Bleeding complications of thromboprophylaxis with dabigatran, nadroparin or rivaroxaban for 6 weeks after total knee arthroplasty surgery: a randomised pilot study.

OBJECTIVES: For the non-vitamin-K oral anticoagulants, data on bleeding when used for 42 days as thromboprophylaxis after total knee arthroplasty (TKA) are scarce. This pilot study assessed feasibility of a multicentre randomised clinical trial to evaluate major and clinically relevant non-major bleeding during 42-day use of dabigatran, nadroparin and rivaroxaban after TKA. PATIENTS AND METHODS: In 70 weeks, between July 2012 and November 2013, 198 TKA patients were screened for eligibility in the Martini Hospital (Groningen, the Netherlands). Patients were randomly assigned to dabigatran (n=45), nadroparin (n=45) or rivaroxaban (n=48). The primary outcome was the combined endpoint of major bleeding and clinically relevant non-major bleeding. Secondary endpoints of this study were the occurrence of clinical venous thromboembolism (VTE) (pulmonary embolism or deep venous thrombosis), compliance, duration of hospital stay, rehospitalisation, adverse events and Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: The primary outcome was observed in 33.3% (95% CI 20.0% to 49.0%), 24.4% (95% CI 12.9% to 39.5%) and 27.1% (95% CI 15.3% to 41.8%) of patients who received dabigatran, nadroparin or rivaroxaban, respectively (p=0.67). Major bleeding was found in two patients who received nadroparin (p=0.21). Clinically relevant non-major bleeding was observed in 33.3% (95% CI 20.0% to 49.0%), 22.2% (95% CI 11.2% to 37.1%) and 27.1% (95% CI 15.3% to 41.8%) for dabigatran, nadroparin and rivaroxaban, respectively (p=0.51). Wound haematoma was the most observed bleeding event. VTE was found in one patient who received dabigatran (p=0.65). The presurgery and postsurgery KOOS qQuestionnaires were available for 32 (71%), 35 (77%) and 35 (73%) patients for dabigatran, nadroparin and rivaroxaban, respectively. KOOS was highly variable, and no significant difference between treatment groups in mean improvement was observed. CONCLUSIONS: A multicentre clinical trial may be feasible. However, investments will be substantial. No differences in major and clinically relevant non-major bleeding events were found between dabigatran, nadroparin and rivaroxaban during 42 days after TKA. KOOS may not be suitable to detect functional loss due to bleeding. TRIAL REGISTRATION NUMBER: NCT01431456.

Pseudotumours, cobalt and clinical outcome in small head metal-on-metal versus conventional metal-on-polyethylene total hip arthroplasty.

BACKGROUND: Metal-on-metal total hip arthroplasty (MoM THA) is associated with the formation of pseudotumours. Studies mainly concern pseudotumour formation in large head MoM THA. We performed a long-term follow-up study, comparing pseudotumour incidence in small head metal-on-metal (SHMoM) THA with conventional metal-on-polyethylene (MoP) THA. Predisposing factors to pseudotumour formation were assessed. METHODS: From a previous randomised controlled trial comparing SHMoM (28 mm) cemented THA with conventional MoP cemented THA, patients were screened using a standardised CT protocol for the presence of pseudotumours. Serum cobalt levels and functional outcome were assessed. RESULTS: 56 patients (33 MoP and 23 MoM) were recruited after mean follow-up of 13.4 years (SD 0.5). The incidence of pseudotumours was 1 (5%) in the SHMoM THA cohort and 3 (9%) in the MoP THA cohort. Prosthesis survival was 96% for both SHMoM and MoP THAs. Serum cobalt levels did not exceed acceptable clinical values (<5 µg/L) whereas no differences in cobalt levels were detected at follow-up between both groups. Oxford and Harris Hip Scores were good and did not differ between SHMoM and MoP THA. CONCLUSIONS: This long-term follow-up study shows a low incidence of pseudotumour formation and good functional outcome in cemented head-taper matched SHMoM and MoP THA.

Direct treatment comparison of DAbigatran and RIvaroxaban versus NAdroparin in the prevention of venous thromboembolism after total knee arthroplasty surgery: design of a randomised pilot study (DARINA).

INTRODUCTION: Two novel agents, dabigatran and rivaroxaban, recently gained market authorisation for prevention of venous thromboembolism (VTE) after hip and knee arthroplasty. However, safety data of the new oral anticoagulants with a long-term use of 42 days are not available for total knee arthroplasty (TKA). Furthermore, there are no clinical trials comparing dabigatran and/or rivaroxaban with nadroparin, which is used in most Dutch departments of orthopaedic surgery. Our aim is to compare the 42-day use of dabigatran and rivaroxaban versus nadroparin after TKA in a clinical explorative pilot study by assessing the incidence of major bleeding and clinically relevant non-major bleeding using a standardised model of bleeding definitions. METHODS AND ANALYSIS: A randomised open-label pilot study was conducted. Patients ≥18 years and weighing more than 40 kg who were scheduled for a primary elective TKA were included. Patients were randomly assigned to three groups. Patients took either a daily oral dose of dabigatran etexilate 220 mg (n=50), 10 mg of oral rivaroxaban (n=50) or subcutaneous nadroparin 0.3 ml (n=50) for 42 days. The primary safety outcome measure was the incidence of bleeding events. Major bleeding events and clinically relevant non-major bleeding events were defined according to accepted guidelines. The secondary measures of this study were the occurrence of VTE, time until the bleeding event, compliance, duration of hospital stay, rehospitalisation, outpatient clinic visits and interventions following complications. Additionally, coagulation monitoring, knee flexion range of motion and Knee injury and Osteoarthritis Outcome Score were evaluated. DISSEMINATION: The results of this trial provided insight into the validity of design for an adequately powered multicentre study investigating the safety of the new oral anticoagulants compared with nadroparin, an anticoagulant applied for prevention of VTE after knee arthroplasty in the Dutch situation. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01431456.

Wear, bone density, functional outcome and survival in vitamin E-incorporated polyethylene cups in reversed hybrid total hip arthroplasty: design of a randomized controlled trial.

BACKGROUND: Aseptic loosening of total hip arthroplasties is generally caused by periprosthetic bone resorption due to tissue reactions on polyethylene wear particles. In vitro testing of polyethylene cups incorporated with vitamin E shows increased wear resistance. The objective of this study is to compare vitamin E-stabilized highly cross-linked polyethylene with conventional cross-linked polyethylene in "reversed hybrid" total hip arthroplasties (cemented all-polyethylene cups combined with uncemented femoral stems). We hypothesize that the adjunction of vitamin E leads to a decrease in polyethylene wear in the long-term. We also expect changes in bone mineral density, less osteolysis, equal functional scores and increased implant survival in polyethylene cemented cups incorporated with vitamin E in the long-term. DESIGN: A double-blinded randomized controlled trial will be conducted. Patients to be included are aged under 70, suffer from non-inflammatory degenerative joint disease of the hip and are scheduled for a primary total hip arthroplasty. The study group will receive a reversed hybrid total hip arthroplasty with a vitamin E-stabilized highly cross-linked polyethylene cemented cup. The control group will receive a reversed hybrid total hip arthroplasty with a conventional cross-linked polyethylene cemented cup. Radiological follow-up will be assessed at 6 weeks and at 1, 3, 5, 7 and 10 years postoperatively, to determine polyethylene wear and osteolysis. Patient-reported functional status (HOOS), physician-reported functional status (Harris Hip Score) and patients' physical activity behavior (SQUASH) will also be assessed at these intervals. Acetabular bone mineral density will be assessed by dual energy X-ray absorptiometry (DEXA) at 6 weeks and at 1 year and 2 years postoperatively. Implant survival will be determined at 10 years postoperatively. DISCUSSION: In vitro results of vitamin E-stabilized polyethylene are promising, showing increased wear resistance. However, controlled clinical follow-up data are not available at this moment.This randomized controlled trial has been designed to determine wear, bone mineral density, functional outcome and survival in reversed hybrid total hip arthroplasty comparing cemented vitamin E-stabilized highly cross-linked polyethylene cups with cemented conventional cross-linked polyethylene cups. TRIAL REGISTRATION: Dutch Trial Registry NTR3049.

Clinical and radiological outcome of conservative vs. surgical treatment of atraumatic degenerative rotator cuff rupture: design of a randomized controlled trial.

BACKGROUND: Subacromial impingement syndrome is a frequently observed disorder in orthopedic practice. Lasting symptoms and impairment may occur when a subsequent atraumatic rotator cuff rupture is also present. However, degenerative ruptures of the rotator cuff can also be observed in asymptomatic elderly individuals. Treatment of these symptomatic degenerative ruptures may be conservative or surgical. Acceptable results are reported for both treatment modalities. No evidence-based level-1 studies have been conducted so far to compare these treatment modalities. The objective of this study is to determine whether there is a difference in outcome between surgical reconstruction and conservative treatment of a degenerative atraumatic rotator cuff tendon rupture. METHODS/DESIGN: A randomized controlled trial will be conducted. Patients aged between 45 and 75 with a symptomatic atraumatic rotator cuff rupture as diagnosed by MRI will be included. Exclusion criteria are traumatic rotator cuff rupture, frozen shoulder and diabetes mellitus. Patients will be randomized into two groups. Conservative treatment includes physical therapy according to a standardized protocol, NSAIDs and, if indicated, subacromial infiltration with a local anesthetic and corticosteroids. Surgical reconstruction is performed under general anesthesia in combination with an interscalenus plexus block. An acromioplasty with reconstruction of the rotator cuff tendon is performed, as described by Rockwood et al. Measurements take place preoperatively and 6 weeks, 3 months, 6 months and 1 year postoperatively. The primary outcome measure is the Constant score. Secondary measures include both disease-specific and generic outcome measures, and an economic evaluation. Additionally, one year after inclusion a second MRI will be taken of all patients in order to determine whether extent and localization of the rupture as well as the amount of fatty degeneration are prognostic factors. DISCUSSION: Both surgical as conservative treatment of a symptomatic atraumatic rotator cuff tendon rupture is used in current practice. There is a lack of level-1 studies comparing surgical vs. conservative treatment. This randomized controlled trial has been designed to determine whether the surgical treatment of a degenerative atraumatic rotator cuff tendon rupture may lead to a better functional and radiological outcome than conservative treatment after one year of follow-up. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR): NTRTC2343.

No superiority of cemented metal-on-metal vs metal-on-polyethylene THA at 5-year follow-up.

A randomized controlled trial was performed to compare the cemented Stanmore metal-on-metal (Biomet, Warsaw, Indiana) total hip arthroplasty (THA; 102 hips) to the cemented Stanmore metal-on-polyethylene (Biomet) THA (98 hips). The primary outcome was clinical performance. Radiological performance, serum cobalt analysis, and prosthetic survival were secondary outcome measures. At a mean follow-up of 5.6 years, 5 patients were lost to follow-up, 18 died, and 4 were revised (3 metal-on- metal, 1 metal-on-polyethylene). Harris Hip Scores improved from 48 to 90 in the metal-on-metal patients (P<.001) and from 46 to 87 in the metal-on-polyethylene patients (P<.001). Oxford Hip Scores changed from 40 to 19 in the metal-on-metal group (P<.001) and from 40 to 18 in the metal-on-polyethylene group (P<.001). For both Harris and Oxford Hip Scores, there was no significant difference between the 2 groups. Five-year survival with revision for any reason was 97% (95% CI 93%-100%) in the metal-on-metal group and 99% (95% CI 97%-100%) in the metal-on-polyethylene group. All revisions were indicated for aseptic loosening (metal-on-metal: 3 cup revisions; metal-on-polyethylene: 1 total revision). At 5-year follow-up, cemented metal-on-metal THA showed no clinical superiority over metal-on-polyethylene THA.