Therapeutics
The goal of ACTIV is to develop a research strategy for prioritizing and speeding development of the most promising COVID-19 vaccines and treatments.
Overview
The Therapeutics Clinical Working Group is focused on:
- Establishing a steering committee with relevant expertise to set criteria for and rank potential candidates submitted by industry partners for testing
- Developing a complete inventory of potential candidates with different mechanisms of action and acceptable safety profiles
- Designing, launching and openly sharing master protocols with agreed-upon endpoints, sampling and analysis for evaluating candidates
- Using a single control arm to enhance trial efficiency
Lessons Learned
Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines-Selecting Compounds for Clinical Evaluation in Coronavirus Disease 2019 Clinical Trials. Buchman TG, Draghia-Akli R, Adam SJ, Aggarwal NR, Fessel JP, Higgs ES, Menetski JP, Read SW, Hughes EA; Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines (ACTIV) Therapeutics Clinical Working Group.Crit Care Med. 2021 Nov 1;49(11):1963-1973. doi: 10.1097/CCM.0000000000005295.PMID: 34495876
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV): Designing Master Protocols for Evaluation of Candidate COVID-19 Therapeutics. LaVange L, Adam SJ, Currier JS, Higgs ES, Reineck LA, Hughes EA, Read SW; ACTIV Therapeutics-Clinical Working Group.Ann Intern Med. 2021 Sep;174(9):1293-1300. doi: 10.7326/M21-1269. Epub 2021 Jun 29.PMID: 34181444
Publications
Heterogeneous Treatment Effects of Therapeutic-Dose Heparin in Patients Hospitalized for COVID-19. Goligher EC, Lawler PR, Jensen TP, Talisa V, Berry LR, Lorenzi E, McVerry BJ, Chang CH, Leifer E, Bradbury C, Berger J, Hunt BJ, Castellucci LA, Kornblith LZ, Gordon AC, McArthur C, Webb S, Hochman J, Neal MD, Zarychanski R, Berry S, Angus DC; REMAP-CAP, ATTACC, and ACTIV-4a Investigators.
JAMA. 2023 Mar 21. doi: 10.1001/jama.2023.3651. Online ahead of print. PMID: 36942550
Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization. Wang TY, Wahed AS, Morris A, Kreuziger LB, Quigley JG, Lamas GA, Weissman AJ, Lopez-Sendon J, Knudson MM, Siegal DM, Kasthuri RS, Alexander AJ, Wahid L, Atassi B, Miller PJ, Lawson JW, Patel B, Krishnan JA, Shapiro NL, Martin DE, Kindzelski AL, Leifer ES, Joo J, Lyu L, Pennella A, Everett BM, Geraci MW, Anstrom KJ, Ortel TL; ACTIV-4C Study Group. Ann Intern Med. 2023 Mar 21. doi: 10.7326/M22-3350. Online ahead of print. PMID: 36940444
Heterogeneous Treatment Effects of Therapeutic-Dose Heparin in Patients Hospitalized for COVID-19. Goligher EC, Lawler PR, Jensen TP, Talisa V, Berry LR, Lorenzi E, McVerry BJ, Chang CH, Leifer E, Bradbury C, Berger J, Hunt BJ, Castellucci LA, Kornblith LZ, Gordon AC, McArthur C, Webb S, Hochman J, Neal MD, Zarychanski R, Berry S, Angus DC; REMAP-CAP, ATTACC, and ACTIV-4a Investigators. JAMA. 2023 Mar 21. doi: 10.1001/jama.2023.3651. Online ahead of print. PMID: 36942550
Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization. Wang TY, Wahed AS, Morris A, Kreuziger LB, Quigley JG, Lamas GA, Weissman AJ, Lopez-Sendon J, Knudson MM, Siegal DM, Kasthuri RS, Alexander AJ, Wahid L, Atassi B, Miller PJ, Lawson JW, Patel B, Krishnan JA, Shapiro NL, Martin DE, Kindzelski AL, Leifer ES, Joo J, Lyu L, Pennella A, Everett BM, Geraci MW, Anstrom KJ, Ortel TL; ACTIV-4C Study Group. Ann Intern Med. 2023 Mar 21. doi: 10.7326/M22-3350. Online ahead of print. PMID: 36940444
Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial. Naggie S, Boulware DR, Lindsell CJ, Stewart TG, Slandzicki AJ, Lim SC, Cohen J, Kavtaradze D, Amon AP, Gabriel A, Gentile N, Felker GM, Jayaweera D, McCarthy MW, Sulkowski M, Rothman RL, Wilson S, DeLong A, Remaly A, Wilder R, Collins S, Dunsmore SE, Adam SJ, Thicklin F, Hanna GJ, Ginde AA, Castro M, McTigue K, Shenkman E, Hernandez AF; Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators. JAMA. 2023 Mar 21;329(11):888-897. doi: 10.1001/jama.2023.1650. PMID: 36807465
Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19. Mylonakis E, Barkauskas C, Poulakou G, Young BE; ACTIV-3/TICO Study Group*. Ann Intern Med. 2023 Feb;176(2):eL220456. doi: 10.7326/L22-0456. PMID: 36802896 No abstract available.
Symptom and Viral Rebound in Untreated SARS-CoV-2 Infection. Deo R, Choudhary MC, Moser C, Ritz J, Daar ES, Wohl DA, Greninger AL, Eron JJ, Currier JS, Hughes MD, Smith DM, Chew KW, Li JZ; ACTIV-2/A5401 Study Team. Ann Intern Med. 2023 Mar;176(3):348-354. doi: 10.7326/M22-2381. Epub 2023 Feb 21. PMID: 36802755 Clinical Trial.
Qualitative interviews to evaluate content validity of the ACTIV-2 COVID-19 Symptom Diary (ACSD). Matza LS, Stewart KD, Naegeli AN, Mills KM, Coyne KS, Chew KW, Hughes MD, Smith DM. J Patient Rep Outcomes. 2023 Jan 31;7(1):8. doi: 10.1186/s41687-022-00535-x. PMID: 36719546 Free PMC article.
Phase 2 safety and antiviral activity of SAB-185, a novel polyclonal antibody therapy for non-hospitalized adults with COVID-19. Taiwo BO, Chew KW, Moser C, Wohl DA, Daar ES, Li JZ, Greninger AL, Bausch C, Luke T, Hoover K, Neytman G, Giganti MJ, Olefsky M, Javan AC, Fletcher CV, Eron JJ, Currier JS, Hughes MD, Smith DM; ACTIV-2/A5401 Study Team. J Infect Dis. 2023 Jan 20:jiad013. doi: 10.1093/infdis/jiad013. Online ahead of print. PMID: 36661240
Publisher Correction: Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults with COVID-19. Chew KW, Moser C, Daar ES, Wohl DA, Li JZ, Coombs RW, Ritz J, Giganti M, Javan AC, Li Y, Choudhary MC, Deo R, Malvestutto C, Klekotka P, Price K, Nirula A, Fischer W, Bala V, Ribeiro RM, Perelson AS, Fletcher CV, Eron JJ, Currier JS; ACTIV-2/A5401 Study Team; Hughes MD, Smith DM. Nat Commun. 2023 Jan 19;14(1):333. doi: 10.1038/s41467-023-35835-3. PMID: 36658128 Free PMC article. No abstract available.
Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial. McCarthy MW, Naggie S, Boulware DR, Lindsell CJ, Stewart TG, Felker GM, Jayaweera D, Sulkowski M, Gentile N, Bramante C, Singh U, Dolor RJ, Ruiz-Unger J, Wilson S, DeLong A, Remaly A, Wilder R, Collins S, Dunsmore SE, Adam SJ, Thicklin F, Hanna G, Ginde AA, Castro M, McTigue K, Shenkman E, Hernandez AF; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators. JAMA. 2023 Jan 24;329(4):296-305. doi: 10.1001/jama.2022.24100. PMID: 36633838
Effect of Ivermectin 600 μg/kg for 6 days vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial. Naggie S, Boulware DR, Lindsell CJ, Stewart TG, Lim SC, Cohen J, Kavtaradze D, Amon AP, Gabriel A, Gentile N, Felker GM, Rothman RL, Jayaweera D, McCarthy MW, Sulkowski M, Wilson S, DeLong A, Remaly A, Wilder R, Collins S, Dunsmore SE, Adam SJ, Thicklin F, Hanna GJ, Ginde AA, Castro M, McTigue K, Shenkman E, Hernandez AF; Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators. medRxiv. 2022 Dec 15:2022.12.15.22283488. doi: 10.1101/2022.12.15.22283488. Preprint. PMID: 36561174 Free PMC article. Updated.
Predictors of SARS-CoV-2 RNA From Nasopharyngeal Swabs and Concordance With Other Compartments in Nonhospitalized Adults With Mild to Moderate COVID-19. Moser C, Li JZ, Eron JJ, Aga E, Daar ES, Wohl DA, Coombs RW, Javan AC, Bender Ignacio RA, Jagannathan P, Ritz J, Sieg SF, Parikh UM, Hughes MD, Currier JS, Smith DM, Chew KW; ACTIV-2/A5401 Study Team. Open Forum Infect Dis. 2022 Nov 11;9(11):ofac618. doi: 10.1093/ofid/ofac618. eCollection 2022 Nov. PMID: 36467293 Free PMC article.
Infliximab as a potential treatment for COVID-19. Velez MP, McCarthy MW. Expert Rev Anti Infect Ther. 2023 Jan;21(1):1-5. doi: 10.1080/14787210.2023.2151438. Epub 2022 Nov 27. PMID: 36413380 Clinical Trial.
Bamlanivimab therapy for acute COVID-19 does not blunt SARS-CoV-2-specific memory T cell responses. Ramirez SI, Grifoni A, Weiskopf D, Parikh UM, Heaps A, Faraji F, Sieg SF, Ritz J, Moser C, Eron JJ, Currier JS, Klekotka P, Sette A, Wohl DA, Daar ES, Hughes MD, Chew KW, Smith DM, Crotty S; Accelerating COVID-19 Therapeutic Interventions and Vaccines–2/A5401 (ACTIV-2/A5401) Study Team. JCI Insight. 2022 Dec 22;7(24):e163471. doi: 10.1172/jci.insight.163471. PMID: 36378539 Free PMC article.
Comparison of test-negative and syndrome-negative controls in SARS-CoV-2 vaccine effectiveness evaluations for preventing COVID-19 hospitalizations in the United States. Turbyfill C, Adams K, Tenforde MW, Murray NL, Gaglani M, Ginde AA, McNeal T, Ghamande S, Douin DJ, Keipp Talbot H, Casey JD, Mohr NM, Zepeski A, Shapiro NI, Gibbs KW, Clark Files D, Hager DN, Shehu A, Prekker ME, Frosch AE, Exline MC, Gong MN, Mohamed A, Johnson NJ, Srinivasan V, Steingrub JS, Peltan ID, Brown SM, Martin ET, Lauring AS, Khan A, Busse LW, Ten Lohuis CC, Duggal A, Wilson JG, June Gordon A, Qadir N, Chang SY, Mallow C, Rivas C, Kwon JH, Halasa N, Chappell JD, Grijalva CG, Rice TW, Stubblefield WB, Baughman A, Rhoads JP, Lindsell CJ, Hart KW, McMorrow M, Surie D, Self WH, Patel MM. Vaccine. 2022 Nov 15;40(48):6979-6986. doi: 10.1016/j.vaccine.2022.10.034. Epub 2022 Oct 24. PMID: 36374708 Free PMC article.
Recurrence of Symptoms Following a 2-Day Symptom Free Period in Patients With COVID-19. Smith DM, Li JZ, Moser C, Yeh E, Currier JS, Chew KW, Hughes MD; ACTIV-2/A5401 Study Team.
JAMA Netw Open. 2022 Oct 3;5(10):e2238867. doi: 10.1001/jamanetworkopen.2022.38867. PMID: 36301549 Free PMC article.
Fluvoxamine for Outpatient Treatment of COVID-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial. McCarthy MW, Naggie S, Boulware DR, Lindsell CJ, Stewart TG, Felker GM, Jayaweera D, Sulkowski M, Gentile N, Bramante C, Singh U, Dolor RJ, Ruiz-Unger J, Wilson S, DeLong A, Remaly A, Wilder R, Collins S, Dunsmore SE, Adam SJ, Thicklin F, Hanna G, Ginde AA, Castro M, McTigue K, Shenkman E, Hernandez AF; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group. medRxiv. 2022 Nov 1:2022.10.17.22281178. doi: 10.1101/2022.10.17.22281178. Preprint. PMID: 36299427 Free PMC article.
Emergence of SARS-CoV-2 escape mutations during Bamlanivimab therapy in a phase II randomized clinical trial. Choudhary MC, Chew KW, Deo R, Flynn JP, Regan J, Crain CR, Moser C, Hughes MD, Ritz J, Ribeiro RM, Ke R, Dragavon JA, Javan AC, Nirula A, Klekotka P, Greninger AL, Fletcher CV, Daar ES, Wohl DA, Eron JJ, Currier JS, Parikh UM, Sieg SF, Perelson AS, Coombs RW, Smith DM, Li JZ; ACTIV-2/A5401 Study Team. Nat Microbiol. 2022 Nov;7(11):1906-1917. doi: 10.1038/s41564-022-01254-1. Epub 2022 Oct 26. PMID: 36289399 Clinical Trial.
Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial. Naggie S, Boulware DR, Lindsell CJ, Stewart TG, Gentile N, Collins S, McCarthy MW, Jayaweera D, Castro M, Sulkowski M, McTigue K, Thicklin F, Felker GM, Ginde AA, Bramante CT, Slandzicki AJ, Gabriel A, Shah NS, Lenert LA, Dunsmore SE, Adam SJ, DeLong A, Hanna G, Remaly A, Wilder R, Wilson S, Shenkman E, Hernandez AF; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) Study Group and Investigators. JAMA. 2022 Oct 25;328(16):1595-1603. doi: 10.1001/jama.2022.18590. PMID: 36269852 Clinical Trial.
Nasal and Plasma Severe Acute Respiratory Syndrome Coronavirus 2 RNA Levels Are Associated With Timing of Symptom Resolution in the ACTIV-2 Trial of Nonhospitalized Adults With Coronavirus Disease 2019. Li Y, Harrison LJ, Chew KW, Currier JS, Wohl DA, Daar ES, Evering TH, Wu R, Giganti M, Ritz J, Javan AC, Coombs RW, Moser C, Hughes MD, Eron JJ, Smith DM, Li JZ. Clin Infect Dis. 2023 Feb 18;76(4):734-737. doi: 10.1093/cid/ciac818. PMID: 36210483 Free PMC article. Clinical Trial.
Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19. Ko ER, Anstrom KJ, Panettieri RA, Lachiewicz AM, Maillo M, O'Halloran JA, Boucher C, Smith PB, McCarthy MW, Segura Nunez P, Mendivil Tuchia de Tai S, Khan A, Mena Lora AJ, Salathe M, Kedar E, Capo G, Rodríguez Gonzalez D, Patterson TF, Palma C, Ariza H, Patelli Lima M, Blamoun J, Nannini EC, Sprinz E, Mykietiuk A, Wang JP, Parra-Rodriguez L, Der T, Willsey K, Benjamin DK, Wen J, Zakroysky P, Halabi S, Silverstein A, McNulty SE, O'Brien SM, Al-Khalidi HR, Butler S, Atkinson J, Adam SJ, Chang S, Maldonado MA, Proscham M, LaVange L, Bozzette SA, Powderly WG; ACTIV-1 IM study group members. medRxiv. 2022 Sep 26:2022.09.22.22280247. doi: 10.1101/2022.09.22.22280247. Preprint. PMID: 36203544 Free PMC article.
The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19. ACTIV-3/TICO Study Group; Rogers AJ, Wentworth D, Phillips A, Shaw-Saliba K, Dewar RL, Aggarwal NR, Babiker AG, Chang W, Dharan NJ, Davey VJ, Higgs ES, Gerry N, Ginde AA, Hayanga JWA, Highbarger H, Highbarger JL, Jain MK, Kan V, Kim K, Lallemand P, Leshnower BG, Lutaakome JK, Matthews G, Mourad A, Mylonakis E, Natarajan V, Padilla ML, Pandit LM, Paredes R, Pett S, Ramachandruni S, Rehman MT, Sherman BT, Files DC, Brown SM, Matthay MA, Thompson BT, Neaton JD, Lane HC, Lundgren JD. Ann Intern Med. 2022 Oct;175(10):1401-1410. doi: 10.7326/M22-0924. Epub 2022 Aug 30. PMID: 36037469 Free PMC article.
Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults with COVID-19. Chew KW, Moser C, Daar ES, Wohl DA, Li JZ, Coombs RW, Ritz J, Giganti M, Javan AC, Li Y, Choudhary MC, Deo R, Malvestutto C, Klekotka P, Price K, Nirula A, Fischer W, Bala V, Ribeiro RM, Perelson AS, Fletcher CV, Eron JJ, Currier JS; ACTIV-2/A5401 Study Team; Hughes MD, Smith DM.
Nat Commun. 2022 Aug 22;13(1):4931. doi: 10.1038/s41467-022-32551-2. PMID: 35995785 Free PMC article. Clinical Trial.
Ivermectin for Treatment of Mild-to-Moderate COVID-19 in the Outpatient Setting: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial. Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group; Naggie S. medRxiv. 2022 Aug 11:2022.06.10.22276252. doi: 10.1101/2022.06.10.22276252. Preprint. PMID: 35982669 Free PMC article.
Viral and Symptom Rebound in Untreated COVID-19 Infection. Deo R, Choudhary MC, Moser C, Ritz J, Daar ES, Wohl DA, Greninger AL, Eron JJ, Currier JS, Hughes MD, Smith DM, Chew KW, Li JZ; ACTIV-2/A5401 Study Team. medRxiv. 2022 Aug 2:2022.08.01.22278278. doi: 10.1101/2022.08.01.22278278. Preprint. PMID: 35982660 Free PMC article.
Inhaled Fluticasone for Outpatient Treatment of Covid-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial. Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group; Naggie S. medRxiv. 2022 Aug 11:2022.07.12.22277548. doi: 10.1101/2022.07.12.22277548. Preprint.
PMID: 35982649 Free PMC article.
Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial. ACTIV-3/TICO Study Group; Barkauskas C, Mylonakis E, Poulakou G, Young BE, Vock DM, Siegel L, Engen N, Grandits G, Mosaly NR, Vekstein AM, Rogers R, Shehadeh F, Kaczynski M, Mylona EK, Syrigos KN, Rapti V, Lye DC, Hui DS, Leither L, Knowlton KU, Jain MK, Marines-Price R, Osuji A, Overcash JS, Kalomenidis I, Barmparessou Z, Waters M, Zepeda K, Chen P, Torbati S, Kiweewa F, Sebudde N, Almasri E, Hughes A, Bhagani SR, Rodger A, Sandkovsky U, Gottlieb RL, Nnakelu E, Trautner B, Menon V, Lutaakome J, Matthay M, Robinson P, Protopapas K, Koulouris N, Kimuli I, Baduashvili A, Braun DL, Günthard HF, Ramachandruni S, Kidega R, Kim K, Hatlen TJ, Phillips AN, Murray DD, Jensen TO, Padilla ML, Accardi EX, Shaw-Saliba K, Dewar RL, Teitelbaum M, Natarajan V, Laverdure S, Highbarger HC, Rehman MT, Vogel S, Vallée D, Crew P, Atri N, Schechner AJ, Pett S, Hudson F, Badrock J, Touloumi G, Brown SM, Self WH, North CM, Ginde AA, Chang CC, Kelleher A, Nagy-Agren S, Vasudeva S, Looney D, Nguyen HH, Sánchez A, Weintrob AC, Grund B, Sharma S, Reilly CS, Paredes R, Bednarska A, Gerry NP, Babiker AG, Davey VJ, Gelijns AC, Higgs ES, Kan V, Matthews G, Thompson BT, Legenne P, Chandra R, Lane HC, Neaton JD, Lundgren JD. Ann Intern Med. 2022 Sep;175(9):1266-1274. doi: 10.7326/M22-1503. Epub 2022 Aug 9. PMID: 35939810 Free PMC article. Clinical Trial.
Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. ACTIV-3–Therapeutics for Inpatients with COVID-19 (TICO) Study Group.
Lancet Respir Med. 2022 Oct;10(10):972-984. doi: 10.1016/S2213-2600(22)00215-6. Epub 2022 Jul 8. PMID: 35817072 Free PMC article. Clinical Trial.
Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection. Boucau J, Chew KW, Choudhary MC, Deo R, Regan J, Flynn JP, Crain CR, Hughes MD, Ritz J, Moser C, Dragavon JA, Javan AC, Nirula A, Klekotka P, Greninger AL, Coombs RW, Fischer WA 2nd, Daar ES, Wohl DA, Eron JJ, Currier JS, Smith DM; POSITIVES study team; Li JZ, Barczak AK; ACTIV-2/A5401 Study Team. Cell Rep Med. 2022 Jul 19;3(7):100678. doi: 10.1016/j.xcrm.2022.100678. Epub 2022 Jun 20. PMID: 35793677 Free PMC article. Clinical Trial.
Antithrombotic prophylaxis for symptomatic outpatients with COVID-19: less is consistently more. Connors JM, Ridker PM.
Lancet Haematol. 2022 Aug;9(8):e551-e553. doi: 10.1016/S2352-3026(22)00205-8. Epub 2022 Jun 30. PMID: 35779559 Free PMC article. No abstract available.
Rationale of using the dual chemokine receptor CCR2/CCR5 inhibitor cenicriviroc for the treatment of COVID-19. Files DC, Tacke F, O'Sullivan A, Dorr P, Ferguson WG, Powderly WG. PLoS Pathog. 2022 Jun 24;18(6):e1010547. doi: 10.1371/journal.ppat.1010547. eCollection 2022 Jun. PMID: 35749425 Free PMC article. Review.
Oxygen-Free Days as an Outcome Measure in Clinical Trials of Therapies for COVID-19 and Other Causes of New-Onset Hypoxemia. Moskowitz A, Shotwell MS, Gibbs KW, Harkins M, Rosenberg Y, Troendle J, Merck LH, Files DC, de Wit M, Hudock K, Thompson BT, Gong MN, Ginde AA, Douin DJ, Brown SM, Rubin E, Joly MM, Wang L, Lindsell CJ, Bernard GR, Semler MW, Collins SP, Self WH; Fourth Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4) Host Tissue Investigators. Chest. 2022 Oct;162(4):804-814. doi: 10.1016/j.chest.2022.04.145. Epub 2022 Apr 30. PMID: 35504307 Free PMC article. Review.
Clinical predictors of COVID-19 severity and bleeding in the ACTIV-4B COVID-19 outpatient thrombosis prevention trial. Connors JM, Brooks MM, Sciurba FC, Fu Z, Ridker PM. Am J Hematol. 2022 Jul;97(7):E235-E240. doi: 10.1002/ajh.26553. Epub 2022 Apr 11.
PMID: 35358342 Free PMC article.
RAGE has potential pathogenetic and prognostic value in nonintubated hospitalized patients with COVID-19. Wick KD, Siegel L, Neaton JD, Oldmixon C, Lundgren J, Dewar RL, Lane HC, Thompson BT, Matthay MA; ACTIV-3/TICO study group. JCI Insight. 2022 May 9;7(9):e157499. doi: 10.1172/jci.insight.157499. PMID: 35298440 Free PMC article. Clinical Trial.
Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial. Berger JS, Kornblith LZ, Gong MN, Reynolds HR, Cushman M, Cheng Y, McVerry BJ, Kim KS, Lopes RD, Atassi B, Berry S, Bochicchio G, de Oliveira Antunes M, Farkouh ME, Greenstein Y, Hade EM, Hudock K, Hyzy R, Khatri P, Kindzelski A, Kirwan BA, Baumann Kreuziger L, Lawler PR, Leifer E, Lopez-Sendon Moreno J, Lopez-Sendon J, Luther JF, Nigro Maia L, Quigley J, Sherwin R, Wahid L, Wilson J, Hochman JS, Neal MD; ACTIV-4a Investigators.
JAMA. 2022 Jan 18;327(3):227-236. doi: 10.1001/jama.2021.23605.
PMID: 35040887 Free PMC article. Clinical Trial.
Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection. Boucau J, Chew KW, Choudhary M, Deo R, Regan J, Flynn JP, Crain CR, Hughes MD, Ritz J, Moser C, Dragavon JA, Javan AC, Nirula A, Klekotka P, Greninger AL, Coombs RW, Fischer WA 2nd, Daar ES, Wohl DA, Eron JJ, Currier JS, Smith DM, Li JZ, Barczak AK; ACTIV-2/A5401 Study Team. medRxiv. 2021 Dec 30:2021.12.25.21268211. doi: 10.1101/2021.12.25.21268211. Preprint. PMID: 35018382 Free PMC article. Updated.
Bamlanivimab reduces nasopharyngeal SARS-CoV-2 RNA levels but not symptom duration in non-hospitalized adults with COVID-19. Chew KW, Moser C, Daar ES, Wohl DA, Li JZ, Coombs R, Ritz J, Giganti M, Javan AC, Li Y, Malvestutto C, Klekotka P, Price K, Nirula A, Fischer W, Bala V, Ribeiro RM, Perelson AS, Fletcher CV, Eron JJ, Currier JS, Hughes MD, Smith DM. medRxiv. 2021 Dec 21:2021.12.17.21268009. doi: 10.1101/2021.12.17.21268009. Preprint. PMID: 34981077 Free PMC article.
Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial. ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Lancet Infect Dis. 2022 May;22(5):622-635. doi: 10.1016/S1473-3099(21)00751-9. Epub 2021 Dec 23. PMID: 34953520 Free PMC article. Clinical Trial.
Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial. ACTIV-3/TICO Bamlanivimab Study Group; Lundgren JD, Grund B, Barkauskas CE, Holland TL, Gottlieb RL, Sandkovsky U, Brown SM, Knowlton KU, Self WH, Files DC, Jain MK, Benfield T, Bowdish ME, Leshnower BG, Baker JV, Jensen JU, Gardner EM, Ginde AA, Harris ES, Johansen IS, Markowitz N, Matthay MA, Østergaard L, Chang CC, Goodman AL, Chang W, Dewar RL, Gerry NP, Higgs ES, Highbarger H, Murray DD, Murray TA, Natarajan V, Paredes R, Parmar MKB, Phillips AN, Reilly C, Rupert AW, Sharma S, Shaw-Saliba K, Sherman BT, Teitelbaum M, Wentworth D, Cao H, Klekotka P, Babiker AG, Davey VJ, Gelijns AC, Kan VL, Polizzotto MN, Thompson BT, Lane HC, Neaton JD.
Ann Intern Med. 2022 Feb;175(2):234-243. doi: 10.7326/M21-3507. Epub 2021 Dec 21. PMID: 34928698 Free PMC article. Clinical Trial.
Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial. Connors JM, Brooks MM, Sciurba FC, Krishnan JA, Bledsoe JR, Kindzelski A, Baucom AL, Kirwan BA, Eng H, Martin D, Zaharris E, Everett B, Castro L, Shapiro NL, Lin JY, Hou PC, Pepine CJ, Handberg E, Haight DO, Wilson JW, Majercik S, Fu Z, Zhong Y, Venugopal V, Beach S, Wisniewski S, Ridker PM; ACTIV-4B Investigators. JAMA. 2021 Nov 2;326(17):1703-1712. doi: 10.1001/jama.2021.17272. PMID: 34633405 Free PMC article. Clinical Trial.
Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3). Murray DD, Babiker AG, Baker JV, Barkauskas CE, Brown SM, Chang CC, Davey VJ, Gelijns AC, Ginde AA, Grund B, Higgs E, Hudson F, Kan VL, Lane HC, Murray TA, Paredes R, Parmar MK, Pett S, Phillips AN, Polizzotto MN, Reilly C, Sandkovsky U, Sharma S, Teitelbaum M, Thompson BT, Young BE, Neaton JD, Lundgren JD.
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Emergence of SARS-CoV-2 Resistance with Monoclonal Antibody Therapy. Choudhary MC, Chew KW, Deo R, Flynn JP, Regan J, Crain CR, Moser C, Hughes M, Ritz J, Ribeiro RM, Ke R, Dragavon JA, Javan AC, Nirula A, Klekotka P, Greninger AL, Fletcher CV, Daar ES, Wohl DA, Eron JJ, Currier JS, Parikh UM, Sieg SF, Perelson AS, Coombs RW, Smith DM, Li JZ; ACTIV-2/A5401 Study Team. medRxiv. 2021 Sep 15:2021.09.03.21263105. doi: 10.1101/2021.09.03.21263105. Preprint. PMID: 34545376 Free PMC article.
Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines-Selecting Compounds for Clinical Evaluation in Coronavirus Disease 2019 Clinical Trials. Buchman TG, Draghia-Akli R, Adam SJ, Aggarwal NR, Fessel JP, Higgs ES, Menetski JP, Read SW, Hughes EA; Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines (ACTIV) Therapeutics Clinical Working Group. Crit Care Med. 2021 Nov 1;49(11):1963-1973. doi: 10.1097/CCM.0000000000005295. PMID: 34495876 Free PMC article. Review.
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Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators; Lawler PR, Goligher EC, Berger JS, Neal MD, McVerry BJ, Nicolau JC, Gong MN, Carrier M, Rosenson RS, Reynolds HR, Turgeon AF, Escobedo J, Huang DT, Bradbury CA, Houston BL, Kornblith LZ, Kumar A, Kahn SR, Cushman M, McQuilten Z, Slutsky AS, Kim KS, Gordon AC, Kirwan BA, Brooks MM, Higgins AM, Lewis RJ, Lorenzi E, Berry SM, Berry LR, Aday AW, Al-Beidh F, Annane D, Arabi YM, Aryal D, Baumann Kreuziger L, Beane A, Bhimani Z, Bihari S, Billett HH, Bond L, Bonten M, Brunkhorst F, Buxton M, Buzgau A, Castellucci LA, Chekuri S, Chen JT, Cheng AC, Chkhikvadze T, Coiffard B, Costantini TW, de Brouwer S, Derde LPG, Detry MA, Duggal A, Džavík V, Effron MB, Estcourt LJ, Everett BM, Fergusson DA, Fitzgerald M, Fowler RA, Galanaud JP, Galen BT, Gandotra S, García-Madrona S, Girard TD, Godoy LC, Goodman AL, Goossens H, Green C, Greenstein YY, Gross PL, Hamburg NM, Haniffa R, Hanna G, Hanna N, Hegde SM, Hendrickson CM, Hite RD, Hindenburg AA, Hope AA, Horowitz JM, Horvat CM, Hudock K, Hunt BJ, Husain M, Hyzy RC, Iyer VN, Jacobson JR, Jayakumar D, Keller NM, Khan A, Kim Y, Kindzelski AL, King AJ, Knudson MM, Kornblith AE, Krishnan V, Kutcher ME, Laffan MA, Lamontagne F, Le Gal G, Leeper CM, Leifer ES, Lim G, Lima FG, Linstrum K, Litton E, Lopez-Sendon J, Lopez-Sendon Moreno JL, Lother SA, Malhotra S, Marcos M, Saud Marinez A, Marshall JC, Marten N, Matthay MA, McAuley DF, McDonald EG, McGlothlin A, McGuinness SP, Middeldorp S, Montgomery SK, Moore SC, Morillo Guerrero R, Mouncey PR, Murthy S, Nair GB, Nair R, Nichol AD, Nunez-Garcia B, Pandey A, Park PK, Parke RL, Parker JC, Parnia S, Paul JD, Pérez González YS, Pompilio M, Prekker ME, Quigley JG, Rost NS, Rowan K, Santos FO, Santos M, Olombrada Santos M, Satterwhite L, Saunders CT, Schutgens REG, Seymour CW, Siegal DM, Silva DG Jr, Shankar-Hari M, Sheehan JP, Singhal AB, Solvason D, Stanworth SJ, Tritschler T, Turner AM, van Bentum-Puijk W, van de Veerdonk FL, van Diepen S, Vazquez-Grande G, Wahid L, Wareham V, Wells BJ, Widmer RJ, Wilson JG, Yuriditsky E, Zampieri FG, Angus DC, McArthur CJ, Webb SA, Farkouh ME, Hochman JS, Zarychanski R. N Engl J Med. 2021 Aug 26;385(9):790-802. doi: 10.1056/NEJMoa2105911. Epub 2021 Aug 4. PMID: 34351721 Free PMC article. Clinical Trial.
COVID-19: Thrombosis, thromboinflammation, and anticoagulation considerations. Levy JH, Iba T, Olson LB, Corey KM, Ghadimi K, Connors JM. Int J Lab Hematol. 2021 Jul;43 Suppl 1(Suppl 1):29-35. doi: 10.1111/ijlh.13500. PMID: 34288441 Free PMC article. Review.
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV): Designing Master Protocols for Evaluation of Candidate COVID-19 Therapeutics. LaVange L, Adam SJ, Currier JS, Higgs ES, Reineck LA, Hughes EA, Read SW; ACTIV Therapeutics-Clinical Working Group. Ann Intern Med. 2021 Sep;174(9):1293-1300. doi: 10.7326/M21-1269. Epub 2021 Jun 29. PMID: 34181444 Free PMC article.
A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19. ACTIV-3/TICO LY-CoV555 Study Group; Lundgren JD, Grund B, Barkauskas CE, Holland TL, Gottlieb RL, Sandkovsky U, Brown SM, Knowlton KU, Self WH, Files DC, Jain MK, Benfield T, Bowdish ME, Leshnower BG, Baker JV, Jensen JU, Gardner EM, Ginde AA, Harris ES, Johansen IS, Markowitz N, Matthay MA, Østergaard L, Chang CC, Davey VJ, Goodman A, Higgs ES, Murray DD, Murray TA, Paredes R, Parmar MKB, Phillips AN, Reilly C, Sharma S, Dewar RL, Teitelbaum M, Wentworth D, Cao H, Klekotka P, Babiker AG, Gelijns AC, Kan VL, Polizzotto MN, Thompson BT, Lane HC, Neaton JD. N Engl J Med. 2021 Mar 11;384(10):905-914. doi: 10.1056/NEJMoa2033130. Epub 2020 Dec 22. PMID: 33356051 Free PMC article. Clinical Trial.
Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3). Murray DD, Babiker AG, Baker JV, Barkauskas CE, Brown SM, Chang CC, Davey VJ, Gelijns AC, Ginde AA, Grund B, Higgs E, Hudson F, Kan VL, Lane HC, Murray TA, Paredes R, Parmar MKB, Pett S, Phillips AN, Polizzotto MN, Reilly C, Sandkovsky U, Sharma S, Teitelbaum M, Thompson BT, Young BE, Neaton JD, Lundgren JD. medRxiv. 2021 Apr 8:2020.11.08.20227876. doi: 10.1101/2020.11.08.20227876. Preprint. PMID: 33215168 Free PMC article. Updated.