Trial NCT04521309
Publication Ali S, EClinicalMedicine , 2021 (published paper)
Dates: 2020-06-19 to 2021-02-03
Funding: Public/non profit (Higher Education Commission (HEC), Pakistan)
Conflict of interest: No
| Methods | |
| RCT Blinding: single blinding | |
| Location :
Single center / Pakistan Follow-up duration (days): 28 | |
| Inclusion criteria | Above 18 years of age; positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs; admitted to the clinical trial site approved tertiary care hospital (isolation ward and ICU); either severely (hospitalized, requiring any supplemental oxygen) or critically (hospitalized, requiring non-invasive ventilation, high-flow oxygen devices or invasive ventilation) ill with Acute Respiratory Distress Syndrome (ARDS) i.e. dyspnea, respiratory rate >=30/min, blood oxygen saturation =<90%, PaO2/FiO2 <300, and lung infiltrates >50% on chest X-ray |
| Exclusion criteria | A history of IgA deficiency, autoimmune disorder, thromboembolic disorder, or allergic reaction to immunoglobulin treatment; pregnant females; patients requiring two or more inotropic agents to maintain blood pressure; patients with acute or chronic kidney injury/failure; known case of thromboembolic disorder; aseptic meningitis |
| Interventions | |
| Treatment
Hyperimmune anti-COVID-19 Intravenous Immunoglobulin 0.15-0.3 g/Kg IV once-off |
|
| Control
Standard care ( / ) Definition of Standard care: All participants, irrespective of their group assignment, received SOC according to the national clinical management guideline for COVID-19 Infection which includes airway support, antiviral medications, anticoagulant, steroid, hemodynamic support and antibiotics when required [12]. SOC included Remdesivir (200 mg loading then 100 mg once daily for 5 days), Enoxaparin and corticosteroids, dexamethasone (6 mg once daily) or Methylprednisolone (0.51 mg/kg twice daily) initiated at the time of hospitalization till resolution of ARDS. | |
| Participants | |
| Randomized 50 participants (n1=40 / n2= 10) | |
| Characteristics of participants N=50 Mean age : 56.5 35 males Severity : Mild: n=0 / Moderate: n=22/ Severe: n=27 Critical: n=1 | |
| Primary outcome | |
| In the register 28 Days mortality; Requirement of supplemental oxygen support; Number of days on assisted ventilation; Days to step down; Days to Hospital Discharge; Adverse events during hospital stay; Change in C-Reactive Protein (CRP) levels; Change in neutrophil lymphocyte ratio | |
| In the report 28-day mortality; clinical status; PaO2/FiO2 ratio | |
| Documents available |
Protocol Yes. In English Statistical plan NR Data-sharing stated
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| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | In addition to the published article, the study registry and protocol were used in data extraction and risk of bias assessment. The registration was made 2 months after start of recruitment, but nearly 6 months before the end of the study, with no changes to outcomes. The dosages in the registry were changed after completion of the study. The primary outcomes in the report (28-day mortality, patient's clinical status during study duration and Horowitz index at outcome day) are not the same as those in the registry (28 days mortality, requirement of supplemental oxygen support, number of days on assisted ventilation, days to step down and to hospital discharge, adverse events during hospital stay, change in C-Reactive Protein levels, and change in neutrophil lymphocyte ratio; time frame: 28 days). The ordinal scale on which discharge and WHO score 7 or above outcome data are based was not included in the registry or protocol. The article reports a small phase I/II trial that achieved its target sample size. |