Clopidogrel in infants with systemic-to-pulmonary-artery shunts.

Wessel, David L; Berger, Felix; Li, Jennifer S; Dähnert, Ingo; Rakhit, Amit; Fontecave, Sylvie; Newburger, Jane W; CLARINET Investigators; Trentadue, Julio; Gutierrez, Diego; Antoni, Diego; Toledo, Ruben; Parodi, Willy Conejeros; Guerrero, Rafael; Klinger, Daniel; Magliola, Ricardo; Mazzucchelli, Maria Teresa; Moreno, Mariano; Bellani, Patricia; Couceiro, Claudia; Marantz, Pablo; Rosselot, Silvina; Benmaor, Lisandro; Elorriaga, Maria Sol; Peña, Gabriela; Somoza, Felipe; Romero, Sandra; Barrea, Catherine; Sluysmans, Thierry; Nimbona, Grégoire; Senga, John; Moniotte, Stephane; Dessy, Hughes; Massin, Martial; Milani, Sophie Malekzadeh; Mertens, Luc; Gewillig, Marc; Boshoff, Derize; Eyskens, Bénédicte; De Wolf, Daniel; De Grote, Katia; Panzer, Joseph; Santana, Maria Virginia Tavares; Miaiara, Marly Akiko; Santin, Julio; Pontes, Sergio C; Guerra, Ana Luiza Paulista; Dona, Taciana C; Paulista, Paulo Paredes; Souza, Luiz Carlos; Chaccur, Paulo; Pedra, Carlos Augusto; Daudt, Nestor Santos; Horowitz, Estela; Kozak, Marcelo Felipe; Kozak, Ana Carolina Leiroz Ferreira Botelho Maisano; Croti, Ulisses Alexandre; Caneo, Luis Fernando; Afiune, Jorge; Succi, Fabiana Menezes Passos; Hincapie, Mauricio Jaramilllo; Afiune, Cristina Machado Camargo; Diniz, Juliana Duarte; de Faria, Gladis Aparecida; Pilla, Carlo Benatti; Blacher, Celso; Botta, Aline Medeiros; Pereira, Carla Abrahão; Luiz, Raquel Osorio; Mulinari, Leonardo Andrade; Navarro, Fabio; Pimentel, Gustavo Klug; Miyague, Nelson; Binotto, Cristiane; Pelissari, Eliana C; Sandrini, Marilise K; Lenzi, Andrea; Maluf, Miguel Angel; Diógenes, Suely; Carvalho, Antonio Carlos; Stocco, Jose Cicero; Silva, Celia Maria; Piante, Luana Salvoni; Pereira, Christian Santos; Trigueiro, Augusto; Pasqualucci, Patricia; Human, Derek; Potts, Jim; Kakadekar, Ashok; Koravangattu, Sankaran; Chetaille, Philippe; Cote, Jean-Marc; Houde, Christine; Delisle, Georges; Jia, Bing; Zhu, Bingxue; Pan, Yun; Li, Shoujun; Lv, Xiaodong; Luo, Yi; Zhang, Hui; Zhuang, Jian; Zeng, Rong; Lei, Liming; Shi, Chengren; Xie, Wei; Wang, Jou-Kou; Wu, Mei-Hwan; Hsieh, Kai-Sheng; Lu, Wen-Hsien; Sondergaard, Lars; Reimers, Jesper; Helvind, Morten; Shoeb, Mohamed Ayman; Desoky, Ahmed; El Sayed, Maiy Hamdy; Moftah, Hassan Mohamed; Tynkkynen, Paula; Sairanen, Heikki; Rautiainen, Paula; Turanlahti, Maila; Mildh, Leena; Fraisse, Alain; Blanc, Julie; Metras, Dominique; Ghez, Olivier; Bonello, Béatrice; Fouilloux, Virginie; Paoli, Florent; Chantepie, Alain; Poinsot, Jacques; Neuville, Paul; Vaillant, Marie-Catherine; Bergoend, Eric; Michel-Behnke, Ina; Billinger, Kai; Berger, Felix; Hacke, Paul; Ewert, Peter; Abedini, Mojtaba; Kanaan, Majed; Yilmaz, Sevim; Paul, Thomas; Gravenhorst, Verena; Dann, Gisela; Kramer, Hans-Heiner; Hoffmann, Ulrike; Reineker, Katja; Entenmann, Andreas; Fischer, Gunther; Jung, Olaf; Dähnert, Ingo; Wörner, Cornelia; Suchowerskyj, Philipp; Uhlemann, Frank; Leischner, Klaus; Pross, Lutz; Kececioglu, Deniz; Schaeffler, Rainer; Kleideiter, Ulrich; Fischer, Marcus; Kozlik-Feldmann, Rainer; Roemer, Ulrich; Lang, Nora; Nuebel, Julia; Hess, John; Balling, Gunther; de Winkel, Nicole; Cheung, Yiu-Fai; Cheung, Eddie Wai-Yin; Cheng, Lik-Cheung; Chau, Adolphus K T; Szatmari, Andras; Ladanyi, Aniko; Rao, Nitin; Mannam, Gopichand; Vyas, Suman; Karmalkar, Mukund; Manohar, Krishna; Dharan, Baiju S; Sadiq, Adil; Koneti, Nageswara Rao; Swain, Sunil; Murthy, Kona Samba; Koshy, Sajan; Anil, S R; Kurup, Renu; Ranjit, Madathil; Kamath, Shrishu; Gandhi, Deepika; Vanaki, Raghavendra; Kural, Vijay; Grover, Vijay; Gupta, Vijay; Agarwal, Ravi; Sekar, R Prem; Roy, Christopher; Rao, Suresh; Vaidyanathan, Balu; Krishna, Kumar; Arun, Nair; Supriya, Sudhalkar; Xavier, Joseph; Bhat, Shilpa; Joshi, Suresh; Sharma, Maneesh; Suresh, P V; Shah, Sejal; Mehta, Anamika; Manohari, M; Rajappa, Sujay; Birk, Einat; Berant, Michael; Dagan, Tamir; Folgeman, Rami; Bruckheimer, Elchanan; Razon, Yaron; Amir, Gabriel; Tirosh, Na'ama; Beer, Gil Bayersdorf; Zuker, Nili; Vidne, Bernardo A; Frenkel, Georgy; Rotstein, Amichay; Stein, Riki; De Zorzi, Andrea; Rinelli, Gabriele; Brancaccio, Gianluca; Padrini, Susanna; Carminati, Mario; Micheletti, Angelo; Piazza, Luciane; Fesslova, Wlasta; Rimini, Alessandro; Pongiglione, Giacomo; Pelegrini, Monica; Frau, Federica; Milanesi, Ornella; Maschietto, Nicola; Reffo, Elena; Calabrò, Raffaele; Russo, Maria Giovanna; Caianello, Giuseppe; Morelli, Carmela; Ricci, Concetta; Palladino, Maria Teresa; Carrozza, Marianna; Esposito, Raffaella; Picchio, Fernando Maria; Ragni, Luca; Napoleone, Carlo Pace; Cameli, Daniela; Lee, Jeong Ryul; Kwak, Jae Gun; Park, Chun Soo; Lee, Young Ok; Kandavello, Geetha; Radzi, Nomee Ashikin M; Said, Rozaina Haji M; Maldonado, Roberto; Gutierrez, Maricruz; Cruz, Domitila Vasquez; Roberto, Enriquez; Hernández, Alfonso Buendía; Zabal, Carlos; Cervantes, Jorge Luis; Patiño, Emilia J; García, Jose Antonio; Calderon, Juan; Enríquez, Antonio Juanico; Miranda, Irma; Ramirez, Samuel; Quibrera-Matienzo, Jose A; Perez, Giordano; Palacios-Macedo, Alexis; Monroy, Esteban; Castañuelas, Violeta; Perez, Fabiola; Tamariz, Orlando; Alarcón, Alfredo Vizcaíno; Segura, Begoña; Bolio, Alejandro; Garcia, Rosa Maria; Lozano, Aurora; Balderrabano, Norma; Rodríguez-Hernández, Lydia; Lazo, Charles Cesar; Gonzalez, Julieta; Patiño, Felipe de Jesus; Dominguez, Carlos Alberto; Helbing, Willem A; Seem, Egil; Holmstrom, Henrik; Birkeland, Sigurd; Lindberg, Harald; Kawalec, Wanda; Brodzikowska-Pytel, Anna; Zuk, Malgorzata; Mirecka-Rola, Alicja; Werner, Bo?ena; Florianczyk, Tomasz; Kucinska, Beata; Sysa, Andrzej; Ostrowska, Katarzyna; Jarosik, Piotr; Mazurek-Kula, Anna; Bialkowski, Jacek; Baranowska, Anna; Zeifert, Bozena; Chodor, Beata; Fragata, José Inacio; Nogueira, Graça; Trigo, Conceição; Abecasis, Luis Miguel; Anjos, Rui; Ferreira, Rui; Nogueira, Graça; Areias, José Carlos; Baptista, Maria João; Gorbatykh, Yuriy; Sinelnikov, Yuriy; Leykekhmann, Anastasiya; Latypov, Alexander; Ivanov, Sergey; Krivoshchekov, Evgeny; Volkova, Tamara; Kondratieva, Tamara; Yanulevich, Olga; Shmakova, Natalia; Kulagina, Irina; Kim, Alexey; Ryabtsev, Dmitry; Rogova, Tatyana; Lubomudrov, Vadim; Tsytko, Andrey; Duplyakov, Dmitry; Goryachev, Vladimir; Shorohov, Sergei; Kozeva, Irina; Wong, Keng-Yean; Hong, Tan Teng; Sriram, Shankar; Lawrenson, John; De Decker, Rik; Brown, Stephen; Bruwer, Anari D; Harrisberg, Jeffrey; Karunagaran, Govendrageloo; Cilliers, Antoinette; Adams, Paul E; Van Der Donck, Katharina-Marie; Hoosen, Ebrahim; Nzimela, Andiswa; López, Constancio Medrano; Zunzunegui, José Luis; Maroto, Enrique; Navarro, Nelia; Mora, Andrea; Riaño, Bibiana; Moreno, Laura; Vázquez, María del Carmen; Burgueros, Margarita; Guereta, Luis Garcia; Casares, Jaime; Merino, Carlos; Gómez, Elena; Tejero, Ma Ángeles; Cano, Ana; Carrasco, José Ignacio; Sanchez, Antonio; Núñez, Fernando Rueda; Zavanella, Claudio; Marcos, Sonia; Sunnegardh, Jan; Berggren, Håkan; Nygren, Anders; Lundell, Bo; Prakul, Chanthong; Kritvikrom, Durongpisitkul; Kritvikrom, Durongpisitkul; Kanoknaphat, Chaiyarak; Daubeney, Piers; Slavik, Zdenek; Rowlinson, Giselle; Bu'lock, Frances; Mathur, Sujeev; Mulla, Hussain; Kudumula, Vikram; Raina, Sanjay; Pateman, Alan; Danton, Marck; Richens, Trevor; Knight, Brodie; Weerasena, Nihal A; Blackburn, Mike; Parry, Andrew J; Martin, Robin; Wilson, Dirk; Morgan, Gareth; Forsey, Jonathan; Casey, Francis; Murray, Jane; Shah, Shilpa; Morrison, Louise; Boshkov, Lynn K; Martchenke, Julie; Reller, Mark; Hoffman, Timothy M; Schwartz, Randall; Feltes, Timothy; Justino, Henri; Ocampo, Elene; Jefferies, John Lynn; Jones, Karen; Ing, Frank; Nugent, Allen; Petit, Christopher; Fraser, Charles; McVey, Sarah; Dinu, Bogan; Kay, Joseph D; Ivy, D Dunbar; Da Cruz, Eduardo; O'Brien, James E; Lofland, Gary K; Swihart, Jennifer; Tarrants, Marcy; Patel, Hitendra; Newkumet, Kathleen; Culbertson, Casey; Reinhartz, Olaf; Pizarro, Christian; Derby, Christopher; Rome, Jonathan J; Ravishankar, Chitra; Anderson, Terry; Gleason, Marie; Natrajan, Shobha; Rosenthal, David N; Shin, Andrew; Roth, Stephen; Poole, Robert; Tran, Ming; Sullivan, Janice E; Mascio, Christopher E; Austin, Erle; Condurache, Carmen; Myers, Amanda; Recto, Michael; Suttner, Denise; Frazer, Jeff; Lane, Brian; Knight, Gail; Teitel, David F; Moore, Phillip; Tacy, Theresa; Aluquin, Vincent; Stokes, Jennifer; Sturgis, Sarah; Johnson, Gerard; Watts, Heidi; Myers, John; McMonagle, Amylee; Clark, Joseph; Jones, Julie; Manbachi, Rosemary; Porter, Penny; Shaner, Marie; Van Bergen, Andrew; Husayni, Tarek; Nguyen, Nguyenvu; Sajan, Imran; Thompson, James A; Callahan, Patrick; Charpie, John R; Armstrong, Aimee K; Gajarski, Robert J; Aiyagari, Rangit; Covitz, Wesley; Cnota, James F; Crawford, Kari; Dobrolet, Nancy C; Nieves, Jo Ann; Forbus, Geoffrey A; Atz, Andrew; Huhta, James; Sieasman, John W; Emmanuel, Patricia J; Quintessenza, James; Chai, Paul; Jacobs, Jeffrey; Lizarralde, Jose; Boston, Umar; Myers, Jeff L; Lutterman, Joel; Gilbert, Christian; Cabrera, Antonio; Mathis, Craig; Tugertimur, Aykut; Nykanen, David G; Camitta, Michael G W; Anderson, Page; Rhodes, John; Li, Jennifer; Barker, Piers; Miller, Stephen; Milazzo, Angelo; Scholz, Thomas; Pardini, Benet; Pierick, Trudy; Mahle, William T; Simsic, Janet; Kanter, Kirk; Kirshbom, Paul; Kogon, Brian; Bajaj, Tanya; Huckaby, Jeryl; Pugsley, Lisa; Spainhour, Christine; Dieleman, Leticia; Jensen, Deanna; Giannopoulos, Helen; Wilkey, Sheila; Lamphier, Carey; Rhodes, James; Dukes, Shannon Austin; Bond, Joel; Siu, Benjamin; Schutte, Deborah; Turner, Daniel; Walters, Henry; Delius, Ralph; McGivern, Janet; Sullivan, Nancy; Storie, Kristin; Kennedy, Kristin; Forbes, Thomas; Srinath, Gowdagere; Kumar, Anil; Parikh, Sanjay; Berger, John T; Cross, Russell R; Heath, Deneen M; Odegard, Kirsten; Jenkins, Kathy; DiNardo, James; Connor, Jean; Maltz, Lily; Taylor, Mary; Christian, Karla G; Liske, Michael R; Shalaby, Theresa M; Arnold, Judi M; Leizorovicz, Alain; Danielson, Linda; Michelson, Alan; Sanders, Stephen S; Wessel, David L; Berger, Felix; Brown, Stephen; Feltes, Timothy; Fraisse, Alain; Li, Jennifer S; Medrano, Constancio; Mertens, Luc; Mulinari, Leonardo Andrade; Palacios-Macedo, Alexis; Newburger, Jane W; Rao, Suresh; Newburger, Jane W; Berger, Felix; Brown, Stephen; Dunbar-Masterson, Carolyn; Feltes, Timothy; Fraisse, Alain; Geva, Judith; Medrano, Constancio; Mertens, Luc; Mulinari, Leonardo Andrade; Palacios-Macedo, Alexis; Rao, Suresh     «

Wessel, David L; Berger, Felix; Li, Jennifer S; Dähnert, Ingo; Rakhit, Amit; Fontecave, Sylvie; Newburger, Jane W; CLARINET Investigators; Trentadue, Julio; Gutierrez, Diego; Antoni, Diego; Toledo, Ruben; Parodi, Willy Conejeros; Guerrero, Rafael; Klinger, Daniel; Magliola, Ricardo; Mazzucchelli, Maria Teresa; Moreno, Mariano; Bellani, Patricia; Couceiro, Claudia; Marantz, Pablo; Rosselot, Silvina; Benmaor, Lisandro; Elorriaga, Maria Sol; Peña, Gabriela; Somoza, Felipe; Romero, Sandra; Barrea, C...     »

Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related to the shunt.In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pulmonary-artery shunt to receive clopidogrel at a dose of 0.2 mg per kilogram of body weight per day (467 infants) or placebo (439 infants), in addition to conventional therapy (including aspirin in 87.9% of infants). The primary efficacy end point was a composite of death or heart transplantation, shunt thrombosis, or performance of a cardiac procedure due to an event considered to be thrombotic in nature before 120 days of age.The rate of the composite primary end point did not differ significantly between the clopidogrel group (19.1%) and the placebo group (20.5%) (absolute risk difference, 1.4 percentage points; relative risk reduction with clopidogrel, 11.1%; 95% confidence interval, -19.2 to 33.6; P=0.43), nor did the rates of the three components of the composite primary end point. There was no significant benefit of clopidogrel treatment in any subgroup, including subgroups defined by shunt type. Clopidogrel recipients and placebo recipients had similar rates of overall bleeding (18.8% and 20.2%, respectively) and severe bleeding (4.1% and 3.4%, respectively).Clopidogrel therapy in infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary-artery shunt, most of whom received concomitant aspirin therapy, did not reduce either mortality from any cause or shunt-related morbidity. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00396877.).     «

Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related to the shunt.In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pulmonary-artery shunt to receive cl...     »