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NCT04441996

Therapeutic Plasma Exchange for COVID-19-associated Hyperviscosity

Completed Phase 4 Results posted Last updated 21 December 2022
What this trial tests

Phase 4 trial testing Therapeutic plasma exchange (TPE) in COVID-19 in 20 participants. Completed in 18 March 2021.

Timeline
17 July 2020
Primary endpoint
18 March 2021
18 March 2021

Quick facts

Lead sponsorEmory University
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment20
Start date17 July 2020
Primary completion18 March 2021
Estimated completion18 March 2021
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Emory University

Who can join

18 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Plasma Viscosity Primary · 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.

Baseline
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)2.35± 0.37
Standard of Care2.47± 0.34
Post-treatment
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)1.61± 0.09
Standard of Care2.47± 0.48
Cumulative Incidence of Adverse Events Primary · Up to Day 28

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.

GroupValue95% CI
Therapeutic Plasma Exchange (TPE)1
Cumulative All Cause Mortality Secondary · Up to Day 28

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

Day 1 to Day 3
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)0
Standard of Care0
Day 1 to Day 7
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)0
Standard of Care0
Day 1 to Day 14
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)0
Standard of Care2
Day 1 to Day 21
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)1
Standard of Care4
Day 1 to Day 28
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)2
Standard of Care5
Cumulative Count of Bleeding and Thromboembolic Complications Secondary · 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.

Day 1 to Day 3
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)0
Standard of Care0
Day 1 to Day 7
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)1
Standard of Care0
Day 1 to Day 14
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)1
Standard of Care0
Day 1 to Day 21
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)2
Standard of Care2
Day 1 to Day 28
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)2
Standard of Care2
Time to Treatment Failure Secondary · Up to Day 28

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.

GroupValue95% CI
Therapeutic Plasma Exchange (TPE)5.5± 2.12
Standard of Care2.5± 3.54
Duration of ICU Stay Secondary · 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.

GroupValue95% CI
Therapeutic Plasma Exchange (TPE)23.1± 15.7
Standard of Care16.0± 11.4
Duration of Hospital Stay Secondary · 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.

GroupValue95% CI
Therapeutic Plasma Exchange (TPE)27.2± 12.4
Standard of Care21.7± 12.0
Discharge Disposition Secondary · 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.

GroupValue95% CI
Therapeutic Plasma Exchange (TPE)7
Standard of Care5
Therapeutic Plasma Exchange (TPE)3
Standard of Care5
Clinical Status Score Secondary · 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

Day 1 (day of study enrollment)
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)7.06.0 – 7.75
Standard of Care8.07.25 – 8.0
Day 4 (1 day after second TPE treatment)
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)7.06.0 – 7.0
Standard of Care8.07.25 – 8.0
Day 7
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)7.06.0 – 8.0
Standard of Care8.07.0 – 8.0
Day 14
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)8.06.0 – 8.0
Standard of Care7.57.0 – 9.75
Day 21
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)7.55.5 – 8.0
Standard of Care8.07.0 – 12.0
Day 28
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)7.05.5 – 8.75
Standard of Care10.07.0 – 12.0
Ventilator Days Secondary · Up to Day 28

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

GroupValue95% CI
Therapeutic Plasma Exchange (TPE)22.6± 11.6
Standard of Care19.2± 11.2
Positive End-Expiratory Pressure (PEEP) Secondary · Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28

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.

Day 1 (day of study enrollment)
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)12.7± 5.0
Standard of Care15.9± 5.9
Day 4 (one day after second TPE treatment)
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)11.6± 4.3
Standard of Care13.0± 3.7
Day 7
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)13.0± 6.2
Standard of Care11.3± 3.9
Day 14
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)13.0± 2.0
Standard of Care13.3± 2.7
Day 21
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)11.0± 1.2
Standard of Care11.0± 2.0
Day 28
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)11.0± 2.6
Standard of Care12.7± 7.0
Sequential Organ Failure Assessment (SOFA) Score Secondary · Day 1 (day of study enrollment), Day 4 (one day after second TPE treatment), Days 7, 14, 21, and 28

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.

Day 1 (day of study enrollment)
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)10.58.5 – 12.75
Standard of Care13.011.25 – 14.0
Day 4 (one day after second TPE treatment)
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)11.07.75 – 12.5
Standard of Care11.511.0 – 12.75
Day 7
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)11.010.0 – 12.0
Standard of Care12.011.25 – 13.75
Day 14
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)12.58.75 – 13.75
Standard of Care12.511.0 – 15.0
Day 21
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)11.58.75 – 12.0
Standard of Care13.010.75 – 15.75
Day 28
GroupValue95% CI
Therapeutic Plasma Exchange (TPE)11.58.25 – 12.75
Standard of Care12.09.0 – 15.75

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Therapeutic Plasma Exchange (TPE)
Serious: 0/10 (0%)
Deaths: 2/10
Standard of Care
Serious: 0
Deaths: 5/10
Other adverse events (1 terms — click to expand)

ReactionSystemTherapeutic Plasma Exchang…Standard of Care
Mild tachycardiaCardiac disorders

Data from ClinicalTrials.gov NCT04441996 adverse events section.

Sponsor's own description

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).

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication.
    Ning Q, Wu D, Wang X, Xi D, et al · · 2022 · cited 64× · PMID 35197452 · DOI 10.1038/s41392-022-00907-1
  2. COVID-19 and thrombotic microangiopathies.
    Tiwari NR, Phatak S, Sharma VR, Agarwal SK. · · 2021 · cited 64× · PMID 33894421 · DOI 10.1016/j.thromres.2021.04.012
  3. Therapeutic plasma exchange for COVID-19-associated hyperviscosity.
    Truong AD, Auld SC, Barker NA, Friend S, et al · · 2021 · cited 43× · PMID 33231313 · DOI 10.1111/trf.16218
  4. An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19).
    Elahi R, Karami P, Heidary AH, Esmaeilzadeh A. · · 2022 · cited 33× · PMID 35074571 · DOI 10.1016/j.intimp.2022.108536
  5. The interplay between inflammation and thrombosis in COVID-19: Mechanisms, therapeutic strategies, and challenges.
    Ma L, Willey J. · · 2022 · cited 17× · PMID 38620713 · DOI 10.1016/j.tru.2022.100117
  6. Blood hyperviscosity in acute and recent COVID-19 infection.
    Shaik A, Chen Q, Mar P, Kim H, et al · · 2022 · cited 16× · PMID 35466930 · DOI 10.3233/ch-221429
  7. COVID-19 and arterial thrombosis: A potentially fatal combination.
    Moroni F, Baldetti L. · · 2021 · cited 8× · PMID 33091523 · DOI 10.1016/j.ijcard.2020.10.046

Verify or expand the search:

Other trials of Therapeutic plasma exchange (TPE)

Trials testing the same drug.

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Currently open trials in the same condition.

Other Emory University trials

Trials by the same sponsor.

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