Clinical trial NCT04595903: Treatment of SARS-CoV-2 Virus Disease (COVID-19) in Humans With Hemopurifier® Device
Official title: Treatment of SARS-CoV-2 Virus Disease (COVID-19) in Humans With Hemopurifier® Device
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: COVID-19
Keywords: Hemopurifier
SARS-CoV-2
COVID-19
exosomes
plasmapheresis
Lead sponsor: Aethlon Medical Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-22
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This trial will evaluate the use of the Hemopurifier in patients with SARS-CoV-2 Virus Disease (COVID-19). The Hemopurifier is an extracorporeal device device that combines plasma filtration, size exclusion and affinity binding of mannosylated structures including enveloped viruses and exosomes. The study will evaluate whether the device is safe in COVID-19 patients along with clearing virus and improving outcomes in infected patients. Subjects 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 decision of the Principal Investigator.
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of treatment emergent adverse events
timeFrame: Day 1 (Date of Consent) to Day 28
measure: Incidence of device related adverse events
timeFrame: Day 1 (Date of Consent) to Day 14
measure: Incidence of serious adverse events
timeFrame: Day 1 (Date of Consent) to Day 28
Secondary outcomes:
measure: Length if Stay in ICU
timeFrame: Day 1 (Date of Consent) to Day 28
measure: In-hospital mortality
timeFrame: Day 1 (Date of Consent) to Day 28
measure: Days free of ventilatory dependency
timeFrame: Day 1 (Date of Consent) to Day 28
measure: Vasopressor-free days
timeFrame: Day 1 (Date of Consent) to Day 28
measure: Sequential Organ Failure Assessment (SOFA)
timeFrame: Before first daily filter treatment and after the last daily filter treatment (i.e. 4 days or more)
measure: Acute Physiology and Chronic Health Evaluation (APACHE)
timeFrame: Before first daily filter treatment and after the last daily filter treatment (i.e. 4 days or more)
measure: SARS CoV-2 RNA levels in plasma and nasopharyngeal samples
timeFrame: Before each filter treatment, every 2 hours during filter treatment and immediately after filter discontinued
measure: Total lymphocyte count
timeFrame: Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more)
measure: C-reactive protein (CRP), IL-1, IL-6, and TNF alpha Tests
timeFrame: Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more)
measure: D-dimer
timeFrame: Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more)
measure: Troponin-T
timeFrame: Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more)
measure: Evaluation of SARS-CoV-2 RNA levels post-treatment Hemopurifier cartridges
timeFrame: Until study completion, 1 week or for the duration of ICU admission
measure: Evaluation of viral particle load post-treatment Hemopurifier cartridges
timeFrame: Until study completion, 1 week or for the duration of ICU admission
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Hoag Hospital - Irvine
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Sacramento
country: United States
facility: UC Davis Health System
state: California
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Shreveport
country: United States
facility: LSU Health Sciences Center
state: Louisiana
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Harlingen
country: United States
facility: Valley Baptist Medical Center
state: Texas
Study officials:
affiliation: Aethlon Medical Inc.
name: Steven LaRosa, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.