anticipated or patients who have received prior extracorporeal therapy and had persistent, unstable hypotension.
7. Patients with known hypersensitivity to any component of the Hemopurifier.
8. Advance directive indicating to withhold life-sustaining treatment (except Cardiopulmonary Resuscitation).

9. Contraindications to extracorporeal blood purification therapy such as:

   i. Clinically relevant bleeding disorder, ii. Contraindication to anti-coagulation, iii. Pregnancy, iv. Inability to establish functional vascular access, v. Participation in another competing investigational drug, device or vaccine trial vi. Administration of an angiotensin converting enzyme (ACE) inhibitor in the previous 14 days. vii. Platelet count < 50,000 cells/microliter

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hemopurifier®; The Hemopurifier® will be placed within the extracorporeal circuit, all connections secured, treatment will utilize a blood pump at a flow rate of up to 200mL/min. The patients will be monitored for adverse events, device deficiencies and the development of hemodynamic instability. The treatment session will be for 4-6 hours once daily for 4 consecutive days.	Device: Hemopurifier; Hemopurifier treatments will be one four to six hour treatment session daily for up to 4 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment emergent adverse events	Safety and tolerability	Day 1 (Date of Consent) to Day 28
Incidence of device related adverse events	Safety and tolerability with adverse event graded at 2 or higher	Day 1 (Date of Consent) to Day 14
Incidence of serious adverse events	Safety and tolerability	Day 1 (Date of Consent) to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length if Stay in ICU	Length of ICU stay in days	Day 1 (Date of Consent) to Day 28
In-hospital mortality	Number of deaths during hospitalization	Day 1 (Date of Consent) to Day 28
Days free of ventilatory dependency	Number of days without ventilatory support	Day 1 (Date of Consent) to Day 28
Vasopressor-free days	Number of days without vasopressor support	Day 1 (Date of Consent) to Day 28
Sequential Organ Failure Assessment (SOFA)	SOFA scoring system predicts the clinical outcome of critically ill patients.	Before first daily filter treatment and after the last daily filter treatment (i.e. 4 days or more)
Acute Physiology and Chronic Health Evaluation (APACHE)	Measures the severity of disease for adult patients admitted to an ICU	Before first daily filter treatment and after the last daily filter treatment (i.e. 4 days or more)
SARS CoV-2 RNA levels in plasma and nasopharyngeal samples	Measures viral exposure and levels of circulating virus	Before each filter treatment, every 2 hours during filter treatment and immediately after filter discontinued
Total lymphocyte count	Measurement of lymphocytes as there seems to be a correlation with the disease severity and lymphopenia.	Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more)
C-reactive protein (CRP), IL-1, IL-6, and TNF alpha Tests	Measurement of inflammatory marker levels play a role in systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complication.	Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more)
D-dimer	Measurement of D-dimer levels as levels are elevated in patients with COVID-19 and correlate with disease severity, are a reliable prognostic marker for in-hospital mortality.	Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more)
Troponin-T	Measurement of Troponin-T as high levels of troponin is found in COVID-19 patients.	Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more)
Evaluation of SARS-CoV-2 RNA levels post-treatment Hemopurifier cartridges	Measures the levels of SARS-CoV-2 RNA captured in the filter	Until study completion, 1 week or for the duration of ICU admission
Evaluation of viral particle load post-treatment Hemopurifier cartridges	Measures the levels of viral particles captured in the filter	Until study completion, 1 week or for the duration of ICU admission

Collaborators and Investigators

• Sponsor: Aethlon Medical Inc.
• Investigators: Study Director: Steven LaRosa, MD, Aethlon Medical Inc.

Publications and helpful links

General Publications

• Amundson DE, Shah US, de Necochea-Campion R, Jacobs M, LaRosa SP, Fisher CJ Jr. Removal of COVID-19 Spike Protein, Whole Virus, Exosomes, and Exosomal MicroRNAs by the Hemopurifier(R) Lectin-Affinity Cartridge in Critically Ill Patients With COVID-19 Infection. Front Med (Lausanne). 2021 Oct 8;8:744141. doi: 10.3389/fmed.2021.744141. eCollection 2021.
• Gooldy M, Roux CM, LaRosa SP, Spaulding N, Fisher CJ Jr. Removal of clinically relevant SARS-CoV-2 variants by an affinity resin containing Galanthus nivalis agglutinin. PLoS One. 2022 Jul 28;17(7):e0272377. doi: 10.1371/journal.pone.0272377. eCollection 2022.

Helpful Links

• Website
• Website

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): November 14, 2022
• Study Completion (Actual): November 14, 2022

Study Registration Dates

• First Submitted: October 8, 2020
• First Submitted That Met QC Criteria: October 17, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; exosomes; plasmapheresis; Hemopurifier
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Virus Diseases
• Other Study ID Numbers: AEMD-2020-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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