Thromboprophylaxis Timing for Pancreatic Cancer Surgery

(PREPOSTEROUS2 Trial)

Recruiting at 4 trial locations

Overseen By Ville Sallinen, MD,PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Helsinki University Central Hospital

Must not be taking: Anticoagulants

Disqualifiers: Emergency operation, Age < 18, others

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

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

Compensation: Varies

Number of Visits: Unknown

800 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently taking anticoagulation medications (blood thinners), you will need to stop them at least 30 days before the surgery to participate in this trial.

What data supports the effectiveness of the drug Enoxaparin/Tinzaparin/Dalteparin for thromboprophylaxis in pancreatic cancer surgery?

Research shows that using tinzaparin with chemotherapy in advanced pancreatic cancer patients increased the time patients lived without the disease getting worse by about 40% compared to those not receiving the drug. Additionally, enoxaparin has been found to be safe and effective in preventing blood clots after pancreatic surgery. ^{1 2 3 4 5}

Is thromboprophylaxis with enoxaparin, tinzaparin, or dalteparin safe for humans?

Studies show that thromboprophylaxis with enoxaparin and tinzaparin is generally safe for humans, with low rates of bleeding and thrombotic events reported in patients undergoing pancreatic surgery or chemotherapy for pancreatic cancer. ^{2 3 4 5 6}

How does the drug enoxaparin/tinzaparin/dalteparin differ from other treatments for pancreatic cancer surgery?

This drug is unique because it is used as a thromboprophylaxis (prevention of blood clots) specifically after pancreatic surgery, which is not commonly reported. It is a low-molecular-weight heparin that helps prevent venous thromboembolic events (blood clots in veins) and has shown to improve progression-free survival in patients with advanced pancreatic cancer when combined with chemotherapy. ^{2 3 5 6 7}

What is the purpose of this trial?

Thromboprophylaxis for pancreatic surgery can be commenced either preoperatively or postoperatively. Despite a clear trade-off between thrombosis and bleeding in pancreatic surgery patients, there is no international consensus when thrombosis prophylaxis should be commenced in patients undergoing pancreatic surgery. 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 pancreatic surgery. On the contrary, Dutch guidelines recommend postoperative thromboprophylaxis only, because of lack of evidence for preoperative thromboprophylaxis. Enhanced Recovery After Surgery (ERAS) Society Guidelines recommend preoperative thromboprophylaxis in pancreatic 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 pancreatic surgery. The aim of this study is to compare pre- and postoperatively initiated thromboprophylaxis regimens in pancreatic surgery in a randomized controlled trial.

Eligibility Criteria

This trial is for patients undergoing pancreatic surgery, specifically pancreaticoduodenectomy or total pancreatectomy for any reason, or distal pancreatectomy due to suspected cancer. It's not suitable for individuals who don't meet these surgical criteria.

Inclusion Criteria

I have had surgery to remove my pancreas or part of it.

I am a patient undergoing treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Thromboprophylaxis

Participants receive thromboprophylaxis before undergoing pancreatic surgery

1 week

Postoperative Thromboprophylaxis

Participants receive thromboprophylaxis after undergoing pancreatic surgery

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Enoxaparin/Tinzaparin/Dalteparin

Trial Overview The study tests whether it's better to start blood clot prevention with drugs like enoxaparin, tinzaparin, or dalteparin before or after pancreatic surgery. This randomized controlled trial aims to provide evidence where current guidelines are unclear.

Participant Groups

Group I: Preoperative thromboprophylaxis Experimental Treatment 1 Intervention

Preoperatively initiated tromboprophylaxis

Group II: Postoperative thromboprophylaxis Active Control 1 Intervention

Postoperatively initiated thromboprophylaxis

Who Is Running the Clinical Trial?

Helsinki University Central Hospital

Lead Sponsor

Trials

449

Recruited

591,000+

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]

In a study of 110 advanced pancreatic cancer patients receiving chemotherapy with nab-paclitaxel and gemcitabine, those who also received tinzaparin for thromboprophylaxis experienced a 39.54% increase in progression-free survival (PFS) compared to those who did not receive anticoagulation, with a median PFS of 7.9 months versus 5.6 months.

The use of tinzaparin was found to be safe, with only 2.7% of patients experiencing thrombotic events and 1.9% experiencing clinically relevant non-major bleeding events during an average follow-up of 18.3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Thromboprophylaxis on the Survival of Patients with Advanced Pancreatic Cancer. The Pancreatic Cancer and Tinzaparin (PaCT) Study. Karamouzis, MV., Athanasiadis, I., Samelis, G., et al.[2021]

In a study of 151 patients who underwent pancreatic surgery, the use of enoxaparin for preventing pulmonary embolism showed no cases of symptomatic pulmonary embolism post-surgery, indicating its efficacy.

The safety profile of enoxaparin was supported by a low incidence of bleeding events (3.3% for both major and minor), with major bleeding largely attributed to non-drug-related complications, suggesting that enoxaparin can be safely used in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of postoperative pharmacologic thromboprophylaxis with enoxaparin after pancreatic surgery. Imamura, H., Adachi, T., Kitasato, A., et al.[2018]

A systematic review of five randomized controlled studies involving 1003 patients with pancreatic cancer showed that primary thromboprophylaxis significantly reduces the risk of venous thromboembolism (VTE) during chemotherapy, with a risk ratio of 0.31 compared to placebo.

The use of thromboprophylaxis did not increase the risk of major bleeding, indicating that it is a safe intervention for preventing VTE in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Frere, C., Crichi, B., Bournet, B., et al.[2020]

In a study of 103 patients undergoing pancreatic resection, enoxaparin was associated with a very low incidence of postoperative venous thromboembolism (VTE), with only 1.9% developing asymptomatic VTE and no cases of symptomatic VTE.

The use of enoxaparin did not lead to an increase in postoperative bleeding complications, with only 2.9% of patients experiencing intra-abdominal hemorrhage, indicating that it is a safe option for thromboprophylaxis in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of postoperative anticoagulation prophylaxis with enoxaparin in patients undergoing pancreatic surgery: A prospective trial and literature review. Hashimoto, D., Nakagawa, S., Umezaki, N., et al.[2022]

A phase IIb study involving 540 patients with advanced pancreatic cancer is investigating the efficacy of enoxaparin, a low molecular weight heparin, in preventing venous thromboembolic events (VTE) during chemotherapy.

An interim analysis of 152 patients showed that enoxaparin did not increase the risk of bleeding compared to no anticoagulation, suggesting it may be a safe option for VTE prevention in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy). Riess, H., Pelzer, U., Hilbig, A., et al.[2022]

In a study investigating the effects of low molecular weight heparins (LMWHs) and fondaparinux on thrombin generation in the presence of pancreatic adenocarcinoma cells, it was found that these anticoagulants primarily inhibit the propagation phase of thrombin generation, which is crucial in managing cancer-related blood clotting issues.

Among the LMWHs tested, tinzaparin was identified as the most effective in inhibiting thrombin generation, outperforming other LMWHs like enoxaparin, nadroparin, and dalteparin, suggesting that specific LMWHs may be better suited for optimizing antithrombotic treatment in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of low molecular weight heparins and fondaparinux upon thrombin generation triggered by human pancreatic cancer cells BXPC3. Gerotziafas, GT., Galea, V., Mbemba, E., et al.[2019]

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. Switzerland pubmed.ncbi.nlm.nih.gov

The Impact of Thromboprophylaxis on the Survival of Patients with Advanced Pancreatic Cancer. The Pancreatic Cancer and Tinzaparin (PaCT) Study. [2021]

3. Japan pubmed.ncbi.nlm.nih.gov

Safety and efficacy of postoperative pharmacologic thromboprophylaxis with enoxaparin after pancreatic surgery. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of postoperative anticoagulation prophylaxis with enoxaparin in patients undergoing pancreatic surgery: A prospective trial and literature review. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy). [2022]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effect of low molecular weight heparins and fondaparinux upon thrombin generation triggered by human pancreatic cancer cells BXPC3. [2019]