Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial

CATCH Investigators

Research output: Contribution to journalArticle

287 Citations (Scopus)

Abstract

Importance: Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial. Objective: To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. Design, Settings, and Participants: A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30days after the last study medication dose for collection of safety data. Interventions: Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed bywarfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months. Main Outcomes and Measures: Primary efficacy outcomewas a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality. Results: Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2% for tinzaparin vs 10.5% for warfarin; hazard ratio [HR], 0.65 [95% CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95% CI, 0.40-1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95% CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95% CI, 0.40-0.84]; P = .004). Conclusions and Relevance: Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE.

Original languageEnglish
Pages (from-to)677-686
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume314
Issue number7
DOIs
StatePublished - 18 Aug 2015

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Venous Thromboembolism
Warfarin
Randomized Controlled Trials
Neoplasms
Hemorrhage
Therapeutics
Safety
tinzaparin
Pulmonary Embolism
Venous Thrombosis
Mortality
Outcome Assessment (Health Care)
Central America
International Normalized Ratio
South America
Low Molecular Weight Heparin
North America
Life Expectancy

Cite this

@article{59f5d0a9a2594a4da10f47d4b1fe746a,
title = "Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial",
abstract = "Importance: Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial. Objective: To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. Design, Settings, and Participants: A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30days after the last study medication dose for collection of safety data. Interventions: Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed bywarfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months. Main Outcomes and Measures: Primary efficacy outcomewas a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality. Results: Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2{\%} for tinzaparin vs 10.5{\%} for warfarin; hazard ratio [HR], 0.65 [95{\%} CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95{\%} CI, 0.40-1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95{\%} CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95{\%} CI, 0.40-0.84]; P = .004). Conclusions and Relevance: Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE.",
author = "{CATCH Investigators} and Lee, {Agnes Y.Y.} and Kamphuisen, {Pieter W.} and Guy Meyer and Rupert Bauersachs and Janas, {Mette S.} and Jarner, {Mikala F.} and Khorana, {Alok A.} and Rafael, {Bella Santiago} and Cerana Susana and Jos{\'e}, {Zarb{\'a} Juan} and Johannes Andel and Henrique, {Barrios Carlos} and Andr{\'e}, {Borba Reiriz} and Cesario Fabiane and S{\'e}rgio, {De Azevedo} and Fabiano, {Ferreira Filho Antonio} and Andr{\'e}, {Franke F{\'a}bio} and Padilha Sergio and Renata, {Paiva Queiroz} and Pimenta Alex and Rerin J{\'u}lio and Rigo Rodrigo and Brigitte, {Rocha Van Eyll Sylvie} and Giuliano, {Santos Borges} and Vacaro Giovana and Anastasov Vasil and Dragneva Tanya and Georgiev Georgi and Champion Philip and Kuruvilla Philip and Gonzalez Carolina and Ditl Pavel and F{\"o}rster Jiř{\'i} and Lubomir Buncek and Vydra Jan and Rasha, {Abo El Hassan} and Sabri Sherif and Allahloubi Nasr and Elzawawy Ahmed and Saad, {Ezzat Safwat} and Mohamed, {Sabry El Kady} and Bauersachs Rupert and Bacchus Liza and Jan, {Beyer Westendorf} and Kamphausen Ulrich and Niederwieser Dietger and Ostermann Helmut and Sosada Markus and Anagnostopoulos Nikolas and Fountzilas George",
year = "2015",
month = "8",
day = "18",
doi = "10.1001/jama.2015.9243",
language = "English",
volume = "314",
pages = "677--686",
journal = "JAMA - Journal of the American Medical Association",
issn = "0098-7484",
publisher = "American Medical Association",
number = "7",

}

Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer : A randomized clinical trial. / CATCH Investigators.

In: JAMA - Journal of the American Medical Association, Vol. 314, No. 7, 18.08.2015, p. 677-686.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer

T2 - A randomized clinical trial

AU - CATCH Investigators

AU - Lee, Agnes Y.Y.

AU - Kamphuisen, Pieter W.

AU - Meyer, Guy

AU - Bauersachs, Rupert

AU - Janas, Mette S.

AU - Jarner, Mikala F.

AU - Khorana, Alok A.

AU - Rafael, Bella Santiago

AU - Susana, Cerana

AU - José, Zarbá Juan

AU - Andel, Johannes

AU - Henrique, Barrios Carlos

AU - André, Borba Reiriz

AU - Fabiane, Cesario

AU - Sérgio, De Azevedo

AU - Fabiano, Ferreira Filho Antonio

AU - André, Franke Fábio

AU - Sergio, Padilha

AU - Renata, Paiva Queiroz

AU - Alex, Pimenta

AU - Júlio, Rerin

AU - Rodrigo, Rigo

AU - Brigitte, Rocha Van Eyll Sylvie

AU - Giuliano, Santos Borges

AU - Giovana, Vacaro

AU - Vasil, Anastasov

AU - Tanya, Dragneva

AU - Georgi, Georgiev

AU - Philip, Champion

AU - Philip, Kuruvilla

AU - Carolina, Gonzalez

AU - Pavel, Ditl

AU - Jiří, Förster

AU - Buncek, Lubomir

AU - Jan, Vydra

AU - Rasha, Abo El Hassan

AU - Sherif, Sabri

AU - Nasr, Allahloubi

AU - Ahmed, Elzawawy

AU - Saad, Ezzat Safwat

AU - Mohamed, Sabry El Kady

AU - Rupert, Bauersachs

AU - Liza, Bacchus

AU - Jan, Beyer Westendorf

AU - Ulrich, Kamphausen

AU - Dietger, Niederwieser

AU - Helmut, Ostermann

AU - Markus, Sosada

AU - Nikolas, Anagnostopoulos

AU - George, Fountzilas

PY - 2015/8/18

Y1 - 2015/8/18

N2 - Importance: Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial. Objective: To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. Design, Settings, and Participants: A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30days after the last study medication dose for collection of safety data. Interventions: Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed bywarfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months. Main Outcomes and Measures: Primary efficacy outcomewas a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality. Results: Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2% for tinzaparin vs 10.5% for warfarin; hazard ratio [HR], 0.65 [95% CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95% CI, 0.40-1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95% CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95% CI, 0.40-0.84]; P = .004). Conclusions and Relevance: Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE.

AB - Importance: Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial. Objective: To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. Design, Settings, and Participants: A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30days after the last study medication dose for collection of safety data. Interventions: Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed bywarfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months. Main Outcomes and Measures: Primary efficacy outcomewas a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality. Results: Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2% for tinzaparin vs 10.5% for warfarin; hazard ratio [HR], 0.65 [95% CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95% CI, 0.40-1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95% CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95% CI, 0.40-0.84]; P = .004). Conclusions and Relevance: Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE.

UR - http://www.scopus.com/inward/record.url?scp=84940649946&partnerID=8YFLogxK

U2 - 10.1001/jama.2015.9243

DO - 10.1001/jama.2015.9243

M3 - Article

C2 - 26284719

AN - SCOPUS:84940649946

VL - 314

SP - 677

EP - 686

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0098-7484

IS - 7

ER -