Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04355897 |
| Other study ID # |
20-23 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
April 28, 2020 |
| Est. completion date |
August 12, 2020 |
Study information
| Verified date |
January 2024 |
| Source |
The Christ Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The investigatores propose to evaluate intravenous administration of convalescent plasma (CP)
obtained from COVID19 survivors in patients requiring hospitalization for symptomatic "high
risk" COVID19 disease as reflected by the presence of elevated hsTPN. Supportive data exist
for use of convalescent plasma in the treatment of COVID19 and other overwhelming viral
illness. Investigators hypothesize that treatment with COVID19 CP will demonstrate salutary
effects on COVID19 disease severity/duration, with the primary objective to reduce mortality
and a key secondary objective to reduce the requirement for and/or duration of mechanical
ventilation. Finally, as the hospital mortality for patients requiring mechanical ventilation
is very high (50 to 80%), these patients will be eligible for COVID19 CP treatment as well,
even in the absence of elevated hsTPN. Although considerable overlap of these populations has
been observed (elevated hsTPN and requirement for mechanical ventilation) there is not 100%
redundancy and it is hopeful that COVID19 CP may provide benefit to these critically ill
patients.
Description:
Coronavirus's are responsible for 15-30% of "common colds" and approximately 2% of the
population may be healthy carriers of these viruses. The ongoing SARS CoV-2 pandemic
originated in Wuhan, Hubei, China and has spread worldwide. The disease caused by SARS CoV-2
(COVID19) is manifest by fever, fatigue, dry cough, pharyngitis and headache. Although the
majority (~80%) COVID19 cases are mild in severity, patients may present with moderate
symptoms of dyspnea, tachypnea (~15%) or more severe symptoms (~5-10%) of pneumonia, acute
respiratory distress syndrome (ARDS), hypotension, arrythmias and shock(6-9). In addition to
the common clinical presentation of respiratory distress, an increasing frequency of
cardiovascular manifestations have become evident. These manifestations may be linked to the
Angiotensin Converting Enzyme-2 (ACE-2) receptor, a membrane-bound aminopeptidase that has
been identified as the functional receptor for SARS CoV-2, which is expressed predominantly
in the heart, intestine, kidney and pulmonary alveolar (type 2) cells. Recent data suggest
that ~20% of infected subjects may require hospitalization and among patients hospitalized
for COVID19, 12-28% will have evidence of myocardial injury (elevated high-sensitivity
Troponin: hsTPN) often in association with electrocardiographic (ECG) abnormalities,
arrythmias and/or evidence for impaired Left Ventricular contractile function on non-invasive
imaging. Indeed, a syndrome of "pseudo-infarction" manifest as ST-segment elevation in the
absence of obstructive coronary artery disease has been described. The etiology(s) of
myocardial injury may be multifactorial and includes demand ischemia due to critical illness,
cytokine storm with atherosclerotic plaque disruption due to overwhelming systemic
inflammation and more likely, myocarditis. Indeed, SARS CoV viral RNA along with macrophage
infiltration and myocardial cell injury has been detected in autopsied heart samples from
patients who succumbed to the SARS outbreak in Toronto. Further, myocardial injury has been
directly correlated with both the degree of systemic inflammation (Level of hsCRP) and
cardiac dysfunction (level of NT-proBNP). Importantly, myocardial injury was identified to be
one of the two most significant, independent predictors (by multi-variable analysis) of
hospital death (in addition to ARDS) and provides increased prognostic information above and
beyond that provided by pre-existing co-morbidities including age, diabetes mellitus,
hypertension and pre-existing cardiovascular disease. Indeed, the incremental risk for death
incurred by evidence of myocardial injury appears to be ~5-10x and is amplified by
pre-existing cardiovascular disease.
Thus, evidence of myocardial injury has evolved to be a significant (if not the most
significant) predictor of mortality among patients admitted to hospital for care of COVID19
disease. It is important to recognize that this elevated morality risk has been identified
despite modern and aggressive intensive care therapies including mechanical ventilation,
pressor/inotrope therapies and extracorporeal membrane oxygenation (ECMO).
In this context, the investigators propose to evaluate intravenous administration of
convalescent plasma (CP) obtained from COVID19 survivors in patients requiring
hospitalization for symptomatic "high risk" COVID19 disease as reflected by the presence of
elevated hsTPN. Supportive data exist for use of convalescent plasma in the treatment of
COVID19 and other overwhelming viral illness. The investigators hypothesize that treatment
with COVID19 CP will demonstrate salutary effects on COVID19 disease severity/duration, with
the primary objective to reduce mortality and a key secondary objective to reduce the
requirement for and/or duration of mechanical ventilation. Finally, as the hospital mortality
for patients requiring mechanical ventilation is very high (50 to 80%), these patients will
be eligible for COVID19 CP treatment as well, even in the absence of elevated hsTPN. Although
considerable overlap of these populations has been observed (elevated hsTPN and requirement
for mechanical ventilation) there is not 100% redundancy and it is hopeful that COVID19 CP
may provide benefit to these critically ill patients.
This is a single arm, non-randomized, open-label treatment of eligible subjects defined as
those who satisfy all inclusion criteria.
Eligible subjects will provide written, informed consent prior to participation. A pregnancy
test will be obtained on all women of child-bearing potential. Following informed consent,
the following baseline laboratory tests will be obtained:
- Hs-CRP
- D-Dimer
- NT-pro BNP
These laboratory tests which reflect inflammation, thrombosis and myocardial dysfunction (in
addition hsTPN which reflects myocardial necrosis) will be repeated every 2 days during
hospitalization. Following baseline assessments and informed consent, eligible enrollees will
receive convalescent CoVID-19 plasma by intravenous infusion.
COVID-19 Convalescent Plasma Study: Convalescent plasma will be obtained from male donors,
nulliparous females, or female donors negative for HLA antibodies at least 28 days following
recovery from COVID-19 infection. These donors are used to minimize the risk of
transfusion-related acute lung injury (TRALI). Routine ABO and Rh typing and red cell
antibody screening will be performed. All plasma will be required to test negative to the
following assays per FDA and AABB regulations/ guidelines.
COVID Convalescent Plasma 500 mls will be administered in intravenously.
