A randomized, controlled trial of Ebola virus disease therapeutics

New England Journal of Medicine

Volumn 381, Issue 24, 2019, Pages 2293-2303

  Mulangu, Sabue ^a   Dodd, Lori E ^b   Davey, Richard T ^b   Mbaya, Olivier Tshiani ^a   Proschan, Michael ^b   Mukadi, Daniel ^a   Manzo, Mariano Lusakibanza ^a   Nzolo, Didier ^a   Oloma, Antoine Tshomba ^a   Ibanda, Augustin ^a   Ali, Rosine ^a   Coulibaly, Sinaré ^c   Levine, Adam C ^d   Grais, Rebecca ^e   Diaz, Janet ^f   Clifford Lane, H ^b   Muyembe Tamfum, Jean Jacques ^a   Sivahera, Billy ^c   Camara, Modet ^c   Kojan, Richard ^c   Walker, Robert ^g   Dighero Kemp, Bonnie ^h   Cao, Huyen ⁱ   Mukumbayi, Philippe ^a   Mbala Kingebeni, Placide ^a   Ahuka, Steve ^a   Albert, Sarah ^j   Bonnett, Tyler ^j   Crozier, Ian ^j   Duvenhage, Michael ^j   Proffitt, Calvin ^j   Teitelbaum, Marc ^j   Moench, Thomas ^k   Aboulhab, Jamila ^b   Barrett, Kevin ^b   Cahill, Kelly ^b   Cone, Katherine ^b   Eckes, Risa ^b   Hensley, Lisa ^b   Herpin, Betsey ^b   Higgs, Elizabeth ^b   Ledgerwood, Julie ^b   Pierson, Jerome ^b   Smolskis, Mary ^b   Sow, Ydrissa ^b   Tierney, John ^b   Sivapalasingam, Sumathi ^l   Holman, Wendy ^m   Gettinger, Nikki ⁿ   Vallée, David ⁿ   Nordwall, Jacqueline ^o   more..

^a Institut National de Recherche Biomedicale   (Congo)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^c Alliance for International Medical Action   (Senegal)

^d INTERNATIONAL MEDICAL CORPS   (United States)

^e MÉDECINS SANS FRONTIÈRES   (Switzerland)

^f WORLD HEALTH ORGANIZATION   (Switzerland)

^g Biomedical Advanced Research and Development Authority

^h BATTELLE MEMORIAL INSTITUTE   (United States)

ⁱ Gilead   (United States)

^j FREDERICK NATIONAL LABORATORY FOR CANCER RESEARCH   (United States)

^k Mapp Biopharmaceutical   (United States)

^l Regeneron ^*  (United States)

^m Ridgeback Biotherapeutics ^*

ⁿ Mitchell Group   (Canada)

^o UNIVERSITY OF MINNESOTA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

AMINOTRANSFERASE; ANTIVIRUS AGENT; CREATININE; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY MAB114; MONOCLONAL ANTIBODY REGN EB3; MONOCLONAL ANTIBODY ZMAPP; REMDESIVIR; UNCLASSIFIED DRUG; VIRUS RNA; ALANINE; GS-5734; RIBONUCLEOTIDE; ZMAPP;

ADOLESCENT; ADULT; AMINOTRANSFERASE BLOOD LEVEL; ANALYSIS; ARTICLE; CHILD; CONGO; CONTROLLED STUDY; CORRELATION ANALYSIS; CREATININE BLOOD LEVEL; DEATH; DISEASE DURATION; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG WITHDRAWAL; EBOLA HEMORRHAGIC FEVER; FEMALE; GASTROINTESTINAL SYMPTOM; HEART ARREST; HOSPITAL ADMISSION; HUMAN; HYPOTENSION; HYPOXIA; INTERIM ANALYSIS; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MORTALITY; NONHUMAN; PATIENT MONITORING; PRESCHOOL CHILD; PRIORITY JOURNAL; PROGNOSIS; RANDOMIZED CONTROLLED TRIAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SCHOOL CHILD; SINGLE DRUG DOSE; SURVIVAL; VIRUS LOAD; YOUNG ADULT; BLOOD; CLINICAL TRIAL; COMPARATIVE STUDY; DEMOCRATIC REPUBLIC CONGO; EBOLAVIRUS; EPIDEMIC; EPIDEMIOLOGY; GENETICS; INFANT; INTRAVENOUS DRUG ADMINISTRATION; MULTICENTER STUDY; NEWBORN; SINGLE BLIND PROCEDURE;

ADOLESCENT; ADULT; ALANINE; ANTIBODIES, MONOCLONAL; ANTIVIRAL AGENTS; CHILD; CHILD, PRESCHOOL; DEMOCRATIC REPUBLIC OF THE CONGO; DISEASE OUTBREAKS; EBOLAVIRUS; FEMALE; HEMORRHAGIC FEVER, EBOLA; HUMANS; INFANT; INFANT, NEWBORN; INFUSIONS, INTRAVENOUS; MALE; RIBONUCLEOTIDES; RNA, VIRAL; SINGLE-BLIND METHOD; YOUNG ADULT;

EID: 85076449492     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1910993     Document Type: Article

References (18)

1. Ebola situation reports: Democratic Republic of the Congo (archive). Geneva: World Health Organization (https://www.who.int/ebola/situation-reports/drc-2018/en/).
2. Ebola virus disease — Democratic Republic of the Congo. Geneva: World Health Organization, September 19, 2019 (https://www.who.int/csr/don/19-september-2019-ebola-drc/en/).
3. Ebola/Marburg research and development (R&D) roadmap. Geneva: World Health Organization, May 2018 (https://www.who.int/blueprint/priority-diseases/key-action/Ebola-Marburg_Draft_Roadmap_publiccomment_MAY2018.pdf?ua=1).
4. Dodd LE, Follmann D, Proschan M, et al. On the importance of randomized controlled trials for Ebola virus disease therapeutics: a meta-analysis from the West African outbreak. Sci Transl Med (in press).
5. Qiu X, Wong G, Audet J, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 2014;514:47-53.
6. Warren TK, Jordan R, Lo MK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 2016;531:381-5.
7. Corti D, Misasi J, Mulangu S, et al. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science 2016;351:1339-42.
8. Gaudinski MR, Coates EE, Novik L, et al. Safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mAb114 targeting Ebola virus glycoprotein (VRC 608): an open-label phase 1 study. Lancet 2019; 393:889-98.
9. Pascal KE, Dudgeon D, Trefry JC, et al. Development of clinical-stage human monoclonal antibodies that treat advanced Ebola virus disease in nonhuman primates. J Infect Dis 2018;218:Suppl_5:S612-S626.
10. Sivapalasingam S, Kamal M, Slim R, et al. Safety, pharmacokinetics, and immunogenicity of a co-formulated cocktail of three human monoclonal antibodies targeting Ebola virus glycoprotein in healthy adults: a randomised, first-in-human phase 1 study. Lancet Infect Dis 2018;18:884-93.
11. The PREVAIL II Writing Group for the Multi-National PREVAIL II Study Team. A randomized, controlled trial of ZMapp for Ebola virus infection. N Engl J Med 2016; 375:1448-56.
12. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims. Silver Spring, MD: Food and Drug Administration, December 2009 (https://www.fda.gov/media/77832/download).
13. Xpert Ebola assay. Solna, Sweden: Cepheid, March 2015 (https://www.fda.gov/media/91944/download).
14. Mbala-Kingebeni P, Aziza A, Di Paola N, et al. Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo: a rapid genomic assessment. Lancet Infect Dis 2019;19:648-57.
15. Fay MP, Proschan MA, Brittain E. Combining one-sample confidence procedures for inference in the two-sample case. Biometrics 2015;71:146-56.
16. Proschan MA, Dodd LE, Price D. Statistical considerations for a trial of Ebola virus disease therapeutics. Clin Trials 2016; 13:39-48.
17. Rollin PE, Bausch DG, Sanchez A. Blood chemistry measurements and D-dimer levels associated with fatal and nonfatal outcomes in humans infected with Sudan Ebola virus. J Infect Dis 2007;196: Suppl 2:S364-S371.
18. Connor MJ Jr, Kraft C, Mehta AK, et al. Successful delivery of RRT in Ebola virus disease. J Am Soc Nephrol 2015;26:31-7.