Minimally invasive surgery versus open surgery in the treatment of lumbar spondylolisthesis:Study protocol of a multicentre, randomised controlled trial (MISOS trial)

Introduction Patients with symptomatic spondylolisthesis are frequently treated with nerve root decompression, in addition to pedicle screw fixation and interbody fusion. Minimally invasive approaches are gaining attention in recent years, although there is no clear evidence supporting the proclamation of minimally invasive spine surgery (MISS) being better than open surgery. We present the design of the MISOS (Minimal Invasive Surgery versus Open Surgery) trial on the effectiveness of MISS versus open surgery in patients with degenerative or spondylolytic spondylolisthesis. Methods and analysis All patients (age 18-75 years) with neurogenic claudication or radicular leg pain based on low-grade degenerative or spondylolytic spondylolisthesis with persistent complaints for at least 3 months are eligible. Patients will be randomised into mini-open decompression with bilateral interbody fusion with percutaneous pedicle screw fixation (MISS), or conventional surgery with decompression and instrumented fusion with pedicle screws and bilateral interbody fusion (open). The primary outcome measure is Visual Analogue Scale of self-reported low back pain. Secondary outcome measures include improvement of leg pain, Oswestry Disability Index, patients' perceived recovery, quality of life, resumption of work, complications, blood loss, length of hospital stay, incidence of reoperations and documentation of fusion. This study is designed as a multicentre, randomised controlled trial in which two surgical techniques are compared in a parallel group design. Based on a 20 mm difference of low back pain score at 6 weeks (power of 90%, assuming 8% loss to follow-up), a total of 184 patients will be needed. All analyses will be performed according to the intention-to-treat principle. Ethics and dissemination The study has been approved by the Medical Ethical Review Board Southwest Holland in August 2014 (registration number NL 49044.098.14) and subsequently approved by the board of all participating hospitals. Dissemination will include peer-reviewed publications and presentations at national and international conferences

The European Robotic Spinal Instrumentation (EUROSPIN) study: protocol for a multicentre prospective observational study of pedicle screw revision surgery after robot-guided, navigated and freehand thoracolumbar spinal fusion

Introduction Robotic guidance (RG) and computer-assisted navigation (NV) have seen increased adoption in instrumented spine surgery over the last decade. Although there exists some evidence that these techniques increase radiological pedicle screw accuracy compared with conventional freehand (FH) surgery, this may not directly translate to any tangible clinical benefits, especially considering the relatively high inherent costs. As a non-randomised, expertise-based study, the European Robotic Spinal Instrumentation Study aims to create prospective multicentre evidence on the potential comparative clinical benefits of RG, NV and FH in a real-world setting. Methods and analysis Patients are allocated in a non-randomised, non-blinded fashion to the RG, NV or FH arms. Adult patients that are to undergo thoracolumbar pedicle screw instrumentation for degenerative pathologies, infections, vertebral tumours or fractures are considered for inclusion. Deformity correction and surgery at more than five levels represent exclusion criteria. Follow-up takes place at 6 weeks, as well as 12 and 24 months. The primary endpoint is defined as the time to revision surgery for a malpositioned or loosened pedicle screw within the first postoperative year. Secondary endpoints include patient-reported back and leg pain, as well as Oswestry Disability Index and EuroQOL 5-dimension questionnaires. Use of analgesic medication and work status are recorded. The primary analysis, conducted on the 12-month data, is carried out according to the intention-to-treat principle. The primary endpoint is analysed using crude and adjusted Cox proportional hazards models. Patient-reported outcomes are analysed using baseline-adjusted linear mixed models. The study is monitored according to a prespecified monitoring plan. Ethics and dissemination The study protocol is approved by the appropriate national and local authorities. Written informed consent is obtained from all participants. The final results will be published in an international peer-reviewed journal. Trial registration number Clinical Trials.gov registry NCT03398915; Pre-results, recruiting stage

Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial

Background and ObjectivesThe ULTRA trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at 6 months. An expected proportion of the included patients experienced nonaneurysmal subarachnoid hemorrhage. In this post hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at 6 months.MethodsThe ULTRA trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013, and January 20, 2020. After confirmation of subarachnoid hemorrhage on noncontrast CT, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care or usual care only. In this post hoc analysis, we included all ULTRA participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin scale (mRS), dichotomized into good (0-3) and poor (4-6) outcomes.ResultsOf the 813 ULTRA trial patients who experienced an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio [aOR] 0.92; 95% CI 0.69-1.24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) (aOR 0.76; 95% CI 0.57-1.03), all-cause mortality at 30 days (aOR 0.91; 95% CI 0.65-1.28), and all-cause mortality at 6 months (aOR 1.10; 95% CI 0.80-1.52).DiscussionUltra-early and short-term tranexamic acid treatment did not improve clinical outcomes at 6 months in patients with aneurysmal subarachnoid hemorrhage and therefore cannot be recommended.Trial Registration InformationClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013).Classification of EvidenceThis study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage

Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial

BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months. METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812. FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups. INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale. FUNDING: Fonds NutsOhra