Trial Outcomes & Findings for Therapeutic Plasma Exchange for COVID-19-associated Hyperviscosity (NCT NCT04441996)

NCT ID: NCT04441996

Last Updated: 2022-12-21

Results Overview

Plasma viscosity is measured in centipoise (cP). The normal range is 1.4 - 1.8 cP and measurements above this range indicate increased viscosity.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

20 participants

Primary outcome timeframe

Day 1 (within 24 hours prior to TPE), Day 4 (within 24 hours of last TPE)

Results posted on

2022-12-21

Participant Flow

Participants were recruited from Emory University Hospital, Emory University Hospital Midtown, and Emory Saint Joseph's Hospital in Atlanta, Georgia, USA. Participant enrollment began July 17, 2020 and all follow-up assessments were completed by March 18, 2021.

Participant milestones

Participant milestones
Measure
Therapeutic Plasma Exchange (TPE)
Participants with Coronavirus Disease 2019 (COVID-19) associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Overall Study
STARTED
10
10
Overall Study
COMPLETED
10
10
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Therapeutic Plasma Exchange for COVID-19-associated Hyperviscosity

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Total
n=20 Participants
Total of all reporting groups
Age, Continuous
58.9 years
STANDARD_DEVIATION 14.4 • n=5 Participants
58.8 years
STANDARD_DEVIATION 9.04 • n=7 Participants
58.9 years
STANDARD_DEVIATION 11.7 • n=5 Participants
Sex: Female, Male
Female
1 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
Sex: Female, Male
Male
9 Participants
n=5 Participants
7 Participants
n=7 Participants
16 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
5 Participants
n=5 Participants
7 Participants
n=7 Participants
12 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
4 Participants
n=5 Participants
3 Participants
n=7 Participants
7 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
7 Participants
n=5 Participants
5 Participants
n=7 Participants
12 Participants
n=5 Participants
Race (NIH/OMB)
White
2 Participants
n=5 Participants
3 Participants
n=7 Participants
5 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Region of Enrollment
United States
10 Participants
n=5 Participants
10 Participants
n=7 Participants
20 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (within 24 hours prior to TPE), Day 4 (within 24 hours of last TPE)

Plasma viscosity is measured in centipoise (cP). The normal range is 1.4 - 1.8 cP and measurements above this range indicate increased viscosity.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Plasma Viscosity
Baseline
2.35 cP
Standard Deviation 0.37
2.47 cP
Standard Deviation 0.34
Plasma Viscosity
Post-treatment
1.61 cP
Standard Deviation 0.09
2.47 cP
Standard Deviation 0.48

PRIMARY outcome

Timeframe: Up to Day 28

Population: This analysis includes participants in the TPE study arm.

The primary safety endpoint is assessed as the cumulative incidence of adverse events directly associated with TPE during the study period as determined by clinical judgment of ICU team providing direct patient care and the study PI.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Cumulative Incidence of Adverse Events
1 adverse events

SECONDARY outcome

Timeframe: Up to Day 28

The number of participants dying from any cause is reported as a cumulative measures of mortality.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Cumulative All Cause Mortality
Day 1 to Day 14
0 Participants
2 Participants
Cumulative All Cause Mortality
Day 1 to Day 21
1 Participants
4 Participants
Cumulative All Cause Mortality
Day 1 to Day 28
2 Participants
5 Participants
Cumulative All Cause Mortality
Day 1 to Day 3
0 Participants
0 Participants
Cumulative All Cause Mortality
Day 1 to Day 7
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Up to Day 28

The number of bleeding and thromboembolic complications will be compared between study arms. This endpoint is a composite outcome including any acute bleeding requiring transfusion support, venous thrombosis (deep vein thrombosis or pulmonary embolism), arterial clots (myocardial infarction, stroke, limb ischemia), renal replacement therapy or catheter line related clots. The values reported are cumulative.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Cumulative Count of Bleeding and Thromboembolic Complications
Day 1 to Day 3
0 Participants
0 Participants
Cumulative Count of Bleeding and Thromboembolic Complications
Day 1 to Day 7
1 Participants
0 Participants
Cumulative Count of Bleeding and Thromboembolic Complications
Day 1 to Day 14
1 Participants
0 Participants
Cumulative Count of Bleeding and Thromboembolic Complications
Day 1 to Day 21
2 Participants
2 Participants
Cumulative Count of Bleeding and Thromboembolic Complications
Day 1 to Day 28
2 Participants
2 Participants

SECONDARY outcome

Timeframe: Up to Day 28

Population: This analysis includes participants experiencing treatment failure.

Time to treatment failure will be assessed in days and is defined as plasma viscosity \> 3.5 cP and/or the participant is offered TPE outside of trial by primary clinical team.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=2 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=2 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Time to Treatment Failure
5.5 days
Standard Deviation 2.12
2.5 days
Standard Deviation 3.54

SECONDARY outcome

Timeframe: Up to Day 48

The number of days spent in the ICU after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose ICU stay ended due to death.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Duration of ICU Stay
23.1 days
Standard Deviation 15.7
16.0 days
Standard Deviation 11.4

SECONDARY outcome

Timeframe: Up to Day 48

The number of days spent hospitalized after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose hospitalization ended due to death.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Duration of Hospital Stay
27.2 days
Standard Deviation 12.4
21.7 days
Standard Deviation 12.0

SECONDARY outcome

Timeframe: Up to Day 48

The number of participants in each study arm discharged to home or to a long-term acute care (LTAC) hospital, versus palliative care or death.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Discharge Disposition
Home or LTAC
7 Participants
5 Participants
Discharge Disposition
Palliative care or death
3 Participants
5 Participants

SECONDARY outcome

Timeframe: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28

The clinical status of participants was assessed using a single item modified from the World Health Organization (WHO) ordinal clinical severity scale for COVID. The instrument was customized for this study to evaluate thrombotic/bleeding events. In this 12-point ordinal scale, a score of 1 indicates no evidence of infection and the severity of the clinical status increases as the number of necessary interventions increases to the final score of 12, which is death. All patients were included at every timepoint recorded, with "terminal" scores carried over from the measure before for those that expired or fully recovered.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Clinical Status Score
Day 4 (1 day after second TPE treatment)
7.0 score on a scale
Interval 6.0 to 7.0
8.0 score on a scale
Interval 7.25 to 8.0
Clinical Status Score
Day 1 (day of study enrollment)
7.0 score on a scale
Interval 6.0 to 7.75
8.0 score on a scale
Interval 7.25 to 8.0
Clinical Status Score
Day 7
7.0 score on a scale
Interval 6.0 to 8.0
8.0 score on a scale
Interval 7.0 to 8.0
Clinical Status Score
Day 14
8.0 score on a scale
Interval 6.0 to 8.0
7.5 score on a scale
Interval 7.0 to 9.75
Clinical Status Score
Day 21
7.5 score on a scale
Interval 5.5 to 8.0
8.0 score on a scale
Interval 7.0 to 12.0
Clinical Status Score
Day 28
7.0 score on a scale
Interval 5.5 to 8.75
10.0 score on a scale
Interval 7.0 to 12.0

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Body temperature was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Body temperature will be assessed in degrees Celsius.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Blood pressure was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Systolic blood pressure will be assessed in millimeters of mercury (mm Hg).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Blood pressure was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Diastolic blood pressure will be assessed in millimeters of mercury (mm Hg).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Heart rate was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Heart rate will be assessed as beats per minute.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Respiratory rate was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Respiratory rate will be assessed as breaths per minute.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Day 28

Population: This analysis includes participants who were on a ventilator; two participants in the TPE arm were never on a ventilator.

The number of days participants are on a ventilator, among participants who were ever on a ventilator after study enrollment.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=8 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Ventilator Days
22.6 days
Standard Deviation 11.6
19.2 days
Standard Deviation 11.2

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: FiO2 was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

The oxygen percent delivered with a ventilator that is needed to maintain blood oxygen levels will be compared between study arms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28

Population: This analysis includes participants who were assessed for PEEP at the indicated time point.

PEEP during ventilator use is measured in centimeters of water (cmH2O) and is the pressure in the lungs above atmospheric pressure, at the end of an exhalation. Higher PEEP (10 cmH2O or greater) may be associated with improved mortality, compared with PEEP below 10 cmH2O.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=5 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=7 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Positive End-Expiratory Pressure (PEEP)
Day 21
11.0 cmH2O
Standard Deviation 1.2
11.0 cmH2O
Standard Deviation 2.0
Positive End-Expiratory Pressure (PEEP)
Day 1 (day of study enrollment)
12.7 cmH2O
Standard Deviation 5.0
15.9 cmH2O
Standard Deviation 5.9
Positive End-Expiratory Pressure (PEEP)
Day 4 (one day after second TPE treatment)
11.6 cmH2O
Standard Deviation 4.3
13.0 cmH2O
Standard Deviation 3.7
Positive End-Expiratory Pressure (PEEP)
Day 7
13.0 cmH2O
Standard Deviation 6.2
11.3 cmH2O
Standard Deviation 3.9
Positive End-Expiratory Pressure (PEEP)
Day 14
13.0 cmH2O
Standard Deviation 2.0
13.3 cmH2O
Standard Deviation 2.7
Positive End-Expiratory Pressure (PEEP)
Day 28
11.0 cmH2O
Standard Deviation 2.6
12.7 cmH2O
Standard Deviation 7.0

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Vasopressor requirements were not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Whether or not breathing assistance from vasopressors is needed will be compared between study arms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Need for treatment from an RRT was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Whether or not breathing assistance from an RRT is needed will be compared between study arms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28

Population: This analysis includes participants who had a SOFA score assessment at the indicated time point.

The Sequential Organ Failure Assessment (SOFA) score is a method of predicting mortality that is based on the degree of dysfunction of six organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). Each organ system is scored between 0 and 4, where 0 indicates normal function and 4 indicates a high degree of dysfunction. Total scores range from 0 to 24. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Sequential Organ Failure Assessment (SOFA) Score
Day 14
12.5 score on a scale
Interval 8.75 to 13.75
12.5 score on a scale
Interval 11.0 to 15.0
Sequential Organ Failure Assessment (SOFA) Score
Day 1 (day of study enrollment)
10.5 score on a scale
Interval 8.5 to 12.75
13.0 score on a scale
Interval 11.25 to 14.0
Sequential Organ Failure Assessment (SOFA) Score
Day 4 (one day after second TPE treatment)
11.0 score on a scale
Interval 7.75 to 12.5
11.5 score on a scale
Interval 11.0 to 12.75
Sequential Organ Failure Assessment (SOFA) Score
Day 7
11.0 score on a scale
Interval 10.0 to 12.0
12.0 score on a scale
Interval 11.25 to 13.75
Sequential Organ Failure Assessment (SOFA) Score
Day 21
11.5 score on a scale
Interval 8.75 to 12.0
13.0 score on a scale
Interval 10.75 to 15.75
Sequential Organ Failure Assessment (SOFA) Score
Day 28
11.5 score on a scale
Interval 8.25 to 12.75
12.0 score on a scale
Interval 9.0 to 15.75

SECONDARY outcome

Timeframe: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28

Population: This analysis includes participants with available arterial blood gas (ABG) values.

The PaO2/FiO2 ratio is decreased with hypoxia. A value of less than 200 indicates acute respiratory distress syndrome (ARDS).

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=5 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=9 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio
Day 1 (day of study enrollment)
219 PaO2/FiO2 ratio
Standard Deviation 102
166 PaO2/FiO2 ratio
Standard Deviation 79
Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio
Day 4 (one day after second TPE treatment)
132 PaO2/FiO2 ratio
Standard Deviation 80
157 PaO2/FiO2 ratio
Standard Deviation 44
Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio
Day 7
151 PaO2/FiO2 ratio
Standard Deviation 131
141 PaO2/FiO2 ratio
Standard Deviation 54
Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio
Day 14
109 PaO2/FiO2 ratio
Standard Deviation 21
101 PaO2/FiO2 ratio
Standard Deviation 43
Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio
Day 21
104 PaO2/FiO2 ratio
Standard Deviation 32
145 PaO2/FiO2 ratio
Standard Deviation 2
Partial Pressure of Arterial Oxygen (PaO2)/Percentage of Inspired Oxygen (FiO2) Ratio
Day 28
108 PaO2/FiO2 ratio
Standard Deviation 54
146 PaO2/FiO2 ratio
Standard Deviation 127

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for calculating the ventilatory ratio was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Ventilatory ratio will be documented. The formula for the ventilatory is \[minute ventilation (ml/min) × PaCO2 (mm Hg)\]/(predicted body weight × 100 × 37.5).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The normal range for WBC is 3,400 to 6,600 cells per microliter (cells/mL) of blood. A high WBC occurs when inflammation or infection is present.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

Hemoglobin is measured in grams per deciliter (grams/dL). A normal Hb count for males is 13.2 to 16.6 grams/dL and a normal count for females is 11.6 to 15 grams/dL. A patient has anemia when their hemoglobin is low.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

A measure of hematocrit is the volume of red blood cells in the total blood volume. Normal hematocrit for males is 40 to 54% and a normal measurement for females is 36 to 48%

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

A normal platelet is 150,000 to 450,000 platelets per microliter of blood. An excess of platelets in the blood can be caused by inflammation or infection.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

MVP is a measurement of platelet size. Platelet size tends to be increased when platelet count is high. Typical platelet volume is 9.4 to 12.3 femtoliters (fL).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The normal range for BUN is 7 to 20 milligrams per deciliter (mg/dL) of blood. A high BUN value indicates that kidneys are not functioning well.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28

Population: This analysis includes participants who had creatinine assessed at the indicated time point.

The normal range for creatinine is 0.84 to 1.21 mg/dL of blood. High serum creatinine indicates that kidneys are not functioning well.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Creatinine
Day 1 (day of study enrollment)
2.5 mg/dL
Standard Deviation 2.1
2.9 mg/dL
Standard Deviation 1.8
Creatinine
Day 4 (one day after second TPE treatment)
2.0 mg/dL
Standard Deviation 1.3
2.6 mg/dL
Standard Deviation 1.7
Creatinine
Day 1
2.3 mg/dL
Standard Deviation 1.4
2.6 mg/dL
Standard Deviation 1.7
Creatinine
Day 14
2.6 mg/dL
Standard Deviation 2.3
2.7 mg/dL
Standard Deviation 1.8
Creatinine
Day 21
2.3 mg/dL
Standard Deviation 3.3
2.8 mg/dL
Standard Deviation 1.7
Creatinine
Day 28
1.3 mg/dL
Standard Deviation 1.6
2.0 mg/dL
Standard Deviation 1.6

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

For adults, normal values for total bilirubin are around 1.2 mg/dL of blood. High bilirubin indicates that the liver is not functioning well.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The normal range for total protein is 6.0 to 8.3 g/dL of blood. High levels of total protein can occur with inflammation or infection while low levels may indicate kidney or liver problems, or malnutrition.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The normal range for albumin is 3.4 to 5.4 g/dL of blood. High albumin may indicate acute infection while low albumin can indicate malnutrition or liver disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28

Population: This analysis includes participants who had CRP assessed at the indicated time point.

A normal value for CRP (with a standard test) is less than 10 milligrams per liter (mg/L) of blood. CRP increases with inflammation, which could be attributed to an infection, chronic inflammatory disease or heart disease.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
C-reactive Protein (CRP)
Day 1 (day of study enrollment)
226 mg/L
Standard Deviation 74
234 mg/L
Standard Deviation 115
C-reactive Protein (CRP)
Day 4 (one day after second TPE treatment)
83 mg/L
Standard Deviation 37
179 mg/L
Standard Deviation 115
C-reactive Protein (CRP)
Day 7
153 mg/L
Standard Deviation 153
210 mg/L
Standard Deviation 91
C-reactive Protein (CRP)
Day 14
119 mg/L
Standard Deviation 94
195 mg/L
Standard Deviation 81
C-reactive Protein (CRP)
Day 21
149 mg/L
Standard Deviation 134
71 mg/L
Standard Deviation 27
C-reactive Protein (CRP)
Day 28
215 mg/L
Standard Deviation 213
141 mg/L
Standard Deviation 0

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

A normal value for IL-6 is 1.8 picograms per milliliter (pg/mL) or less. IL-6 is increased in patients with infections or chronic inflammation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

Prothrombin time is a measurement of the time it takes (in seconds) for blood to clot. A normal value is 10 to 14 seconds.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

An INR of around 1.1 is considered normal. Lower INR can means that blood is clotting faster than desired while higher INR indicates that blood is clotting slower than normal.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The aPTT test is a measurement of blood clotting time. Normal values for aPTT are around 30 to 40 seconds. Higher aPTT values can indicate a bleeding risk.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 7, 14, 21, and 28

Population: Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The anti-factor Xa assay measures plasma heparin and is useful with monitoring anticoagulation therapy. Interpretation of the resulting values depends on the anticoagulation medication used as well as the dosing schedule and indication. Patients not taking heparin should have an anti-Xa value of 0 units per milliliter (U/mL).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28

Population: This analysis includes participants who had fibrinogen assessed at the indicated time point.

Fibrinogen is a protein that helps with the formation of blood clots. For adults, the normal range of fibrinogen is 200 to 400 mg/dL. Fibrinogen can be increased in patients with liver, kidney, or inflammatory diseases. The risk of developing a thromboembolism is increased with chronically high levels of fibrinogen.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Fibrinogen
Day 1 (day of study enrollment)
934 mg/dL
Standard Deviation 79
860 mg/dL
Standard Deviation 182
Fibrinogen
Day 4 (one day after second TPE treatment)
359 mg/dL
Standard Deviation 71
807 mg/dL
Standard Deviation 199
Fibrinogen
Day 7
663 mg/dL
Standard Deviation 166
806 mg/dL
Standard Deviation 189
Fibrinogen
Day 14
593 mg/dL
Standard Deviation 143
762 mg/dL
Standard Deviation 145
Fibrinogen
Day 21
687 mg/dL
Standard Deviation 125
598 mg/dL
Standard Deviation 89
Fibrinogen
Day 28
693 mg/dL
Standard Deviation 33
116 mg/dL
Standard Deviation 0

SECONDARY outcome

Timeframe: Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28

Population: This analysis includes participants who had D-dimer at the indicated time point.

The D-dimer blood test is a method of screening for deep vein thrombosis or pulmonary embolism. A normal D-dimer value is less than 0.50 micrograms per milliliter (mcg/mL) of blood. High levels of D-dimer can occur when a patient has a major blood clot, infection, or liver disease.

Outcome measures

Outcome measures
Measure
Therapeutic Plasma Exchange (TPE)
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
n=10 Participants
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
D-dimer
Day 1 (day of study enrollment)
5187 mcg/mL
Standard Deviation 8973
1632 mcg/mL
Standard Deviation 1163
D-dimer
Day 4 (one day after second TPE treatment)
3519 mcg/mL
Standard Deviation 5575
6253 mcg/mL
Standard Deviation 9325
D-dimer
Day 7
4041 mcg/mL
Standard Deviation 6408
1749 mcg/mL
Standard Deviation 1126
D-dimer
Day 14
1819 mcg/mL
Standard Deviation 650
6767 mcg/mL
Standard Deviation 8304
D-dimer
Day 21
6765 mcg/mL
Standard Deviation 13044
3136 mcg/mL
Standard Deviation 1911
D-dimer
Day 28
16648 mcg/mL
Standard Deviation 28942
6567 mcg/mL
Standard Deviation 0

Adverse Events

Therapeutic Plasma Exchange (TPE)

Serious events: 0 serious events
Other events: 1 other events
Deaths: 2 deaths

Standard of Care

Serious events: 0 serious events
Other events: 0 other events
Deaths: 5 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Therapeutic Plasma Exchange (TPE)
n=10 participants at risk
Participants with COVID-19-associated elevated plasma viscosity randomized to receive therapeutic plasma exchange (TPE) with frozen plasma. Participants were randomized on Day 1 and received two treatments of TPE on sequential days (Day 2 and Day 3).
Standard of Care
Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.
Cardiac disorders
Mild tachycardia
10.0%
1/10 • Information on TPE-associated adverse events was collected in patients receiving the study intervention (TPE) beginning with the initiation of the first TPE and continued up to 28 days after study enrollment. Adverse events were not collected for participants in the standard of care study arm.
Adverse events were limited to TPE-associated complications of: hypotension, hypocalcemia, citrate toxicity, angiotensin-converting enzyme (ACE) inhibitor reactions, transfusion-associated circulatory overload, transfusion-related acute lung injury, transfusion-associated dyspnea, allergic reaction, hypotensive transfusion reaction, febrile non-hemolytic transfusion reaction, acute hemolytic transfusion reaction, delayed hemolytic transfusion reaction, and transfusion-transmitted infection.
0/0 • Information on TPE-associated adverse events was collected in patients receiving the study intervention (TPE) beginning with the initiation of the first TPE and continued up to 28 days after study enrollment. Adverse events were not collected for participants in the standard of care study arm.
Adverse events were limited to TPE-associated complications of: hypotension, hypocalcemia, citrate toxicity, angiotensin-converting enzyme (ACE) inhibitor reactions, transfusion-associated circulatory overload, transfusion-related acute lung injury, transfusion-associated dyspnea, allergic reaction, hypotensive transfusion reaction, febrile non-hemolytic transfusion reaction, acute hemolytic transfusion reaction, delayed hemolytic transfusion reaction, and transfusion-transmitted infection.

Additional Information

Cheryl Maier MD, PhD

Emory University

Phone: 404-712-2795

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place