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Adenocarcinoma of the ColonPhase 3PERIOP-01NCT01455831

Extended Peri-operative Tinzaparin to Improve Disease-free Survival in Patients With Resectable Colorectal Cancer

A Phase 3 study testing Tinzaparin in people with Adenocarcinoma of the Colon, run by Ottawa Hospital Research Institute at 16 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Adenocarcinoma of the Colon
What is being tested?
Tinzaparin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
616 participants
Where
16 sitesin 3 countries
Study dates
Sep 2011to 1 Feb 2021
Phase
Phase 3
Are there results?
None posted in the registry

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

  • Diagnosis of pathologically-confirmed invasive adenocarcinoma of the colon or rectum
  • Pre-operative work-up that reveals potential resectability (CT scan or MRI of the abdomen and pelvis) with resection planned within 6 weeks of date of randomization
  • Pre-operative work-up that reveals no evidence of metastatic disease (CT scan or MRI of the abdomen and pelvis and chest X-ray (CXR) or CT scan of the chest)
  • Age ≥18 years
  • Hemoglobin ≥ 80g/L
  • Able and willing to comply with study procedures and follow-up examinations contained within the written consent form.

Who cannot join

  • 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
  • history of heparin induced thrombocytopenia (HIT)
  • platelet count of less than 100 x 109/L
Show all 16Show fewer
  • actively bleeding
  • severe hypertension (SBP >200 and/or DBP >120) on more than one reading
  • documented peptic ulcer within 6 weeks
  • severe hepatic failure (INR >1.8)
  • creatinine clearance of < 30 ml/min as calculated by the Cockcroft-Gault formula
  • Other contraindication to anticoagulation
  • 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.

Trial locations and contacts

16 sites in 3 countries.

16 sites in 3 countries

Canada14 sites

  • Health Sciences North

    Greater Sudbury, Ontario

  • Hamilton Health Sciences Corporation

    Hamilton, Ontario, L8L 8E7

  • Kingston General Hospital

    Kingston, Ontario

  • London Health Research Institute

    London, Ontario, N6C 2R5

  • Jewish General Hospital

    Montreal, Quebec

  • The Ottawa Hospital

    Ottawa, Ontario, K1H 8L6

  • Montfort Hospital

    Ottawa, Ontario

  • Queensway Carleton Hospital

    Ottawa, Ontario

  • Sault Area Hospital

    Sault Ste. Marie, Ontario

  • Humber River Hospital

    Toronto, Ontario, M3M 0B2

  • Mount Sinai Hospital

    Toronto, Ontario

  • North York General Hospital

    Toronto, Ontario

  • St. Joseph's Health Centre

    Toronto, Ontario

  • Sunnybrook Health Science Centre

    Toronto, Ontario

Other trials in Canada

Belgium1 site

  • Ghent University Hospital

    Ghent

Other trials in Belgium

France1 site

  • CHRU Brest

    Brest

Other trials in France

About this study

Official title: A Multicentre Randomized Controlled Trial of the Use of Extended Peri-Operative Low Molecular Weight Heparin to Improve Cancer Specific Survival Following Surgical Resection of Colorectal Cancer

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.

Being tested
Tinzaparin
Medical subject headings
Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TinzaparinDrug

    Also called Innohep

    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.

  • TinzaparinDrug

    Also called Innohep

    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.

Study groups in NCT01455831
Study groupRoleWhat they receive
Extended peri-operative thromboprophylaxisExperimentalThe 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.
Receives: Drug: Tinzaparin
Standard thromboprophylaxisActive comparatorThe 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.
Receives: Drug: Tinzaparin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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: measured at 3 years

Secondary outcomes (8)

  1. Overall Survival

    Death from any cause

    Measured: measured at 5 years

  2. Venous Thromboembolism events

    • VTE events defined as:
    1. 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

    Measured: From randomization until 56 days post-surgery

  3. Major surgical site bleeding events

    • Major surgical site bleeding events defined as bleeding at the surgical site associated with:
    1. requirement for ≥4 units of packed red blood cells
    2. a drop in Hb of >40 g/L during the first post-op week
    3. bleeding requiring re-operation
    4. fatal bleeding

    Measured: From randomization until 56 days post-surgery

  4. Major bleeding events (not including the surgical site)

    • Major bleeding events (not including the surgical site) defined as:
    1. fatal bleeding, and/or
    2. symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or,
    3. bleeding causing a fall in hemoglobin level of ≥20 g/L, or leading to transfusion of ≥2 units of whole blood or red cells.

    Measured: From randomization until 56 days post-surgery

  5. • 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:

    1. medical intervention;
    2. an unscheduled contact with a physician;
    3. temporary cessation of anticoagulant treatment

    Measured: From randomization to 56 days post-surgery

  6. Transfusion requirements

    Transfusion requirements using the number of units transfused:

    1. Red blood cells
    2. Platelets (Adult dose)
    3. Frozen Plasma

    Measured: From randomization to 56 days post-surgery

  7. 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.

    Measured: 5 years

  8. Other post-operative (day 0 - day 28) complications

    Other post-operative (day 0 - day 28) complications as defined using the modified Clavien Classification

    Measured: Measured from Day 0 until day 28 post-operatively

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2011 (estimated)
  2. Study startSep 2011
  3. Primary completion31 Dec 2020
  4. Study completion1 Feb 2021

Resources

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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
616 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01455831
Sponsor's protocol ID
221097
Acronym
PERIOP-01
Status last verified
May 2021
First submitted
18 Oct 2011
Last updated
17 May 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 36100263

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tinzaparin in people with Adenocarcinoma of the Colon, run by Ottawa Hospital Research Institute at 16 sites in 3 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 6 inclusion and 16 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: finished, as of the sponsor's last update on 17 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Canada, Belgium, France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival (time frame: measured at 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01455831, which also lists 1 linked publication.

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 17 May 2021.

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