Venous Thromboembolism Prophylaxis Post Cesarean Section (PROCS)

Venous Thromboembolism Prophylaxis Post Cesarean Section(PRO-CS-Trial)

Pregnancy is associated with an overall 5-10 fold increased risk of venous thromboembolism (VTE). VTE remains the most common cause of maternal death in the developed world. It is up to 10 times more common in pregnant women than non-pregnant women of comparable age. More than a third of pregnancy-related VTE occurs during the six weeks after delivery. When compared with vaginal delivery, cesarean delivery further increases the risk of pregnancy associated VTE by three-fold.

Study Overview

• Status: Unknown
• Conditions: Bleeding; Venous Thromboembolism
• Intervention / Treatment: Drug: TINZAPARIN; Drug: PLACEBO

Detailed Description

This is a double blind- a randomized controlled study of prophylactic LMWH in women at low risk for VTE following a cesarean section procedure. The sample size is 300 patients, Eligible, consenting, and randomized participants will receive once-daily injections of study drug (4,500 IU Tinzaparin Sodium [Innohep®] within 12- to 24-hours postpartum and continue for two weeks versus Placebo in the other arm and follow for six (6) weeks postpartum.

On the day of hospital discharge, bilateral leg imaging with compression, leg ultrasounds, and pelvic vein imaging with MRV will be completed. The primary outcome will be adjudicated, while DVT will be documented on ultrasounds or MRV on the day of hospital discharge. Secondary outcomes will include symptomatic DVT and PE, death from PE, major and minor bleeding, and HIT during the six-week postpartum period. All outcomes will be adjudicated by an independent committee of experts blinded to study drug allocation.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia
    • Recruiting
    • Security Forces Hospital
    • Contact: Farjah H AlGahtani, MD; Phone Number: 0505805919; Email: falgahtani@ksu.edu.sa
    • Contact: Pharm
    • Principal Investigator: Farjah H AlGahtani, MD
    • Sub-Investigator: Hessa AlDohami, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Consecutive adult patients (aged over 18 years) that had been delivered by emergency or elective cesarean section with no previous history of VTE are eligible for the study.

Description

Inclusion Criteria:

1. Age > 18 years old.
2. Delivered by cesarean section (emergency or planned).
3. Signed, informed consent.
4. Ready access to a local health service.
5. Capable of using Tinzaparin.

Exclusion Criteria:

1. at high risk for thromboembolism (any one of the following):

   • age more than 35 years old
   • obesity (more than 80 kg)
   • parity more than 4
   • gross varicose veins
   • current infection
   • pre-eclampsia
   • immobility prior to surgery (more than 4 days)
   • Major current disease: including heart or lung disease, cancer,inflammatory bowel disease and nephrotic syndrome.
   • Extended major pelvic or abdominal surgery (e.g. cesarean hysterectomy)
   • Patients with a family history of VTE
   • History of superficial phlebitis
2. More than 36 hours since delivery

3. Need for anticoagulation, including:

   • women with a confirmed thrombophilia
   • women with paralysis of lower limbs
   • women with personal history of VTE
   • women with antiphospholipid antibody syndrome (APLA)
   • women with mechanical heart valves
4. Contraindication to heparin therapy, including history of heparin induced thrombocytopenia.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
STUDY GROUP; will receive the study drug Innohep ® for 14 days	Drug: TINZAPARIN; Eligible women following cesarean section will randomly receive once-daily injections of study drug (4,500 IU tinzaparin sodium within 12 to 24 hours postpartum and continued for two (2) weeks postpartum.; Other Names: Innohep
CONTROL; The group that will receive placebo for 14 days	Drug: PLACEBO; Eligible women following cesarean section will receive a once-daily injections of placebo within 12 to 24 hours postpartum and continued for two (2) weeks postpartum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deep Vein Thrombosis	The primary outcome will be adjudicated, while DVT will be documented on ultrasounds or MRV on the day of hospital discharge.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
symptomatic DVT and bleeding	. Secondary outcomes will include symptomatic DVT and PE, death from PE, major and minor bleeding, and HIT during the six-week postpartum period.	Symptomatic DVT

Collaborators and Investigators

• Sponsor: King Saud University
• Collaborators: King AbdulAziz City for Science and Technology
• Investigators: Principal Investigator: FARJAH H ALGAHTANI, MD, King Saud University

Publications and helpful links

General Publications

• Middleton P, Shepherd E, Gomersall JC. Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period. Cochrane Database Syst Rev. 2021 Mar 29;3(3):CD001689. doi: 10.1002/14651858.CD001689.pub4.
• Kujovich JL. Hormones and pregnancy: thromboembolic risks for women. Br J Haematol. 2004 Aug;126(4):443-54. doi: 10.1111/j.1365-2141.2004.05041.x.
• Samuelsson E, Hellgren M, Hogberg U. Pregnancy-related deaths due to pulmonary embolism in Sweden. Acta Obstet Gynecol Scand. 2007;86(4):435-43. doi: 10.1080/00016340701207500.
• Morris JM, Algert CS, Roberts CL. Incidence and risk factors for pulmonary embolism in the postpartum period. J Thromb Haemost. 2010 May;8(5):998-1003. doi: 10.1111/j.1538-7836.2010.03794.x. Epub 2010 Feb 1.
• Chan WS. Venous thromboembolism in pregnancy. Expert Rev Cardiovasc Ther. 2010 Dec;8(12):1731-40. doi: 10.1586/erc.10.169.

Helpful Links

• Venous Thromboembolism During Pregnancy
• Venous Thromboembolism in Pregnancy Study
• National Guideline Clearinghouse | Venous thromboembolism
• Venous thromboembolism in pregnancy

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Anticipated): January 1, 2013
• Study Completion (Anticipated): January 1, 2013

Study Registration Dates

• First Submitted: March 22, 2011
• First Submitted That Met QC Criteria: March 23, 2011
• First Posted (Estimate): March 24, 2011

Study Record Updates

• Last Update Posted (Estimate): February 6, 2012
• Last Update Submitted That Met QC Criteria: February 3, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: pregnancy; thromboprophylaxis; post-cesarian section
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: PRO-CS TRIAL