Primary objectivesTo evaluate the efficacy, feasibility, viro-immunological kinetics and safety following the administration of ConvP as a therapy for outpatients diagnosed with COVID-19 at increased risk for an unfavourable clinical outcome and…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Highest disease status on the 5-point ordinal disease severity scale in the
28 days following transfusion of convP versus FFP.
Disease status is measured with a 5-point ordinal scale in which
1 = Fully recovered (no symptoms) within 7 days after transfusion
2 = Continued symptoms attributable to COVID-19 on day 7 after transfusion
3 = Admitted to hospital but no invasive ventilation needed
4 = Admitted to hospital and invasive ventilation needed
5 = Death
Secondary outcome
Evaluated in all patients:
• Number (%) of deaths in the 28 days following transfusion of convP versus FFP.
• Number (%) of hospital admissions in the 28 days following transfusion of
convP versus FFP
• Number (%) of ICU admissions in the 28 days following transfusion of convP
versus FFP
• Disease duration in days of symptoms in the 28 days following transfusion of
convP versus FFP
• Age and clinical frailty score stratified analysis of primary endpoint
following transfusion of convP versus FFP.
Evaluated in subgroups of patients:
• Change in functional decline in patients over 70 years between inclusion, day
28 and month 6 following transfusion of convP versus FFP
• Change in functional respiratory imaging, FVC and DLCOc, validated QoL
questionnaires between day 28, month 3, 6 and 12 following transfusion of convP
versus FFP
• Change in proportion of detectable SARS-CoV-2 RT-PCR results at day 3, 7, 14
and 28 following transfusion of convP versus FFP.
• Change in number (%) of anti-SARS-CoV-2 specific B-cell and CTL memory
responses at d1, d14, d28, m3, m6, m12 followin transfusion of convP versus FFP
• Number (%) of patients who fulfill the in- and exclusion criteria, number (%)
of patients asked to participate in the study, number (%) of patients who do
and do not participate and reasons to decline participation.
• Cost-effectiveness of convP compared to FFP will be assessed by calculating
the mean costs of the intervention in relation to the relative healthcare
savings of convP compared to FFP.
Exploratory endpoints:
• Highest disease status on the 5-point ordinal disease severity scale in the
28 days following transfusion of convP versus FFP according to presence of
neutralizing antibodies at baseline , symptom duration at baseline Change in
proportion of detectable SARS-CoV-2 RT-PCR results at day 3, 7, 14 and 28
following transfusion according to the presence of neutralizing antibodies at
baseline
Background summary
An effective, readily available, and safe treatment that can reduce the
duration, severity and mortality of COVID-19 is urgently needed. If effective
in the outpatient settting, this therapy could also reduce the pressure on the
health care system in the most affected regions.
Plasma from cured patients containing antibodies against SARS-COV-2 could be a
treatment for COVID-19 but its efficacy has not yet been demonstrated.
The Concovid study in the Netherlands showed that most patients are already
producing antibodies against SARS-COV-2 at the time of hospitalization. Giving
convalescent plasma at the time of hospital admission is therefore probably too
late.
The hypothesis being tested in this study is therefore that convalescent plasma
therapy is an effective treatment when given for patients at increased risk for
a more serious disease course when it is given early in the course of COVID-19.
Study objective
Primary objectives
To evaluate the efficacy, feasibility, viro-immunological kinetics and safety
following the administration of ConvP as a therapy for outpatients diagnosed
with COVID-19 at increased risk for an unfavourable clinical outcome and within
7 days after symptom onset.
Evaluated in all patients:
• To evaluate the impact of 300mL convP on mortality
• To evaluate the impact of 300mL convP on hospital admission
• To evaluate the impact of 300 mL convP on admission to ICU
• To evaluate the impact of 300mL convP on duration of symptoms
• To evaluate the impact of 300mL convP in relation to the age and clinical
frailty of the patient
Evaluated in subgroups of patients:
• To evaluate the impact of 300 mL convP on functional decline in patients aged
70 or older
• To evaluate the impact of 300 mL convP on the pulmonary condition and daily
functioning
• To evaluate the duration of viral shedding in patients with and without convp
and according to the presence of neutralizing antibodies at baseline
• To evaluate the impact of convP on the primary outcome in patients with and
without neutralizing antibodies at baseline
• To evaluate the kinetics of infection and development of cellular and humoral
anti-SARS-CoV-2 immune responses including memory immunity development.
• To evaluate the difference in efficacy of convP in relation to the duration
of symptoms at randomization
• To evaluate the feasibility of recruiting COVID-19 patients, administering
convP and perform study follow-up in an outpatient setting
• To evaluate cost-effectiveness of convP in an outpatient setting compared to
routine care
• To evaluate the duration of viral shedding in patients with and without convP
and according to the presence of neutralizing antibodies at baseline
Study design
Fase III, dubbelblind randomized
Intervention
Patients will be randomized between the transfusion of 300mL of convP versus
regular fresh frozen plasma (FFP).
Study burden and risks
Advantages of participating in this study can be; a lower risk of
hospitalization and death.
Risks of participation are the possible side effects of plasma transfusion.
These are transfusion reactions, transfusion-related lung damage (TRALI) and
the transmission of (as yet unknown) communicable diseases. Precautions are
taken against these risks
's-Gravendijkwal 230
Rotterdam 3015CE
NL
's-Gravendijkwal 230
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
• PCR-confirmed COVID-19
• Symptomatic (e.g but not limited to fatigue, fever, cough, dyspnoe, loss of
taste or smell, diarrhea, falls or confusion)
• 70 years or older OR 50-69 years and 1 or more of the risk factors described
in table 1
Table 1:
1. A/ Medical history
• Obesity with BMI 35 or higher
• Born as a male person
• History of cardiac or pulmonary disease (e.g. but not limited to atrial
fibrillation, coronary artery disease, heart failure, COPD, asthma)
• History of neurological disease (e.g. a history of stroke or any other
chronic debilitating neurological disease)
• Diabetes for which medical therapy is needed
• Chronic kidney disease with GFR <60 ml/min
• Reumatic disease (e.g. reumatoid arthritis, Systemic lupus erythematosus,
psoriatric artritis)
• Immunodeficiency (e.g. organ or allogeneic transplantation, systemic
immunosuppressive drugs)
• Cancer not in complete remission for >1 year (excluding baso -or
spinocellular skin cancers)
• Untreated HIV and CD4 T-cells <200/microliter
• Chronic liver disease, liver cirrhosis
1. B/ Lab results (if available)
• CRP > 30
• SARS-CoV-2 RT-PCR Ct value <25
Exclusion criteria
• Life expectancy <28 days in the opinion of the treating physician
• Patient or legal representative is unable to provide written informed consent
• Symptomatic for 8 days or more
• Being admitted to the hospital at the informed consent procedure
• Known previous history of transfusion-related acute lung injury
• Known IgA deficiency
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL74972.078.20 |