Thromboprophylaxis in Patients Undergoing Orthopedic Surgeries; Comparison Between Rivaroxaban and Enoxaparin

NCT03299296 | Unknown Phase 3 DMC

• 1 other identifier: FW A00015574
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main objective is to reduce the incidence of venous thromboembolism (VTE) in orthopedic postoperative patients based on the potential benefit of using rivaroxaban as a monotherapy. It is around efficacy and safety evaluation of using rivaroxaban as a monotherapy prophylactic agent in patients undergoing orthopedic surgeries taking into the account the reliable selection of patients most benefit. Answering questions about additional cost benefit from the perceptive of the cost-effective analysis on extrapolating the results emerged to our university teaching hospital setting are going to be evaluating as well.

Conditions

Thromboses, Deep Vein; Surgery--Complications

Keywords

Thromboprophylaxis; orthopedic; rivaroxaban; enoxaparin

Outcome Measures

Primary Outcomes (3)

• Any deep-vein thrombosis (DVT)

  Validated clinical prediction rule like Wells Clinical Model is recommended to estimate pretest probability of deep venous thrombosis. Duplex ultrasonography is the preferred test to diagnose deep-vein thrombosis (DVT). Symptoms and signs of DVT may include unilateral leg swelling, pain in the affected leg, calf tenderness in affected leg, increased leg warmth, erythema of affected leg, or a "palpable cord" may be felt in the affected leg. DVT is going to be assessed using Clinical assessment, D-dimer test, Duplex ultrasonography and Venography according to Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines and based on availability and clinical circumstances.

  up to 35 days

• Nonfatal pulmonary embolism (PE)

  Regarding Pulmonary Embolism (PE), diagnosis is suspected in patients with dyspnea, tachypnea, pleuritic chest pain, cough, and/or fever. Diagnosis begins with initial risk stratification "Wells Clinical Model for Evaluating the Pretest Probability of pulmonary embolism (PE) " based on presence of shock or persistent hypotension to identify patients at high risk of early mortality. PE is going to be assessed using Clinical assessment, D-dimer test, Computerized tomography, Ventilation/perfusion (V/Q) scanning and Pulmonary angiography according to American College of Chest Physicians Evidence-Based Clinical Practice Guidelines and based on availability and clinical circumstances.

  up to 35 days

• Death

  Death from any cause including venous thromboembolism

  up to 35 days

Other Outcomes (2)

• Major bleeding risk

  After 4 hours of the first dose and up to 2 days after the last dose of the study drug.

• Other on-treatment bleeding

  After 4 hours of the first dose and up to 2 days after the last dose of the study drug.

Study Arms (2)

Rivaroxaban arm

EXPERIMENTAL

Rivaroxaban 10 Milligrams

Drug: Rivaroxaban 10 Milligrams

Enoxaparin Arm

ACTIVE COMPARATOR

'Enoxaparin 40 Milligrams /0.4 Milliliters Prefilled Syringe

Drug: Enoxaparin 40 Milligrams/0.4 Milliliters Prefilled Syringe

Interventions

Rivaroxaban 10 Milligrams DRUG

The first group is to be on Rivaroxaban 10 mg with dosage according to the orthopedic approved regimen (10 mg once daily 6-10 hours after the surgery; recommended total duration of therapy: 12 to 14 days; The American College of Chest Physicians (ACCP) recommendation: Minimum of 10 to 14 days; extended duration of up to 35 days suggested.

Rivaroxaban arm

Enoxaparin 40 Milligrams/0.4 Milliliters Prefilled Syringe DRUG

The other group will be administered the standard of care (SOC) enoxaparin as follows: Once-daily dosing: 40 mg once daily, with initial dose within 9 to 15 hours before surgery, and daily for at least 10 days (or up to 35 days postoperatively) or until risk of deep venous thrombosis (DVT) has diminished or the patient is adequately anticoagulated on warfarin. The American College of Chest Physicians recommends initiation ≥12 hours preoperatively or ≥12 hours postoperatively; extended duration of up to 35 days suggested.

Enoxaparin Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Undergo Orthopedic Surgery
• Thromboprophylaxis Decision Taken
• At least 18 years of age

You may not qualify if:

• Planned intermittent pneumatic compression
• A requirement for anticoagulant therapy that could not be stopped
• Severe hypersensitivity reaction (eg, anaphylaxis) to rivaroxaban or enoxaparin.
• Received another anticoagulant for more than 24 hours
• Active bleeding or a high risk of bleeding
• Thrombocytopenia associated with a positive test for antiplatelet antibody.
• Warfarin associated international normalized ratio (INR) more than 1.5 on the day of the surgery
• Conditions preventing bilateral venography
• Intensive care unit (ICU) stay after surgery
• Pregnant or breast-feeding
• Creatinine clearance less than 30 ml per minute or acute renal failure before the surgery or at any point during the study period.
• Moderate or Severe (Child Pugh B or C) hepatic Impairment or in patients with any hepatic disease associated with coagulopathy.
• Concomitant use of drugs that are both P--glycoprotein inhibitors and moderate to strong cyp3a4 (ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir \& conivaptan)
• Creatinine clearance (CrCl) 15 to 80 mL/min and concurrent use of P-glycoprotein inhibitors or moderate CYP3A4 inhibitors (eg, abiraterone acetate, diltiazem, dronedarone, erythromycin, verapamil)

Sponsors & Collaborators

• Ahmed AbdelMoneim Hassan Ali: lead
• Beni-Suef University: collaborator

Related Publications (6)

• Beyer-Westendorf J, Lutzner J, Donath L, Tittl L, Knoth H, Radke OC, Kuhlisch E, Stange T, Hartmann A, Gunther KP, Weiss N, Werth S. Efficacy and safety of thromboprophylaxis with low-molecular-weight heparin or rivaroxaban in hip and knee replacement surgery: findings from the ORTHO-TEP registry. Thromb Haemost. 2013 Jan;109(1):154-63. doi: 10.1160/TH12-07-0510. Epub 2012 Nov 29.

  PMID: 23197272 BACKGROUND

• Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuunemann HJ; American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):7S-47S. doi: 10.1378/chest.1412S3. No abstract available.

  PMID: 22315257 BACKGROUND

• Lassen MR, Gent M, Kakkar AK, Eriksson BI, Homering M, Berkowitz SD, Turpie AG. The effects of rivaroxaban on the complications of surgery after total hip or knee replacement: results from the RECORD programme. J Bone Joint Surg Br. 2012 Nov;94(11):1573-8. doi: 10.1302/0301-620X.94B11.28955.

  PMID: 23109641 BACKGROUND

• Granero J, Diaz de Rada P, Lozano LM, Martinez J, Herrera A; en nombre de los investigadores del grupo XAMOS Espana. [Rivaroxaban versus standard of care in venous thromboembolism prevention following hip or knee arthroplasty in daily clinical practice (Spanish data from the international study XAMOS)]. Rev Esp Cir Ortop Traumatol. 2016 Jan-Feb;60(1):44-52. doi: 10.1016/j.recot.2015.05.009. Epub 2015 Jul 17. Spanish.

  PMID: 26194908 BACKGROUND

• Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e419S-e496S. doi: 10.1378/chest.11-2301.

  PMID: 22315268 BACKGROUND

• Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, Gibbs JS, Huisman MV, Humbert M, Kucher N, Lang I, Lankeit M, Lekakis J, Maack C, Mayer E, Meneveau N, Perrier A, Pruszczyk P, Rasmussen LH, Schindler TH, Svitil P, Vonk Noordegraaf A, Zamorano JL, Zompatori M; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014 Nov 14;35(43):3033-69, 3069a-3069k. doi: 10.1093/eurheartj/ehu283. Epub 2014 Aug 29. No abstract available.

  PMID: 25173341 BACKGROUND

MeSH Terms

Conditions

Venous Thrombosis

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Ahmed AH Hassan Ali, master

  School of Pharmacy Beni Suef University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Lecturer of Clinical Pharmacy

Model Details: single blind, sequentially simple randomized controlled clinical trial

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: October 3, 2017
• Study Start: January 1, 2017
• Primary Completion: January 30, 2018
• Study Completion: March 30, 2018
• Last Updated: October 17, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: within the study period and after finishing it.
• Access Criteria: upon any request from Faculty of Medicine Beni Suef University Research Ethical Committee at any time of the study period, the hard cover of any documented will be delivered by hand to the Chairperson of the committee