Therapeutic Plasma Exchange for COVID-19-associated Hyperviscosity

NCT ID: NCT04441996

Last Updated: 2022-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-17
• Study Completion Date: 2021-03-18

Brief Summary

Many patients with Coronavirus Disease 2019 (COVID-19) have atypical blood clots. These blood clots can occur in either veins or arteries and be large, like in stroke or heart attack, or very tiny, called microthrombi. Some patients with COVID-19 even have blood clots despite being on anti-clotting medications. Blood with increased viscosity does not flow through the body normally, in the same way that syrup, a highly viscous liquid, and water, a minimally viscous liquid, flow differently. The researchers believe that hyperviscosity may contribute to blood clots and organ damage seen in patients with severe COVID-19. Plasma exchange removes a patient's plasma, which contains the large sticky factors that the researchers believe are increasing viscosity, and replaces it with plasma from healthy donors. In addition to providing important information about plasma exchange as a treatment in COVID-19 for patients, this study will provide data to justify resource and staffing decisions.

This study will enroll 20 participants who are critically ill from COVID-19. Participants will be randomized to receive therapeutic plasma exchange (TPE) or standard of care (SOC).

Detailed Description

Critically ill COVID-19 patients have high rates of complications, including respiratory failure, renal impairment, and a coagulopathic state that may exacerbate these conditions and contribute to additional end organ injury. Consistent with a fundamentally distinct nature of COVID-19-associated disease, our preliminary studies demonstrate that patients with COVID-19 exhibit an increase in plasma viscosity. Furthermore, the researchers have found that plasma viscosity strongly correlates with sequential organ failure assessment (SOFA) scores, a mortality prediction score used in the intensive care unit (ICU), in COVID-19 infected patients. These results strongly suggest that altered blood flow secondary to hyperviscosity may contribute to end organ injury and therefore morbidity and mortality in the most critically ill COVID-19 patients. More detailed analysis of the potential etiology of COVID-19-associated plasma hyperviscosity has demonstrated that these patients also have significantly elevated levels of the plasma protein fibrinogen. Increased fibrinogen levels, which may be either entirely responsible for or at least contribute to hyperviscosity in these patients, may be the primary mediator of refractory hypercoagulability in this patient population. Thus, hyperviscosity induced by hyperfibrinogenemia may be a critical driver of morbidity and mortality in patients with COVID-19.

Therapeutic plasma exchange (TPE) is the only procedure known to directly and rapidly decrease plasma viscosity, suggesting that TPE may improve patient outcomes in critically ill patients with COVID-19 by decreasing plasma viscosity and thereby enhancing blood flow. However, as a procedure, extensive implementation of TPE would require significant devotion of hospital resources, including apheresis machines and the staff needed to successfully conduct these procedures. The procedures alone require staff to have prolonged interactions with critically ill COVID-19 patients, placing them at a potentially increased risk for contracting COVID-19. It is therefore essential that clear and unequivocal data be generated in order to accurately assess the risk and benefits of this procedure for both patients and staff. Such data will also aid in determining the necessary resources that may be needed to successfully conduct TPE for this patient population.

Participants will be randomized in a 1:1 ratio to receive TPE or SOC. Participants in the TPE study arm will receive two treatments of TPE with frozen plasma on sequential days. Plasma viscosity will be measured before TPE (Day 1) and following the second TPE treatment (Day 3 or 4). Participants in the SOC study arm will also have their plasma viscosity assessed on Days 1 and 3. Participants will be followed for the duration of their hospital stay.

Conditions

COVID-19

Keywords

Hyperviscosity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Therapeutic plasma exchange (TPE)

Participants with COVID-19-associated hyperviscosity randomized to receive therapeutic plasma exchange (TPE).

Group Type: EXPERIMENTAL

Therapeutic plasma exchange (TPE)

Intervention Type: BIOLOGICAL

Participants will receive two treatments of TPE with frozen plasma (FP) replacement on two sequential days (Day 2 and Day 3). All procedures will be performed by the apheresis staff at the hospital sites, following institutional standard operating procedures. FP will be obtained from American Red Cross or LifeSouth Community Blood centers.

Standard of care

Participants with COVID-19-associated hyperviscosity randomized to receive standard of care treatment.

Group Type: ACTIVE_COMPARATOR

Standard of care

Intervention Type: OTHER

Participants will continue to receive standard of care and be closely monitored by ICU team for any change in clinical status, and any adverse events directly related to study intervention will be reported to the study investigator.

Interventions

Therapeutic plasma exchange (TPE)

Participants will receive two treatments of TPE with frozen plasma (FP) replacement on two sequential days (Day 2 and Day 3). All procedures will be performed by the apheresis staff at the hospital sites, following institutional standard operating procedures. FP will be obtained from American Red Cross or LifeSouth Community Blood centers.

Intervention Type: BIOLOGICAL

Standard of care

Participants will continue to receive standard of care and be closely monitored by ICU team for any change in clinical status, and any adverse events directly related to study intervention will be reported to the study investigator.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• Patients admitted to the ICU at Emory University Hospital, Emory University Hospital Midtown, or Emory Saint Joseph's Hospital
• Evidence of COVID-19 infection documented by a laboratory test either by one of the following:

• A diagnostic test (e.g., nasopharyngeal swab, tracheal aspirate, other)
• Positive serological test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies
• Medical records from outside institution
• Plasma viscosity >2.3 and <3.5 centipoise (cp) or Fibrinogen >800 mg/dL

Exclusion Criteria

• Patients with plasma viscosity > 3.5 cp
• Moribund patients that the ICU clinical team expects to die within 24 hours
• Patients with any condition that, in the opinion of the clinical team or investigator, could increase the subject's risk by participating in the study or confound the outcome of the study
• Patients participating in another clinical trial that prohibits the use of TPE
• Pregnant women
• Prisoners

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Cheryl Maier

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cheryl Maier, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STUDY00000949

Identifier Type: -

Identifier Source: org_study_id