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The human body has a natural stress response to surgery, including the formation of blood clots. This response to surgery has been shown to increase metastases (the spread of cancer cells to other organs in the body). These metastases cannot be seen at the time of surgery but when they grow into new tumors, the cancer has recurred (come back). A blood thinner called "low molecular weight heparin" (LMWH) can suppress the development of metastases after surgery in animal experiments. The investigators want to see if giving patients with colorectal cancer the blood thinner, LMWH, around the time of surgery can decrease the chance of their cancer spreading to other organs (metastases) and coming back (recurrence).
The investigators need 1075 patients to answer our scientific question. Patients who give informed consent will be randomly put into one of two groups, the experimental group and the control group. The patients in the control group will be treated with LMWH starting a few hours after surgery and every day until they leave the hospital. This is how most patients are treated after colon cancer surgery (standard care). The patients in the experimental group will be treated with LMWH for a longer period of time, starting on the day they agree to have surgery and continuing for two months after surgery. All the patients will be followed for at least three years after surgery to find out if their cancer has recurred (come back). If LMWH treatment around the time of surgery reduces the chance of recurrence in patients with colorectal cancer, it would improve the health and quality of life for these patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Extended peri-operative thromboprophylaxis | Experimental | The experimental arm will receive a subcutaneous injection of 4,500 IU of tinzaparin daily beginning at randomization and continued for 56 days following resection. There will be a minimum of one dose of pre-operative LMWH since it is not reasonable to delay surgery for the purpose of administering LMWH. The maximum duration of pre-operative LMWH will be 6 weeks. |
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| Standard thromboprophylaxis | Active Comparator | The control arm will receive a daily subcutaneous injection of 4,500 IU of tinzaparin beginning with the first post-operative dose and continued for the duration of hospitalization. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tinzaparin | Drug | The experimental arm will receive a subcutaneous injection of 4,500 IU of tinzaparin daily beginning at randomization and continued for 56 days following resection. There will be a minimum of one dose of pre-operative LMWH since it is not reasonable to delay surgery for the purpose of administering LMWH. The maximum duration of pre-operative LMWH will be 6 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Free Survival | Disease free survival is measured from the time of randomization until local disease recurrence, distant disease recurrence, a new primary colon cancer malignancy, other second primary cancer or death from any cause. | measured at 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Death from any cause | measured at 5 years |
| Venous Thromboembolism events | • VTE events defined as: a. Deep vein thrombosis: i. non-compressibility of any vein segment from the common femoral vein to the trifurcation of the popliteal vein on compressive ultrasonography ii.persistent intra-luminal filling defect of the iliac, common femoral, superficial femoral, popliteal, posterior tibial or peroneal veins on contrast venography b. Pulmonary embolism: i.high probability V/Q scan ii.positive pulmonary angiogram iii.spiral CT demonstrating intraluminal filling defect in a vessel larger than a segmental artery |
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Inclusion Criteria:
Exclusion Criteria:
Carcinoma only present in a completely excised polyp (i.e. no residual tumour evident in the colon)
Prior VTE including deep vein thrombosis (DVT) or pulmonary embolism (PE)
Requirement for full dose peri-operative anticoagulation
Contraindication to heparin therapy
Participating in another interventional trial that may result in co-intervention or contamination (to be determined by sponsor)
History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years of the colorectal cancer diagnosis
Pregnant or lactating
Unable/unwilling to providing informed consent.
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| Name | Affiliation | Role |
|---|---|---|
| Marc Carrier, MD | Ottawa Hospital Research Institute | Principal Investigator |
| Rebecca Ann Auer, MD | Ottawa Hospital Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ghent University Hospital | Ghent | Belgium | ||||
| Health Sciences North |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36100263 | Derived | Auer RC, Ott M, Karanicolas P, Brackstone MR, Ashamalla S, Weaver J, Tagalakis V, Boutros M, Stotland P, Marulanda AC, Moloo H, Jayaraman S, Patel S, Le Gal G, Spadafora S, MacLellan S, Trottier D, Jonker D, Asmis T, Mallick R, Pecarskie A, Ramsay T, Carrier M; PERIOP-01 investigators. 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. BMJ. 2022 Sep 13;378:e071375. doi: 10.1136/bmj-2022-071375. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Mar 21, 2023 | |
| Reset | Jan 3, 2024 |
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|
|
| Tinzaparin | Drug | The control arm will receive a daily subcutaneous injection of 4,500 IU of tinzaparin beginning with the first post-operative dose and continued for the duration of hospitalization. |
|
|
| From randomization until 56 days post-surgery |
| Major surgical site bleeding events | • Major surgical site bleeding events defined as bleeding at the surgical site associated with:
| From randomization until 56 days post-surgery |
| Major bleeding events (not including the surgical site) | • Major bleeding events (not including the surgical site) defined as:
| From randomization until 56 days post-surgery |
| • Clinically relevant bleeding events prior to surgery and during the • Clinically relevant bleeding events | Clinically relevant bleeding events prior to surgery and during the follow-up period will be defined as overt bleeding episodes not meeting the inclusion for major bleeding but associated with one of the following:
| From randomization to 56 days post-surgery |
| Transfusion requirements | Transfusion requirements using the number of units transfused:
| From randomization to 56 days post-surgery |
| Correlative endpoints | The correlative endpoints seek to evaluate the pro-metastatic mechanisms of surgery and the antimetastatic mechanisms of LMWH in subjects undergoing surgical resection for colon cancer. | 5 years |
| Other post-operative (day 0 - day 28) complications | Other post-operative (day 0 - day 28) complications as defined using the modified Clavien Classification | Measured from Day 0 until day 28 post-operatively |
| Greater Sudbury |
| Ontario |
| Canada |
| Hamilton Health Sciences Corporation | Hamilton | Ontario | L8L 8E7 | Canada |
| Kingston General Hospital | Kingston | Ontario | Canada |
| London Health Research Institute | London | Ontario | N6C 2R5 | Canada |
| The Ottawa Hospital | Ottawa | Ontario | K1H 8L6 | Canada |
| Montfort Hospital | Ottawa | Ontario | Canada |
| Queensway Carleton Hospital | Ottawa | Ontario | Canada |
| Sault Area Hospital | Sault Ste. Marie | Ontario | Canada |
| Humber River Hospital | Toronto | Ontario | M3M 0B2 | Canada |
| Mount Sinai Hospital | Toronto | Ontario | Canada |
| North York General Hospital | Toronto | Ontario | Canada |
| St. Joseph's Health Centre | Toronto | Ontario | Canada |
| Sunnybrook Health Science Centre | Toronto | Ontario | Canada |
| Jewish General Hospital | Montreal | Quebec | Canada |
| CHRU Brest | Brest | France |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Mar 21, 2023 | Jan 3, 2024 |
| ID | Term |
|---|---|
| D003110 | Colonic Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| D000078222 | Tinzaparin |
| ID | Term |
|---|---|
| D006495 | Heparin, Low-Molecular-Weight |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
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