15 research outputs found
individual participant data meta-analysis of randomised trials study protocol
Introduction Parenteral anticoagulants may improve outcomes in patients with
cancer by reducing risk of venous thromboembolic disease and through a direct
antitumour effect. Study-level systematic reviews indicate a reduction in
venous thromboembolism and provide moderate confidence that a small survival
benefit exists. It remains unclear if any patient subgroups experience
potential benefits. Methods and analysis First, we will perform a
comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library,
hand search scientific conference abstracts and check clinical trials
registries for randomised control trials of participants with solid cancers
who are administered parenteral anticoagulants. We anticipate identifying at
least 15 trials, exceeding 9000 participants. Second, we will perform an
individual participant data meta-analysis to explore the magnitude of survival
benefit and address whether subgroups of patients are more likely to benefit
from parenteral anticoagulants. All analyses will follow the intention-to-
treat principle. For our primary outcome, mortality, we will use multivariable
hierarchical models with patient-level variables as fixed effects and a
categorical trial variable as a random effect. We will adjust analysis for
important prognostic characteristics. To investigate whether intervention
effects vary by predefined subgroups of patients, we will test interaction
terms in the statistical model. Furthermore, we will develop a risk-prediction
model for venous thromboembolism, with a focus on control patients of
randomised trials. Ethics and dissemination Aside from maintaining participant
anonymity, there are no major ethical concerns. This will be the first
individual participant data meta-analysis addressing heparin use among
patients with cancer and will directly influence recommendations in clinical
practice guidelines. Major cancer guideline development organisations will use
eventual results to inform their guideline recommendations. Several knowledge
users will disseminate results through presentations at clinical rounds as
well as national and international conferences. We will prepare an evidence
brief and facilitate dialogue to engage policymakers and stakeholders in
acting on findings. Trial registration number PROSPERO CRD4201300352
Peripartum hyperhemolysis prophylaxis and management in sickle cell disease: A case report and narrative review.
BACKGROUND: Sickle cell disease (SCD) is associated with hematologic complications including delayed hemolytic transfusion reactions (DHTRs) and pregnancy-related morbidity and mortality. Hyperhemolysis syndrome (HS) is the most severe form of DHTR in patients with SCD, in which both transfused and native red blood cells are destroyed. Further transfusions are avoided after a history of HS. Immunosuppressive agents can be used as prophylaxis against life-threatening hemolysis when transfusion is necessary. There is a paucity of evidence for the use of HS prophylaxis before transfusions, the continuation of hydroxyurea (HU) in lieu of chronic transfusion, and the use of erythropoiesis-stimulating agents (ESA) in pregnant SCD patients.
CASE REPORT: We present a case of a pregnant patient with SCD and a previous history of HS. HS prophylaxis was given before transfusion with corticosteroids, intravenous immunoglobulin, and rituximab. In addition, HU was continued during pregnancy to control SCD, along with the use of concomitant ESA to maintain adequate hemoglobin levels and avoid transfusion. We describe a multidisciplinary approach to pregnancy and delivery management including tailored anesthetic and obstetric planning.
CONCLUSION: This is the first published case of HS prophylaxis in a pregnant SCD patient, with good maternal and fetal outcomes after transfusion. HU and ESAs were able to control SCD and mitigate anemia in lieu of prophylactic transfusions during pregnancy. Further prospective studies are necessary to elucidate the ideal management of pregnant SCD patients with a history of HS or other contraindications to chronic transfusion
THromboprophylaxis In Sickle Cell Disease with central venous catheters (THIS): an internal pilot randomised controlled trial protocol
Introduction Individuals with sickle cell disease (SCD) and central venous catheters (CVC) are at high risk for venous thromboembolism (VTE). Minimal data exist regarding the use of anticoagulation as thromboprophylaxis of VTE in this demographic, and as a result, clinical equipoise exists. Prophylactic dose rivaroxaban, a direct oral anticoagulant, is efficacious and safe as thromboprophylaxis in other demographics, and may be an optimal agent in SCD with CVC. Prior to conducting a full clinical trial to assess rivaroxaban as thromboprophylaxis in SCD with CVC, a pilot study is needed to gauge its feasibility.Methods and analysis THromboprophylaxis In Sickle Cell Disease pilot trial is an investigator-initiated, multicentre, double-blinded, randomised controlled trial (RCT) assessing if it is feasible and safe to conduct an adequately powered RCT comparing rivaroxaban to matching placebo as thromboprophylaxis in those with SCD and CVC. Fifty adult patients with SCD and CVC will be randomised to receive either rivaroxaban 10 mg daily or matching placebo for the duration of the CVC in situ for up to 1 year. After randomisation, follow-up visits will occur every 3 months. The primary outcomes pertain to the feasibility of a full trial and include numbers of eligible and recruited participants. Exploratory outcomes include overall incidence of VTE and bleeding complications, as well as quality of life. If the full trial is feasible, blinding will be maintained and patients in the pilot study will be included in the full trial.Ethics and dissemination The trial was initially approved by the University Health Network Research Ethics Board (REB) in Toronto, Canada. All sites will obtain approval from their respective REB prior to commencement of study activities. Study results will be disseminated through presentations at medical conferences and peer-reviewed publications.Trial registration number NCT05033314
An individual participant data meta-analysis of 13 randomized trials to evaluate the impact of prophylactic use of heparin in oncological patients
Background: Parenteral anticoagulants may improve outcomes in patients with cancer by reducing the risk of venous thromboembolism (VTE) and through a direct anti-tumour effect. Study-level meta-analysis indicates a reduction in VTE and provide moderate certainty that a small survival benefit exists; it is unclear if patients with specific cancers benefit more or less. Utilizing data from randomized controlled trials (RCT), this individual participant data meta-analysis examines the impact of heparin on survival, VTE and major bleeding in oncological patients randomized to low-molecular weight heparin (LMWH) or no LMWH
The Khorana Score for the prediction of venous thromboembolism in patients with solid cancer: An individual patient data meta-analysis
Background: Guidelines suggest the use of the Khorana score to select patients with solid cancer receiving chemotherapy for thromboprophylaxis to prevent venous thromboembolism (VTE), but its performance in different types of cancers remains uncertain