Evidence map›Paper›PMID 39922466›Full record

Trial reportClinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases2025

Long-term outcomes of passive immunotherapy for COVID-19: a pooled analysis of a large multinational platform randomized clinical trial.

Ahmad Mourad, Gregory A Grandits, Lianne K Siegel, Nicole Engen, Christina Barkauskas, Nnakelu Eriobu, Mamta K Jain, Tomas O Jensen, Adit Ginde, Elizabeth Higgs and 21 more

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04501978 (A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04501978 phase3completednot on this map

A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2020 to 2023Enrolled2,753ConditionsCovid19ArmsLY3819253, Placebo, Remdesivir, VIR-7831, BRII-196/BRII-198
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors.

Ahmad MouradDepartment of Medicine, Division of Infectious Diseases, Duke University School of Medicine, Durham, NC, USA; Duke Clinical Research Institute, Durham NC, USA.
Gregory A GranditsDivision of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minnesota, MN, USA.
Lianne K SiegelDivision of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minnesota, MN, USA.
Nicole EngenDivision of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minnesota, MN, USA.
Christina BarkauskasDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care, Duke University School of Medicine, Durham, NC, USA.
Nnakelu EriobuInstitute of Human Virology Nigeria, Abuja, Nigeria.
Mamta K JainDepartment of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA; Parkland Health, Dallas, TX, USA.
Tomas O JensenCentre of Excellence for Health, Immunity, and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Adit GindeDepartment of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Elizabeth HiggsNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Daniel B KnoxDivision of Pulmonary and Critical Care Medicine, Intermountain Medical Center, Murray, UT, USA.
Jonathan KitonsaMedical Research Council/Uganda Virus Research Institute, Entebbe, Uganda; London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Kami KimDivision of Infectious Disease and International Medicine, Department of Internal Medicine, University of South Florida and Tampa General Hospital, Tampa, FL, USA.
Jakob J MalinDepartment of Internal Medicine, Division of Infectious Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Vasiliki RaptiThird Department of Internal Medicine, School of Medicine, National & Kapodistrian University of Athens, Sotiria General Hospital, Athens, Greece.
D Ashley PriceDepartment of Infectious Diseases, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals Foundation Trust, Newcastle upon Tyne, United Kingdom.
Alfredo J Mena LoraDivision of Infectious Diseases, Department of Medicine, University of Illinois Chicago, Chicago, IL, USA.
Gail MathewsKirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Eleftherios MylonakisDepartment of Medicine, Houston Methodist Hospital, Houston, TX, USA.
Thomas A MurrayDivision of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minnesota, MN, USA.
Uriel SandkovskyDivision of Infectious Diseases, Department of Medicine, Baylor University Medical Center, Dallas, TX, USA.
Roger ParedesDepartment of Infectious Diseases & IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Srikanth RamachandruniChristus Spohn Hospital, Corpus Christi, TX, USA.
Cavan ReillyDivision of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minnesota, MN, USA.
David VockDivision of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minnesota, MN, USA.
John C WilliamsonDepartment of Internal Medicine, Section on Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Barnaby Edward YoungNational Centre for Infectious Diseases, Novena, Singapore; Tan Tock Seng Hospital, Novena, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Novena, Singapore.
Wesley H SelfVanderbilt Institute for Clinical & Translational Research, Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Jens LundgrenRigshospitalet, University of Copenhagen Department of Infectious Diseases, Centre of Excellence for Health, Immunity and Infections, Copenhagen, Denmark.
Thomas L HollandDepartment of Medicine, Division of Infectious Diseases, Duke University School of Medicine, Durham, NC, USA; Duke Clinical Research Institute, Durham NC, USA. Electronic address: thomas.holland@duke.edu.
INSIGHT ACTIV-3/TICO Study Group and the STRIVE Network

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
ACTIV Integration of Host-targeting Therapies for COVID-19 Administrative Coordinating CenterOT2HL156812 · NHLBI · RESEARCH TRIANGLE INSTITUTE · PI NOLEN, TRACY L, THOMAS, SONIA M · 2020 to 2024
$1270.7M
NCI NIH HHS 75N91019D00024NHLBI NIH HHS OT2 HL156812
6 · The paper itself

Abstract

objectivesPassive immunotherapy, including monoclonal antibodies and neutralizing proteins, was used for the treatment of patients with COVID-19 during the pandemic. Accelerating COVID-19 Therapeutic Interventions and Vaccines-Therapeutics for Inpatients with COVID-19 (ACTIV-3/TICO) was a multinational, randomized placebo-controlled platform trial that evaluated the effectiveness of multiple passive immunotherapy agents in patients hospitalized with COVID-19. Given the long half-life of some agents studied, participants were followed for an extended period to assess the long-term efficacy and sustained safety of these agents.

methodsWe conducted a pooled analysis of individual participant data from four trials of ACTIV-3/TICO: sotrovimab, amubarvimab-romlusevimab, tixagevimab-cilgavimab, and ensovibep. Cox proportional hazards models were conducted to compare time to mortality and time to mortality or rehospitalization between participants receiving active agents vs. placebo through 18 months.

resultsA total of 2311 participants were enrolled between 16 December 2020 and 15 November 2021. Overall, 56.9% (1315/2311) received an active agent and 77.2% (1784/2311) of participants were unvaccinated for SARS-CoV-2. Median duration between symptom onset and enrolment was 8 days (interquartile range, 6-10), and most participants received remdesivir (92.1% [2129/2311]) and corticosteroids (70.4% [1627/2311]) before enrolment. There was no difference in mortality across all active (11.9% [157/1315]) vs. placebo (14.0% [139/996]) arms (hazard ratio, 0.87; 95% CI, 0.70-1.08). Furthermore, there was no difference in combined mortality or rehospitalization across all active (31.7% [417/1315]) vs. placebo (32.1% [320/996]) arms (hazard ratio, 0.96; 95% CI, 0.84-1.10). DISCUSSION: In our large study of long half-life passive immunotherapy for hospitalized patients with COVID-19, we did not find evidence of a long-term effect on either mortality or rehospitalization.

trial registrationNCT04501978.

Indexed as

COVID-19Immunization, PassiveAdultAgedAntibodies, MonoclonalAntibodies, NeutralizingCOVID-19 Drug TreatmentFemaleHumansMaleMiddle AgedSARS-CoV-2Treatment OutcomeAntibodies, MonoclonalAntibodies, NeutralizingCOVID-19Monoclonal antibodiesNeutralizing antibodiesPassive immunotherapySARS-CoV-2

Identifiers

PMID39922466
PMCPMC12068974

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.