Covid-19 Living Data

Trial NCT04518410
Publication ACTIV-2/A5401 - Chew K, Nat Commun (2022) (published paper)
Dates: 2020-10-12 to 2020-11-17
Funding: Mixed (National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Study medication was donated by Eli Lilly and Company.)
Conflict of interest: Yes

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / USA Follow-up duration (days): 168
Inclusion criteria	Adults 18 years of age or older documented SARS-CoV-2 infection by an FDA-authorized antigen or nucleic acid test from a sample collected within 7 days prior to anticipated study entry no more than 10 days of COVID-19 symptoms at time of anticipated study entry ongoing symptoms (not including loss of taste or smell) within 48 hours prior to study entry resting peripheral oxygen saturation levels >=92% without the need for hospitalization
Exclusion criteria	History of or current hospitalization for COVID-19 Any positive SARS-CoV2 nucleic acid or antigen tests from any respiratory tract specimen (e.g., oropharyngeal, NP, or nasal swab, or saliva) collected ˃240 hours prior to study entry Current need for hospitalization or immediate medical attention in the clinical opinion of the site investigator Use of any prohibited medication: hydroxychloroquine (unless used chronically for autoimmune diseases), chloroquine (unless used for a parasitic infection), ivermectin (unless used for a parasitic infection), any antibody-based therapy for COVID-19, remdesivir, fluvoxamine (unless used chronically), colchicine (unless used for reasons other than COVID-19), and HIV protease inhibitors (unless used chronically for HIV infection) and/or use of systemic or inhaled steroids for the purpose of COVID-19 treatment (new or increased dose from chronic baseline) within 30 days prior to study entry Receipt of convalescent COVID-19 plasma or other antibody-based anti-SARS-CoV-2 treatment or prophylaxis at any time prior to study entry Receipt of other available investigational treatments for SARS-CoV-2 at any time prior to study entry. This does not include drugs approved for other uses and taken for those uses. NOTE: This does not include COVID-19 vaccines Known allergy/sensitivity or any hypersensitivity to components of the investigational agent or placebo Any co-morbidity requiring surgery within 7 days prior to study entry, or that is considered life threatening in the opinion of the site investigator within 30 days prior to study entry Currently pregnant or breastfeeding
Interventions
	Treatment Bamlanivimab 700 mg intravenously over 60 minutes
	Control Placebo
Participants
	Randomized participants : Placebo=110 Bamlanivimab=110
	Characteristics of participants N= 220 Mean age : NR 110 males Severity : Mild: n= 225/ Asymptomatic: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register 1) COVID-19 symptom duration (Phase 2) [ Time Frame: Up to Day 28 ]; 2) Quantification of SARS-CoV-2 RNA (Phase 2) [ Time Frame: Day 3, 7, 14 ]; 3) Proportion of participants with new adverse event (AE) ≥ Grade 3 (Phase 2) [ Time Frame: Thru Day 28 ];
	In the report 1) development of a Grade 3 or higher treatment emergent adverse event (TEAE) through 28 days; 2) detection (detectable versus undetectable)of SARS-CoV-2 RNA from NP swabs at days 3, 7, 14, 21, and 28; 3) duration of targeted COVID-19-associated symptoms from day 0.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
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 pre-print article, the trial registry and the overall adaptive platform trial protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. Supplementary materials referred to in the pre-print article were not available at time of extraction. There were minor differences between some primary outcomes in the article and the registry (an additional 28 day timepoint for RT-PCR in the article; additional 21 and 28 day timepoint for of detection (detectable versus undetectable) of SARS-CoV-2 RNA from NP swabs in the article; adverse events were only a phase 3 outcome in the registry); additional primary outcomes in the article were secondary outcomes in the registry. Two participants analyzed in the intervention group were originally randomized to the 7000mg versus placebo cohort in this platform study, but received 700mg in error and were analyzed in the 700mg bamlanivimab cohort. Two participants analyzed in the placebo group were also originally in the 7000mg versus placebo cohort study, but were analyzed against the 700mg group. The study (n=222) achieved the target sample size (n=220) specified in the protocol. This study was updated on November 18th, 2022 with data extracted from the peer-reviewed report.