From ASH:
>>[558] Oral SNAC-Heparin vs. Enoxaparin for Preventing Venous Thromboembolism Following Total Hip
Replacement.
Russell D. Hull, Ajay K. Kakkar, Victor J. Marder, Graham F. Pineo, Michael M. Goldberg, Gary E. Raskob, for the
PROTECT Trial. Thrombosis Research Unit, University of Calgary, Calgary, AB, Canada; Thrombosis Research
Institute, London, United Kingdom; Vascular Medicine Program, Orthopedic Hospital, Los Angeles, CA, USA;
Emisphere Technologies, Inc., Tarrytown, NY, USA; Health Sciences Center, University of Oklahoma, Oklahoma
City, OK, USA
Background: The addition of N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) to unfractionated heparin (UFH)
markedly enhances its oral absorption. We report the findings of a phase III clinical trial comparing two liquid-doses of
SNAC heparin given orally with the low-molecular-weight heparin enoxaparin (LMWH) by subcutaneous injection for
the prevention of venous thromboembolism in patients undergoing total hip replacement. Methods: We performed a
double-blind (double-dummy: placebo oral or injection) randomized clinical trial in patients undergoing elective hip
surgery comparing low dose SNAC/heparin (ldSNAC), high dose SNAC/heparin (hdSNAC) and subcutaneous
LMWH/ oral placebo. SNAC/heparin was administered for 30 days and LMWH, 30 mg q12h, was administered for
10 days and oral placebo out to 30 days. Ascending contrast venography was performed routinely in all patients on day
27-30. For each treatment group 743 patients were required to obtain 90% power for analysis of the deep-vein
thrombosis (DVT) rates (type I error of 0.025) assuming an interpretable venogram rate of 65%. Results: Interpretable
venogram population: A total of 752, 767, and 745 patients were randomized to the ldSNAC, hdSNAC and
LMWH/placebo groups respectively; interpretable venography was obtained in 64% of patients. Baseline
characteristics on entry were comparable among the groups. Results showed that 155 of 488 (31.8%), 137 of 461
(29.7%) and 117 of 449 (26.1%) patients in the ldSNAC, hdSNAC and LMWH/ oral placebo groups respectively
had documented DVT or pulmonary embolism (PE) (the absolute differences and 95% CI for ldSNAC and hdSNAC
compared with LMWH were: 5.7% [0.1% to 11.7% CI] and 3.7% [-1.9% to 9.7% CI]) . Proximal DVT or PE
occurred in 90 of 485 (18.6%), 64 of 465 (13.8%) and 57 of 450 (12.7%) evaluable patients for ldSNAC, hdSNAC
and LMWH/placebo respectively (p=0.013 comparing ldSNAC to LMWH/placebo and p=0.045 comparing
hdSNAC to ldSNAC). Major bleeding was rare and comparable among groups. Per-protocol analysis: Unexpectedly,
poor compliance to the oral regimen became an issue: poor compliance occurred in 22.1% (ldSNAC), 31.4%
(hdSNAC) and 12.7% (LMWH/ oral placebo). A per-protocol analysis taking into account failure of compliance and
use of routine thromboprophylaxis in the noncompliers showed findings consistent with those for the interpretable
venogram population. Discussion: Our findings provide proof of concept that clinically relevant antithrombotic protection
can be achieved by orally administered UFH. Compared with ldSNAC, hdSNAC showed clinical and statistical
superiority for proximal DVT or PE, a dose-response effect. A solid formulation with improved patient tolerability is
under development.
Keywords: Oral heparin\ SNAC\ Thromboprophylaxis<<
So clinically relevant, but not quite as good as LMWH, and compliance is a major issue. Hmmm. What do you think, MZ? I was expecting a bit better.
Cheers, Tuck |
