Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study.
BACKGROUND
Clinical trials are needed to assess the clinical benefit of antithrombotic prophylaxis in patients with cancer who are receiving chemotherapy, since these patients are at an increased risk of developing a thromboembolism. We did a trial to assess the clinical benefit of the low-molecular-weight heparin nadroparin for the prophylaxis of thromboembolic events in ambulatory patients receiving chemotherapy for metastatic or locally advanced solid cancer.


METHODS
Between October, 2003, and May, 2007, ambulatory patients with lung, gastrointestinal, pancreatic, breast, ovarian, or head and neck cancer were randomly assigned in a double-blind manner to receive subcutaneous injections of nadroparin (3800 IU anti-Xa once a day, n=779) or placebo (n=387), in a 2:1 ratio. Study treatment was given for the duration of chemotherapy up to a maximum of 4 months. The primary study outcome was the composite of symptomatic venous or arterial thromboembolic events, as assessed by an independent adjudication committee. All randomised patients who received at least one dose of study treatment were included in the efficacy and safety analyses (modified intention-to-treat population). The study is registered with ClinicalTrials.gov, NCT 00951574.


RESULTS
1150 patients were included in the primary efficacy and safety analyses: 769 patients in the nadroparin group and 381 patients in the placebo group. 15 (2.0%) of 769 patients treated with nadroparin and 15 (3.9%) of 381 patients treated with placebo had a thromboembolic event (single-sided p=0.02). Five (0.7%) of 769 patients in the nadroparin group and no patients in the placebo group had a major bleeding event (two-sided p=0.18). The incidences of minor bleeding were 7.4% (57 of 769) with nadroparin and 7.9% (30 of 381) with placebo. There were 121 (15.7%) serious adverse events in the nadroparin goup and 67 (17.6%) serious adverse events in the placebo group.


CONCLUSIONS
Nadroparin reduces the incidence of thromboembolic events in ambulatory patients with metastatic or locally advanced cancer who are receiving chemotherapy. Future studies should focus on patients who are at a high risk for thromboembolic events.


BACKGROUND
Italfarmaco SpA, Milan, Italy.
Agnelli
Giancarlo
G
Internal and Vascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy. agnellig@unipg.it
Gussoni
Gualberto
G
Bianchini
Carlo
C
Verso
Melina
M
Mandalà
Mario
M
Cavanna
Luigi
L
Barni
Sandro
S
Labianca
Roberto
R
Buzzi
Franco
F
Scambia
Giovanni
G
Passalacqua
Rodolfo
R
Ricci
Sergio
S
Gasparini
Giampietro
G
Lorusso
Vito
V
Bonizzoni
Erminio
E
Tonato
Maurizio
M
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D017762:Nadroparin / Q000008:administration & dosage*; D009369:Neoplasms / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D013923:Thromboembolism / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D000970:Antineoplastic Agents; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D017762:Nadroparin