PMID- 26644172

OWN - NLM
STAT- MEDLINE
DCOM- 20160301
LR - 20160714
IS - 1533-4406 (Electronic)
IS - 0028-4793 (Linking)
VI - 374
IP - 7
DP - 2016 Feb 18
TI - A Multinational Trial of Prasugrel for Sickle Cell Vaso-Occlusive Events.
PG - 625-35
LID - 10.1056/NEJMoa1512021 [doi]
AB - BACKGROUND: Sickle cell anemia is an inherited blood disorder that is
characterized by painful vaso-occlusive crises, for which there are few
treatment
options. Platelets mediate intercellular adhesion and thrombosis during
vaso-occlusion in sickle cell anemia, which suggests a role for antiplatelet
agents in modifying disease events. METHODS: Children and adolescents 2
through
17 years of age with sickle cell anemia were randomly assigned to receive
oral
prasugrel or placebo for 9 to 24 months. The primary end point was the rate
of
vaso-occlusive crisis, a composite of painful crisis or acute chest syndrome.
The
secondary end points were the rate of sickle cell-related pain and the
intensity
of pain, which were assessed daily with the use of pain diaries. RESULTS: A
total
of 341 patients underwent randomization at 51 sites in 13 countries across
the
Americas, Europe, Asia, and Africa. The rate of vaso-occlusive crisis events
per
person-year was 2.30 in the prasugrel group and 2.77 in the placebo group
(rate
ratio, 0.83; 95% confidence interval, 0.66 to 1.05; P=0.12). There were no
significant differences between the groups in the secondary end points of
diary-reported events. The safety end points, including the frequency of
bleeding
events requiring medical intervention, of hemorrhagic and nonhemorrhagic
adverse
events that occurred while patients were taking prasugrel or placebo, and of
discontinuations due to prasugrel or placebo, did not differ significantly
between the groups. CONCLUSIONS: Among children and adolescents with sickle
cell
anemia, the rate of vaso-occlusive crisis was not significantly lower among
those
who received prasugrel than among those who received placebo. There were no
significant between-group differences in the safety findings. (Funded by
Daiichi
Sankyo and Eli Lilly; ClinicalTrials.gov number, NCT01794000.).
FAU - Heeney, Matthew M
AU - Heeney MM
AD - From the Dana-Farber/Boston Children's Cancer and Blood Disorders Center,
Boston
(M.M.H.); UCSF Benioff Children's Hospital Oakland, Oakland, CA (C.C.H.); the
Department of Pediatrics and Adolescent Medicine, American University of
Beirut,
Beirut, Lebanon (M.R.A.); Evelina Children's Hospital (B.I.), Guy's and St.
Thomas' Hospital (B.I.), Daiichi Sankyo Development (D.Z.), and King's
College
Hospital, Denmark Hill (D.C.R.) - all in London; the Department of
Pediatrics,
Division of Pediatric Hematology-Oncology, Medical University of South
Carolina,
Charleston (J.K.); U.S. Army Medical Research Unit-Kenya, Malaria Resistance
(B.O.), Kenya Medical Research Institute-Walter Reed Project (J.N.O.), and
the
Center for Global Health Research and Public Health Collaboration (V.N.N.),
Kenya
Medical Research Institute - all in Kisumu, Kenya; Eli Lilly, Indianapolis
(P.B.B., L.E.H., J.A.J., C.Z.); Kwame Nkrumah University of Science and
Technology, Kumasi (T.A.), and the Department of Child Health, School of
Medicine
and Dentistry, Korle Bu Teaching Hospital, Accra (C.I.S.) - both in Ghana;
the
Clinic of Pediatric Hematology-Oncology, Azienda Ospedaliera-University of
Padua,
Padua, Italy (R.C.); Clinical Research Center, Alexandria University,
Alexandria,
Egypt (H.M.H.); and the Department of Pediatrics, Division of
Hematology-Oncology, Centre Hospitalier Universitaire Sainte-Justine,
Montreal
(N.R.).
FAU - Hoppe, Carolyn C
AU - Hoppe CC
FAU - Abboud, Miguel R
AU - Abboud MR
FAU - Inusa, Baba
AU - Inusa B
FAU - Kanter, Julie
AU - Kanter J
FAU - Ogutu, Bernhards
AU - Ogutu B
FAU - Brown, Patricia B
AU - Brown PB
FAU - Heath, Lori E
AU - Heath LE
FAU - Jakubowski, Joseph A
AU - Jakubowski JA
FAU - Zhou, Chunmei
AU - Zhou C
FAU - Zamoryakhin, Dmitry
AU - Zamoryakhin D
FAU - Agbenyega, Tsiri
AU - Agbenyega T
FAU - Colombatti, Raffaella
AU - Colombatti R
FAU - Hassab, Hoda M
AU - Hassab HM
FAU - Nduba, Videlis N
AU - Nduba VN
FAU - Oyieko, Janet N
AU - Oyieko JN
FAU - Robitaille, Nancy
AU - Robitaille N
FAU - Segbefia, Catherine I
AU - Segbefia CI
FAU - Rees, David C
AU - Rees DC
CN - DOVE Investigators
LA - eng
SI - ClinicalTrials.gov/NCT01794000
PT - Clinical Trial, Phase III
PT - Journal Article
PT - Multicenter Study
PT - Randomized Controlled Trial
PT - Research Support, Non-U.S. Gov't
DEP - 20151208
PL - United States
TA - N Engl J Med
JT - The New England journal of medicine
JID - 0255562
RN - 0 (Platelet Aggregation Inhibitors)
RN - G89JQ59I13 (Prasugrel Hydrochloride)
SB - AIM
SB - IM
CIN - N Engl J Med. 2016 Jul 14;375(2):185-6. PMID: 27410930
CIN - N Engl J Med. 2016 Jul 14;375(2):185. PMID: 27410931
MH - Acute Chest Syndrome/etiology/*prevention & control
MH - Administration, Oral
MH - Adolescent
MH - Anemia, Sickle Cell/complications/*drug therapy
MH - Child
MH - Child, Preschool
MH - Double-Blind Method
MH - Female
MH - Hemorrhage/chemically induced
MH - Humans
MH - Male
MH - Pain/etiology/*prevention & control
MH - Peripheral Vascular Diseases/etiology/prevention & control
MH - Platelet Aggregation Inhibitors/adverse effects/*therapeutic use
MH - Prasugrel Hydrochloride/adverse effects/*therapeutic use
IR - Van Damme A
FIR - Van Damme, An
IR - Dupont S
FIR - Dupont, Sophie
IR - Philippet P
FIR - Philippet, Pierre
IR - Lobo CL
FIR - Lobo, Clarisse Lopes de Castro
IR - Robitaille N
FIR - Robitaille, Nancy
IR - Tantawy AA
FIR - Tantawy, Azza A G
IR - Mansour AK
FIR - Mansour, Ahmed K
IR - Al-Tonbary Y
FIR - Al-Tonbary, Youssef
IR - Badr M
FIR - Badr, Mohamed
IR - Elgawhary S
FIR - Elgawhary, Somaya
IR - Ragab L
FIR - Ragab, Lamis
IR - Hassab H
FIR - Hassab, Hoda
IR - El-Sayed HA
FIR - El-Sayed, Hesham A F Mohamed
IR - Agbenyega E
FIR - Agbenyega, E Tsiri
IR - Segbefia CI
FIR - Segbefia, Catherine I
IR - Colombatti R
FIR - Colombatti, Raffaella
IR - Forni GL
FIR - Forni, Gian L
IR - Masera N
FIR - Masera, Nicoletta
IR - Palazzi G
FIR - Palazzi, Giovanni
IR - Cesaro S
FIR - Cesaro, Simone
IR - Ogutu BR
FIR - Ogutu, Bernhards R
IR - Oyieko JN
FIR - Oyieko, Janet N
IR - Nduba V
FIR - Nduba, Videlis
IR - Githanga JN
FIR - Githanga, Jessie N
IR - Abboud MR
FIR - Abboud, Miguel R
IR - Inati A
FIR - Inati, Adlette
IR - Alkindi SS
FIR - Alkindi, Salam S
IR - Al Jaouni SK
FIR - Al Jaouni, Soad K
IR - Unal S
FIR - Unal, Selma
IR - Sasmaz I
FIR - Sasmaz, Ilgen
IR - Antmen AB
FIR - Antmen, Ali B
IR - Alzoebie A
FIR - Alzoebie, Azzam
IR - Inusa B
FIR - Inusa, Baba
IR - Rees D
FIR - Rees, David
IR - Will A
FIR - Will, Andrew
IR - Dampier C
FIR - Dampier, Carlton
IR - Heeney MM
FIR - Heeney, Matthew M
IR - Irwin RG
FIR - Irwin, Robert G
IR - Cohen D
FIR - Cohen, Debra
IR - Quinn CT
FIR - Quinn, Charles T
IR - Krishnamurti L
FIR - Krishnamurti, Lakshmanan
IR - Rana S
FIR - Rana, Sohail
IR - Sarnaik SA
FIR - Sarnaik, Sharada A
IR - Smith-Whitley K
FIR - Smith-Whitley, Kim
IR - Hoppe C
FIR - Hoppe, Carolyn
IR - Thompson AA
FIR - Thompson, Alexis A
IR - Boruchov DM
FIR - Boruchov, Donna M
IR - Estepp JH
FIR - Estepp, Jeremie Heath
IR - Redding-Lallinger R
FIR - Redding-Lallinger, Rupa
IR - Strunk C
FIR - Strunk, Crawford
IR - Piccone C
FIR - Piccone, Connie
IR - Jeng M
FIR - Jeng, Michael
IR - Whittle J
FIR - Whittle, John
IR - Eng J
FIR - Eng, Jennifer
IR - Manwani D
FIR - Manwani, Deepa
IR - Woods G
FIR - Woods, Gerald
IR - Kanter J
FIR - Kanter, Julie
EDAT- 2015/12/09 06:00
MHDA- 2016/03/02 06:00
CRDT- 2015/12/09 06:00
PHST- 2015/12/09 06:00 [entrez]
PHST- 2015/12/09 06:00 [pubmed]
PHST- 2016/03/02 06:00 [medline]
AID - 10.1056/NEJMoa1512021 [doi]
PST - ppublish
SO - N Engl J Med. 2016 Feb 18;374(7):625-35. doi: 10.1056/NEJMoa1512021. Epub
2015
Dec 8.