Liver CancerPhase 4PREPOSTEROUSNCT04731558
Pre- Vs Postoperative Thromboprophylaxis for Liver Resection
A Phase 4 study testing enoxaparin or tinzaparin or dalteparin in people with Liver Cancer and Surgery, run by Helsinki University Central Hospital at 7 sites in 2 countries.
Trial summary
Thromboprophylaxis for liver surgery can be commenced either preoperatively or postoperatively. Despite a clear trade-off between thrombosis and bleeding in liver surgery patients, there is no international consensus when thrombosis prophylaxis should be commenced in patients undergoing liver surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cancer, Surgery, Thrombosis, Deep Vein
- What is being tested?
- enoxaparin or tinzaparin or dalteparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,012 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 10 Feb 2021to Mar 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients undergoing liver resection
Who cannot join
- Patient on anticoagulative medication (heparin, low-molecular weight heparin, warfarin, direct oral anticoagulants) during last month pre-surgery
- Emergency operation (e.g. for trauma or infection)
- Age < 18 years
- Allergy or other contraindication to planned low-molecular weight heparin
- Inability to give written informed consent
- Liver resection not performed (removed from analyses after randomization)
Trial locations and contacts
7 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
7 sites in 2 countries
Finland5 sites, 5 recruiting
- Recruiting
Helsinki University Hospital
Helsinki
Aki Uutela, MD, +358-9-4711, aki.uutela@hus.fi
- Recruiting
Kuopio University Hospital
Kuopio
Pekka Lammi, MD, pekka.lammi@kys.fi
- Not yet recruiting
Oulu University Hospital
Oulu
Heikki Karjula, MD, PhD, heikki.karjula@ppshp.fi
- Recruiting
Tampere University Hospital
Tampere
Yrjö Vaalavuo, MD, yrjo.vaalavuo@pshp.fi
- Not yet recruiting
Turku University Hospital
Turku
Maija Lavonius, MD, maija.lavonius@tyks.fi
Norway2 sites, 2 recruiting
- Recruiting
Oslo University Hospital
Oslo
Sheraz Yaqib, MD, shya@ous-hf.no
- Recruiting
University Hospital of North Norway
Tromsø
Kim E Mortensen, MD, PhD, +47 77 62 60 00, Kim.Erlend.Mortensen@unn.no
About this study
Official title: Pre- Vs Postoperative Thromboprophylaxis for Liver Resection - a Prospective, Multicenter, Randomized Controlled Trial
Thromboprophylaxis for liver surgery can be commenced either preoperatively or postoperatively. Despite a clear trade-off between thrombosis and bleeding in liver surgery patients, there is no international consensus when thrombosis prophylaxis should be commenced in patients undergoing liver surgery. As far as we know, there are no prospective randomized trials in this field, and current guidelines are unfortunately based on very low quality evidence, that is, a few retrospective studies and expert opinion. Both American and European thromboprophylaxis guidelines for abdominal cancer surgery support the preoperative initiation of thromboprophylaxis, but these guidelines do not specifically address the increased bleeding risk associated with liver surgery. On the contrary, Dutch guidelines recommend postoperative thromboprophylaxis only, because of lack of evidence for preoperative thromboprophylaxis. Traditionally, many liver surgery units have been reluctant in using preoperative thromboprophylaxis due to the potentially increased risk of bleeding complications. Enhanced Recovery After Surgery (ERAS) Society Guidelines recommend preoperative thromboprophylaxis in liver surgery, but the guidelines provide no supporting evidence for this recommendation. Overall, the amount of evidence is scarce and somewhat contradictory in this clinically relevant field of thromboprophylaxis in liver surgery. The aim of this study is to compare pre- and postoperatively initiated thromboprophylaxis regimens in liver surgery in a randomized controlled trial.
- Conditions
- Liver Cancer, Surgery, Thrombosis, Deep Vein, Embolism, Pulmonary, Bleeding
- Being tested
- enoxaparin or tinzaparin or dalteparin, No intervention
- Medical subject headings
- Liver Neoplasms, Venous Thrombosis, Pulmonary Embolism, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enoxaparin or tinzaparin or dalteparinDrug
Thromboprophylaxis initiated approximately 14 hours prior to the planned liver resection skin incision. Thromboprophylaxis can be initiated using enoxaparin (20 - 40 mg), tinzaparin (2500 - 4500 IU), or dalteparin (2500 - 5000 IU), with the dose based on patient's renal function
No interventionDrug
No preoperative thromboprophylaxis.
| Study group | Role | What they receive |
|---|---|---|
| Preoperative thromboprophylaxis | Experimental | Preoperatively initiated tromboprophylaxis Receives: Drug: enoxaparin or tinzaparin or dalteparin |
| Postoperative thromboprophylaxis | Other | Postoperatively initiated thromboprophylaxis Receives: Drug: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Venous thromboembolisms
Number of patients with venous thromboembolism defined as either 1) symptomatic deep venous thromboembolism (includes all deep veins e.g. all extremities, portal vein, and superior mesenteric) diagnosed using ultrasound or computed tomography or magnetic resonance imaging, or in re-laparatomy/surgery, 2) pulmonary embolism diagnosed using computed tomography, magnetic resonance imaging, or lung perfusion imaging, or 3) death due to venous thromboembolism
Measured: within 30 days from liver resection
Secondary outcomes (4)
Posthepatectomy haemorrhage
Number of patients with posthepatectomy haemorrhage, any grade in ISGLS classification
Measured: within 30 days from liver resection
Postoperative complications
Comprehensive Complication Index - score
Measured: within 30 days from liver resection
Length of postoperative hospital stay
Length of postoperative hospital stay, days
Measured: within 30 days from liver resection
Blood transfusion
Total amount of transfused red blood cells, units
Measured: during and within 30 days from liver resection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2021
- Study start10 Feb 2021
- Primary completionFeb 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,012 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Academy of Finland, The Finnish Medical Association
- Responsible party
- Principal investigator, Ville Sallinen, Helsinki University Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04731558
- Sponsor's protocol ID
- HYKS-PREPOSTEROUS
- Acronym
- PREPOSTEROUS
- Status last verified
- Feb 2025
- First submitted
- 26 Jan 2021
- Last updated
- 14 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre- Vs Postoperative Thromboprophylaxis for Liver Resection - a Prospective, Multicenter, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04731558
- Acronym / sponsor ID
- PREPOSTEROUS / HYKS-PREPOSTEROUS
- Conditions
- Liver Cancer, Surgery, Thrombosis, Deep Vein, Embolism, Pulmonary, Bleeding
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,012 participants (estimated)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Collaborators
- Academy of Finland, The Finnish Medical Association
- Study start
- 10 Feb 2021 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 1 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Thromboprophylaxis for liver surgery can be commenced either preoperatively or postoperatively. Despite a clear trade-off between thrombosis and bleeding in liver surgery patients, there is no international consensus when thrombosis prophylaxis should be commenced in patients undergoing liver surgery. As far as we know, there are no prospective randomized trials in this field, and current guidelines are unfortunately based on very low quality evidence, that is, a few retrospective studies and expert opinion. Both American and European thromboprophylaxis guidelines for abdominal cancer surgery support the preoperative initiation of thromboprophylaxis, but these guidelines do not specifically address the increased bleeding risk associated with liver surgery. On the contrary, Dutch guidelines recommend postoperative thromboprophylaxis only, because of lack of evidence for preoperative thromboprophylaxis. Traditionally, many liver surgery units have been reluctant in using preoperative thromboprophylaxis due to the potentially increased risk of bleeding complications. Enhanced Recovery After Surgery (ERAS) Society Guidelines recommend preoperative thromboprophylaxis in liver surgery, but the guidelines provide no supporting evidence for this recommendation. Overall, the amount of evidence is scarce and somewhat contradictory in this clinically relevant field of thromboprophylaxis in liver surgery. The aim of this study is to compare pre- and postoperatively initiated thromboprophylaxis regimens in liver surgery in a randomized controlled trial.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Preoperative thromboprophylaxis | Experimental | Drug: enoxaparin or tinzaparin or dalteparinPreoperatively initiated tromboprophylaxis |
| Postoperative thromboprophylaxis | Other | Drug: No interventionPostoperatively initiated thromboprophylaxis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients undergoing liver resection
Key exclusion criteria (6 listed)
- Patient on anticoagulative medication (heparin, low-molecular weight heparin, warfarin, direct oral anticoagulants) during last month pre-surgery
- Emergency operation (e.g. for trauma or infection)
- Age < 18 years
- Allergy or other contraindication to planned low-molecular weight heparin
- Inability to give written informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| enoxaparin or tinzaparin or dalteparinThromboprophylaxis initiated approximately 14 hours prior to the planned liver resection skin incision. Thromboprophylaxis can be initiated using enoxaparin (20 - 40 mg), tinzaparin (2500 - 4500 IU), or dalteparin (2500 - 5000 IU), with the dose based on patient's renal function | Drug | Preoperative thromboprophylaxis |
| No interventionNo preoperative thromboprophylaxis. | Drug | Postoperative thromboprophylaxis |
Primary outcome
Venous thromboembolisms
Time frame: within 30 days from liver resection
Number of patients with venous thromboembolism defined as either 1) symptomatic deep venous thromboembolism (includes all deep veins e.g. all extremities, portal vein, and superior mesenteric) diagnosed using ultrasound or computed tomography or magnetic resonance imaging, or in re-laparatomy/surgery, 2) pulmonary embolism diagnosed using computed tomography, magnetic resonance imaging, or lung perfusion imaging, or 3) death due to venous thromboembolism
4 secondary outcomes
Posthepatectomy haemorrhage
Time frame: within 30 days from liver resection
Postoperative complications
Time frame: within 30 days from liver resection
Length of postoperative hospital stay
Time frame: within 30 days from liver resection
Blood transfusion
Time frame: during and within 30 days from liver resection
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing enoxaparin or tinzaparin or dalteparin in people with Liver Cancer and Surgery, run by Helsinki University Central Hospital at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Finland, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ville Sallinen, MD, PhD (+358-9-4711, ville.sallinen@helsinki.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Venous thromboembolisms (time frame: within 30 days from liver resection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2025.