A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial

Abstract Background The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. Methods DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. Discussion This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration ClinicalTrials.govNCT04429854. Registered on 12 June 2020 - Retrospectively registered.

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A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial.

10.21203/rs.3.rs-45324/v2 ◽

2020 ◽

Author(s):

Timothy Devos ◽

Tatjana Geukens ◽

Alexander Schauwvlieghe ◽

Kevin K Ariën ◽

Cyril Barbezange ◽

...

Keyword(s):

Treatment Group ◽

Phase Ii ◽

Clinical Efficacy ◽

Active Treatment ◽

Standard Of Care ◽

Active Treatment Group ◽

Proof Of Concept ◽

Efficacy And Safety ◽

Open Label ◽

Open Label Phase

Abstract Background:The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease, showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown.Methods:DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 hours before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 hours after randomization, with a second administration of 2 units 24 to 36 hours after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma.Discussion:This trial will either provide support or discourage the use of convalescent plasma as early intervention for the treatment of hospitalized patients with COVID-19 infection.Trial registration: Clinicaltrials.gov, Identifier: NCT04429854. Registered 12 June 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04429854.

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A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial.

10.21203/rs.3.rs-45324/v1 ◽

2020 ◽

Author(s):

Timothy Devos ◽

Tatjana Geukens ◽

Alexander Schauwvlieghe ◽

Kevin K Ariën ◽

Cyril Barbezange ◽

...

Keyword(s):

Treatment Group ◽

Phase Ii ◽

Clinical Efficacy ◽

Active Treatment ◽

Standard Of Care ◽

Active Treatment Group ◽

Proof Of Concept ◽

Efficacy And Safety ◽

Open Label ◽

Open Label Phase

Abstract Background: The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease, showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown.Methods: DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 hours before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 hours after randomization, with a second administration of 2 units 24 to 36 hours after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma.Discussion: This trial will either provide support or discourage the use of convalescent plasma as early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration: Clinicaltrials.gov, Identifier: NCT04429854. Registered 12 June 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04429854.

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Correction to: A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial

Trials ◽

10.1186/s13063-020-04947-2 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Timothy Devos ◽

Tatjana Geukens ◽

Alexander Schauwvlieghe ◽

Kevin K. Ariën ◽

Cyril Barbezange ◽

...

Keyword(s):

Phase Ii ◽

Clinical Efficacy ◽

Standard Of Care ◽

Proof Of Concept ◽

Efficacy And Safety ◽

Open Label ◽

Open Label Phase

An amendment to this paper has been published and can be accessed via the original article.

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A multicenter, open-label, randomized, proof-of-concept phase ii clinical trial to Assess the efficacy and safety of icatibant in patients infected with sars-cov-2 (covid-19) And admitted to hospital units without invasive mechanical ventilation. StudyProtocol (icat-covid)

10.21203/rs.3.rs-775895/v1 ◽

2021 ◽

Author(s):

Aurema Otero González ◽

Pierre Malchair ◽

Jordi Giol ◽

Xavier Solanich ◽

Thiago Carnaval ◽

...

Keyword(s):

Clinical Trial ◽

Mechanical Ventilation ◽

Phase Ii ◽

Invasive Mechanical Ventilation ◽

Standard Of Care ◽

Proof Of Concept ◽

Efficacy And Safety ◽

Open Label ◽

Number Of Patients ◽

Experimental Group

Abstract Background: COVID-19 has quickly become a global pandemic with a substantial number of deaths and a substantial burden for healthcare systems worldwide. Although most cases are paucisymptomatic and limited to the viral infection related symptoms, some patients evolve to a second phase, with an impaired inflammatory response (cytokine storm) that may lead to acute respiratory distress syndrome and death. This is thought to be caused by an increased bradykinin synthesis. Methods: ICAT-COVID is a multicenter, randomized, open-label, proof-of-concept phase II clinical trial assessing the clinical efficacy and safety of adding Icatibant on the standard of care in patients hospitalized with COVID-19 without invasive mechanical ventilation. Patients hospitalized with a confirmed COVID-19 pneumonia diagnosis (RT-PCR or antigen test ≤ 10 days prior to randomization, and radiographic evidence of pulmonary infiltrates), rated ‘4’ or ‘5’ on the WHO’s clinical status scale are eligible. Patients will be randomized on a 1:1 ratio to either standard of care-plus-Icatibant (experimental group) or to standard of care alone (control group). The experimental group will receive 30 mg of Icatibant subcutaneously 3 times a day for 3 days (for a total of 9 doses). The expected sample size is of 120 patients (60 per group) gathered from 2 centers in Spain. Primary outcomes are Icatibant’s efficacy and safety. The main efficacy outcome is the number of patients reaching grades ‘2’ or ‘1’ on the WHO Scale within 10 days of treatment start. Among the secondary outcomes are ‘long-term efficacy’: number of patients discharged who do not present any COVID-19-related relapse or comorbidity up until 28 days after discharging, and mortality. Discussion: Icatibant, a bradykinin type 2 receptor antagonist with proven effectiveness and safety against hereditary angioedema attacks, may be beneficial for COVID-19 patients by inhibiting bradykinin’s action on endothelial cells and by inhibiting the SARS-CoV-2 M protease. Our working hypothesis is that treatment with Standard of Care-plus-Icatibant is effective and safe to treat patients infected with SARS-CoV-2 admitted to hospital for pneumonia without invasive mechanical ventilation.Trial registration: EudraCT: 2020-002166-13; ClinicalTrials.gov: NCT04978051

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