Patients in intensive care units (ICUs) are at high risk of developing blood clots, particularly venous thrombosis. Preventive anticoagulants are routinely administered as daily subcutaneous injections, yet thrombosis still occurs in 5-37% of patients – a phenomenon known as thromboprophylaxis failure. Risk factors include conditions such as cancer and obesity. In these cases, some experts recommend higher-dose preventive anticoagulation (doubling the standard dose), while others caution that this may increase bleeding risk, resulting in variable usual practices.
A total of 606 ICU patients with high risk of thromboprophylaxis failure and low bleeding risk will be randomly (random draw) assigned to receive either the standard or a higher dose of preventive anticoagulation for up to 28 days. The primary endpoint will be the net clinical outcome at day 28, combining thrombosis, severe bleeding, and all-cause mortality. Because the study is blinded, neither the patients nor the caregivers will know which dose is being administered.
| Title | Standard-dose versus high-dose prophylactic anticoagulation in critically ill medical patients at risk for thromboprophylaxis failure: a multicentre, parallel-group, double-blind, phase III, randomized controlled trial |
| Participants (P) | Adult medical patients requiring ICU admission for at least three days with a high risk of thromboprophylaxis failure and a low baseline risk for bleeding |
| Intervention (I) | In addition to the low-dose prophylaxis, the participants will receive a blinded study drug, either enoxaparin 4,000 IU (0.4 ml) or placebo (sodium chloride 0.9%, 0.4 ml). This study drug will be administered once daily by subcutaneous injection, 12 hours after the open-label enoxaparin SC, for 28 days or until ICU discharge, whichever comes first. |
| Control (C) | All participants will receive a daily open-label dose of enoxaparin 4,000 IU (0.4 ml) in a pre-filled syringe by subcutaneous injection for 28 days or until ICU discharge (whichever comes first) as part of usual care, regardless of their assignment to the intervention or placebo arm. |
| Outcome (O) | Compare the efficacy and safety of HD-PA (4,000 IU twice daily) and SD-PA (SD-PA, 4,000 IU once daily) at Day 28 in terms of the net clinical outcome, which is a composite of venous thrombosis, major bleeding, or mortality. Primary endpoint: The primary combined efficacy and safety outcome at Day 28 is the net clinical outcome, which is a composite of clinically relevant venous thrombosis (symptomatic isolated distal leg deep venous thrombosis (DVT), proximal leg DVT, pulmonary embolism (PE) [except subsegmental], extensive central venous catheter (CVC)-related DVT), major bleeding (as per the International Society on Thrombosis and Hemostasis (ISTH) definition), all-cause death. |
| Trial Design | HIPRO is a multicenter, prospective, randomized, double-blind, phase 3 trial designed to compare high-dose prophylactic anticoagulation (HD-PA) to standard dose of prophylactic anticoagulation (SD-PA) in a 1:1 ratio in adult patients admitted to the ICU with a high risk for thromboprophylaxis failure and a low baseline risk for bleeding. The primary combined efficacy and safety outcome is the net clinical outcome, assessed at day 28, defined as a composite of clinically relevant venous thrombosis, major bleeding, or all-cause death. |
| Sample Size | 606 |
| Trial duration | 42 months |
| Budget | 2.63 Mio € |
| Sponsor | HUB (Erasme) |
| Chief Investigator | Prof. Dr. Vincent Labbé |
| External partners | CRO CHU Mondor – France (TBC) |
| Number of participating sites | 12 |
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