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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal timing for starting blood clot prevention treatment (thromboprophylaxis) in individuals undergoing pancreatic surgery. It compares the safety and effectiveness of initiating this treatment before surgery versus after surgery. Participants will receive one of three blood thinners: Enoxaparin, Tinzaparin, or Dalteparin. This trial may suit those planning specific types of pancreatic surgery who are not currently on blood-thinning medications. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and it seeks to understand how it benefits a broader range of patients.

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 is the safety track record for Enoxaparin/Tinzaparin/Dalteparin?

Research has shown that treatments like enoxaparin, tinzaparin, and dalteparin are generally safe for people with pancreatic cancer. One study found that enoxaparin significantly reduced the risk of blood clots from 10.2% to 1.3%. These medications are important for preventing clots. However, a small risk of bleeding exists with these treatments. Specifically, another study found that only 1.9% of patients experienced mild bleeding. While these numbers indicate that the treatments are usually well-tolerated, it is important to be aware of the slight risk involved. Always discuss these risks and benefits with a doctor when considering joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it's exploring the timing of thromboprophylaxis for pancreatic cancer surgery, which could improve patient outcomes. Unlike the standard approach where blood thinners are usually given after surgery to prevent clots, this trial is also testing the effects of starting them before the operation. This could potentially reduce the risk of blood clots even further by addressing clot formation earlier. By comparing preoperative to postoperative administration of drugs like enoxaparin, tinzaparin, and dalteparin, the trial aims to find the optimal timing to maximize safety and effectiveness.

What evidence suggests that this trial's thromboprophylaxis regimens could be effective for pancreatic surgery?

Research has shown that medications like enoxaparin, tinzaparin, or dalteparin can significantly reduce the risk of venous thromboembolism (VTE). In this trial, participants will receive either preoperative thromboprophylaxis, starting these medications before surgery, or postoperative thromboprophylaxis, beginning them after surgery. One study found that enoxaparin reduced the risk of VTE from 10.2% to 1.3% without increasing major bleeding. Another study showed that dalteparin lowered the VTE rate from 23% to 3.4% compared to those who did not receive it. These findings suggest that initiating blood clot prevention before pancreatic surgery can effectively prevent clots, which are common in these patients, without raising the risk of serious bleeding. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10376958/

Venous Thromboembolism and Primary Thromboprophylaxis ... Both trials found thromboprophylaxis to be effective in preventing VTE, without increasing the incidence of major bleeding.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1424390317300650

Efficacy and safety of postoperative anticoagulation ... Thus, there is little evidence of the benefit and safety of enoxaparin after pancreatic surgery. Importantly, no prospective study has focused on the impact of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8228127/

The Impact of Thromboprophylaxis on the Survival ... The impact of thromboprophylaxis on the survival of patients with advanced pancreatic cancer. The pancreatic cancer and tinzaparin (PaCT) study.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.19.01461

Venous Thromboembolism Prophylaxis and Treatment in ... Risk of symptomatic VTE during the first 3 months was 10.2% without enoxaparin and 1.3% with enoxaparin (P = .001). Risk of a major bleed in the ...

5. mdpi.com mdpi.com/1422-0067/25/11/5661

Pancreatic Cancer and Venous Thromboembolism The rate of VTE was significantly lower in the dalteparin arm (3.4% vs. 23% in the control arm, risk ratio 0.145, 95% CI: 0.035–0.612, p = 0.002) [102]. The ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)04786-X/fulltext

Venous thromboembolism in cancer patients There are limited data supporting the efficacy of fondaparinux for VTE prophylaxis in cancer patients undergoing surgery. In a meta-analysis of ...