Extended Thromboprophylaxis for Postoperative Clot Prevention in Liver Cancer Surgery

(PRIORITY Trial)

Overseen By Crystal Engelage, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Western University, Canada

Must be taking: Low molecular weight heparins

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Thrombotic events, Coagulation disorder, Thrombophilia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 30-90 days

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants are not on current anticoagulant or antiplatelet therapy, so you would need to stop these medications to participate.

What data supports the effectiveness of the drug Fragmin, Redesca for preventing clots after liver cancer surgery?

Research shows that extended anticoagulation (blood thinning) after liver surgery is safe and effective, with one study reporting no clotting events in 124 patients. This suggests that using blood thinners like Fragmin and Redesca can help prevent clots after liver cancer surgery. ^{1 2 3 4 5}

Is the treatment for preventing blood clots after liver cancer surgery safe?

The treatment, using Fragmin, has been shown to be generally safe in humans for preventing blood clots after surgery, with no severe adverse reactions or drug-related deaths reported in studies. It is effective in reducing the risk of blood clots with a low incidence of bleeding complications. ^{2 3 6 7 8}

How is extended thromboprophylaxis unique for preventing clots after liver cancer surgery?

Extended thromboprophylaxis is unique because it involves prolonged use of anticoagulants (blood thinners) after liver cancer surgery, which has been shown to be safe and effective in preventing blood clots without increasing bleeding risks, unlike standard shorter-duration treatments. ^{1 2 3 4 9}

What is the purpose of this trial?

This clinical trial will investigate the ability of thromboelastrogrpahy (TEG®) to detect hypercoagulability after liver surgery and will examine the effect of extended thromboprophylaxis (medical treatment to prevent the development of blood clots inside blood vessels) in patients undergoing liver surgery for cancer treatment. The liver plays a key role in regulating the process of blood clotting. As a result, blood clots are a major cause of complications and death following liver surgery. This is especially true in cancer patients who are at a higher risk of developing blood clots. Current methods for preventing clotting complications after liver surgery include conventional coagulation blood tests (CCTs) and anticoagulant drugs, such as low molecular weight heparins (LMWHs). Current LMWH treatment is prescribed for one month after surgery, but studies show that the risk of developing blood clots can last up to 3 months. Studies also show that CCTs may not be as effective in detecting clotting issues as more comprehensive testing systems, such as TEG. This study will randomize 50 participants to receive 90 days of thromboprophylaxis (using the LMWH Redesca) or the standard of care 30 days (using the LMWH Fragmin) after liver surgery. The medication will be given by injection, similar to a regular vaccine or an insulin injection. Participants will inject the medication every day, for 30 or 90 days, after surgery. Participants will also have their blood tested for clotting issues via TEG testing before surgery and on post-operative days 1,3,5,30 and 90. After surgery, participants will be monitored by their surgeon for clotting complications and 3 year disease-free survival.

Research Team

Anton Skaro, MD PhD

Principal Investigator

Western Univeristy/LHSC

Eligibility Criteria

This trial is for adults over 18 who need major liver surgery for cancer and require blood clot prevention after. They must be able to do or receive daily injections. It's not for those under 18, on current blood thinners, with a history of clots, bleeding disorders, known clotting conditions, or unable to understand English.

Inclusion Criteria

I need a major surgery to remove part of my liver for cancer.

I need medication to prevent blood clots after surgery.

I can give myself injections or have someone who can do it for me.

Exclusion Criteria

I am under 18 years old.

I am currently on blood thinners.

I have had blood clots in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Testing

Participants undergo TEG testing and pre-admission blood work

1 week

1 visit (in-person)

Treatment

Participants receive thromboprophylaxis with either Redesca for 90 days or Fragmin for 30 days post-surgery

30-90 days

Daily self-injections

Postoperative Monitoring

Participants are monitored for clotting complications and undergo TEG testing on post-operative days 1, 3, 5, 30, and 90

90 days

5 visits (in-person)

Follow-up

Participants are monitored for thrombotic events and disease-free survival

Up to 3 years

Treatment Details

Interventions

• Fragmin
• Redesca

Trial Overview The study tests if extended use of Redesca (90 days) is better than the standard Fragmin treatment (30 days) at preventing blood clots after liver surgery. Participants will self-inject daily and have their blood tested regularly using TEG® to monitor clotting.

Participant Groups

Group I: Redesca Experimental Treatment 1 Intervention

Patients in the extended thromboprophylaxis group will receive Redesca (enoxaparin sodium for injection) (40mg) once a day, starting on the day of surgery, for 90 days postoperatively.

Group II: Fragmin Active Control 1 Intervention

Patients in the standard of care group will receive Fragmin (daletparin) (5,000 I.U) once a day, starting on the day or surgery, for 30 days postoperatively.

Who Is Running the Clinical Trial?

Western University, Canada

Lead Sponsor

Trials

270

Recruited

62,500+

Valeo Pharma Inc

Collaborator

Trials

1

Recruited

50+

Findings from Research

In a study involving 614 patients undergoing colorectal cancer surgery, extended duration thromboprophylaxis with tinzaparin did not significantly improve disease-free survival compared to standard in-hospital thromboprophylaxis, with similar outcomes observed in both groups.

The rates of venous thromboembolism and major bleeding complications were low and comparable between the extended duration and in-hospital groups, indicating that both approaches are safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of extended duration to perioperative thromboprophylaxis with low molecular weight heparin on disease-free survival after surgical resection of colorectal cancer (PERIOP-01): multicentre, open label, randomised controlled trial. Auer, RC., Ott, M., Karanicolas, P., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of extended duration to perioperative thromboprophylaxis with low molecular weight heparin on disease-free survival after surgical resection of colorectal cancer (PERIOP-01): multicentre, open label, randomised controlled trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Extended pharmacologic thromboprophylaxis in oncologic liver surgery is safe and effective. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Post-operative pharmacologic thromboprophylaxis after major hepatectomy: does peripheral venous thromboembolism prevention outweigh bleeding risks? [2021]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pharmacological venous thromboembolism prophylaxis following liver resection: a systematic review and meta-analysis. [2018]

5. Italy pubmed.ncbi.nlm.nih.gov

Prevention of venous thromboembolism after resection of primary liver cancer with low molecular weight heparin and its association with P-selectin, lysosomal granule glycoprotein, platelet activating factor and plasma D-dimer. [2019]

6. Italy pubmed.ncbi.nlm.nih.gov

[Evaluation of the effectiveness and safety of Fragmin (Kabi 2165) versus calcium heparin in the prevention of deep venous thrombosis in general surgery]. [2006]

7. Germany pubmed.ncbi.nlm.nih.gov

A double-blind randomized placebo controlled trial of thromboprophylaxis in major elective general surgery using once daily injections of a low molecular weight heparin fragment (Fragmin). [2007]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of two regimens of low molecular weight heparin fragment (Fragmin) in preventing postoperative venous thrombolism. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Pre- vs. postoperative initiation of thromboprophylaxis in liver surgery. [2022]