Oral anticancer medicine interventions: A cross-sectional study in French community pharmacies.

INTRODUCTION: The increasing number of oral anticancer medicines (OAMs) dispensed in community pharmacies and the associated challenges (misuse, management of side effects) give the community pharmacist (CP) a major role in the pharmacotherapeutic management of cancer patients. In France, as a response to these challenges, cancer outpatients can schedule a meeting with their CP to ensure the safe and effective use of OAMs. The objectives of this study were to evaluate the perspectives of these interventions regarding their implementation and the opinion of French CPs. METHODS: A declarative survey and semi-structured interviews were conducted with CPs that dispensed at least one OAM between January 2021 and March 2022. The study was conducted between April and August 2022. RESULTS: Eighty-five CPs completed the survey. Of these pharmacists, 21% (n = 18) had already performed OAM interventions and 91% (n = 61) wanted to implement them. Lack of time, knowledge and training were the main barriers to implementation. No correlations were identified between the characteristics of community pharmacies and the likelihood of implementing OAM interventions. CONCLUSIONS: Considering that CPs seem willing to implement them and the favourable context in France, this observational study highlights the potential of OAM interventions to improve the management of cancer patients. Though further studies are required to better evaluate the implementation and the potential effects of these interventions, OAM interventions could be relevant strategies in other healthcare systems to secure the management of cancer patients through the involvement of the CP.

Benefit of a flash dose of corticosteroids in digestive surgical oncology: a multicenter, randomized, double blind, placebo-controlled trial (CORTIFRENCH).

BACKGROUND: The modulation of perioperative inflammation seems crucial to improve postoperative morbidity and cancer-related outcomes in patients undergoing oncological surgery. Data from the literature suggest that perioperative corticosteroids decrease inflammatory markers and might be associated with fewer complications in esophageal, liver, pancreatic and colorectal surgery. Their benefit on cancer-related outcomes has not been assessed. METHODS: The CORTIFRENCH trial is a phase III multicenter randomized double-blind placebo-controlled trial to assess the impact of a flash dose of preoperative corticosteroids versus placebo on postoperative morbidity and cancer-related outcomes after elective curative-intent surgery for digestive cancer. The primary endpoint is the frequency of patients with postoperative major complications occurring within 30 days after surgery (defined as all complications with Clavien-Dindo grade > 2). The secondary endpoints are the overall survival at 3 years, the disease-free survival at 3 years, the frequency of patients with intraabdominal infections and postoperative infections within 30 days after surgery and the hospital length of stay. We hypothesize a reduced risk of major complications and a better disease-survival at 3 years in the experimental group. Allowing for 5% of drop-out, 1 200 patients (600 per arm) should be included. DISCUSSION: This will be the first trial focusing on the impact of perioperative corticosteroids on cancer related outcomes. If significant, it might be a strong improvement on oncological outcomes for patients undergoing surgery for digestive cancers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03875690, Registered on March 15, 2019, URL: https://clinicaltrials.gov/ct2/show/NCT03875690 .

Potentially inappropriate medications and anticholinergic and sedative burden in older patients with haemophilia or von Willebrand disease: The M'HEMORRH-AGE study.

WHAT IS KNOWN AND OBJECTIVE: In older patients, multiple chronic conditions lead to the intake of multiple medications and a higher risk of adverse drug events. The exposure to inappropriate medications in older patients with bleeding disorders is poorly explored. The aim of this study was to describe the exposure to potentially inappropriate medications (PIMs) and medications with anticholinergic and sedative properties in older community-dwelling patients with haemophilia or von Willebrand Disease (VWD). METHODS: The M'HEMORRH-AGE study (Medication in AGEd patients with HAEMORRHagic disease) is a multicentre prospective observational study. Community-dwelling patients over 65 years with haemophilia or VWD were included in the study. PIMs were identified using the EU(7)-PIM list, and the anticholinergic and sedative drug exposure was measured using the Drug Burden Index. RESULTS AND DISCUSSION: 142 older community-dwelling patients with haemophilia (n = 89) or VWD (n = 53) were included (mean age: 72.8 ± 5.8 years). PIMs were used by 45.8% of older patients and were mainly represented by cardiovascular (34.9%), nervous systems (26.7%) and alimentary tract and metabolism PIMs (25.6%). Regarding anticholinergic and/or sedative medications, 37.3% of older patients were exposed mainly due to nervous system medications (68.3%), for example analgesics. WHAT IS NEW AND CONCLUSION: The M'HEMORRH-AGE study showed the exposure to PIMs and anticholinergic/sedative medications was high in older community-dwelling patients with haemophilia or VWD. Interventions focusing on deprescription of these inappropriate medications should be conducted in this specific population.

Self-management of immunomodulatory drug treatment in multiple myeloma patients.

OBJECTIVE: Immunomodulatory drugs (IMIDs: thalidomide, lenalidomide and pomalidomide) are widely used in patients with multiple myeloma (MM). The aim of our study was to validate a questionnaire to evaluate the self-capacity of MM patients to manage IMID treatment including side effects. METHODS: We used a method adapted from the recommendations of the European Organisation for Research and Treatment of Cancer (EORTC) to validate a French questionnaire for patients with MM treated with IMIDs. RESULTS: The face validity was evaluated in 15 patients and the construct validity in 56 patients. For discriminant validity, two groups were constituted by gender and depending on whether they had a previous IMID treatment. The median questionnaire score was 11.33/16 (IQR 9.75-12.08) with a minimum of 5.2 and a maximum of 14.75. For discriminant validity, a statistically significant difference was observed for patient capacity to contact healthcare professionals in specific situations and drug intake in case of swallowing disorder. Convergent validity showed an acceptable reliability for the scores of the different questions. CONCLUSION: The questionnaire has shown to be a valid tool for the assessment of the adherence and side-effect management skills for MM patients with IMID treatment.

Safety of ninety-minute daratumumab infusion.

PURPOSE: Daratumumab is the first anti-CD38 monoclonal antibody of the class approved for recurrent and refractory multiple myeloma. Grade 3 and 4 Infusion-Related Reactions (IRRs) are frequent during the first and second infusions. Due to the risks associated with severe IRRs, daratumumab is systematically administered over a period of 3.5 hours.The main objective of this study was to evaluate the safety of a 90-minute daratumumab infusion from the third infusion. PATIENTS AND METHODS: All patients who had received two or more doses of daratumumab in monotherapy or in combination with standard infusion rates were included. We excluded patients enrolled in clinical trials. For the rapid infusion protocol, 20% of the dose was administered over 30 minutes and the remaining 80% over 60 minutes. RESULTS: From April 1 to May 31, 2019, 25 patients received 53 90-minute infusions of daratumumab. Premedication included corticosteroids, antipyretics, antihistamines, and if necessary a leukotriene receptor antagonist. No grade 3 or grade 4 IRRs were observed. CONCLUSION: From the third infusion, we found that a rapid administration of daratumumab (90 vs 210 minutes) was well tolerated and safe. It would be interesting to test this regimen from the second infusion.

[Patients treated with anticancer drugs: Practices and expectations of community pharmacists]. / Patients sous anticancéreux : pratiques et attentes des pharmaciens officinaux.

INTRODUCTION: The evolution of pharmacotherapeutic management of cancer patients makes essential the role of the community pharmacist through its management conducted in community pharmacy as well as its relationships with the hospital and primary care professionals. The objective of this work is to study this pharmacotherapeutic management, for all routes of administration considered. METHODS: This observational study is based on a questionnaire and semi-structured interviews conducted with community pharmacists in contact with the Unité médicale ambulatoire de cancérologie (UMAC) of the University Hospital of Dijon. RESULTS: The main objective of community pharmacists is to ensure that patients understand and comply with their treatment. Twenty-one percent of them have already implemented oral anticancer drug interviews. Sixty-five percent have partial information about the injectable treatments administered to their patients while only 3 % have complete knowledge. Sixty-nine percent of community pharmacists are satisfied with the documents sent by the UMAC (summary of drug treatments, pharmaceutical report, individualized pharmaceutical plan). However, the lack of information from hospital structures generally represents one of the main difficulties in the management of cancer patients by community pharmacists and coordination with other professionals. DISCUSSION: The information and training of community pharmacists represent possible improvements for a better care and coordination between healthcare professionals. Some emerging practices, such as the implementation of oral anticancer drug interviews in community pharmacies and the participation of community pharmacists in primary care coordination organizations, also represent opportunities to strengthen their role in the management of cancer patients.

Systematic review of locking solutions for non-tunneled hemodialysis catheters.

BACKGROUND: We conducted a systematic review of studies investigating lock solutions for use in non-tunneled hemodialysis catheters. METHODS: We searched PubMed and Cochrane databases from inception to June 11, 2021. Study inclusion criteria were: randomized trial or observational study, adults (>18 years), with acute kidney injury (AKI); and temporary non-tunneled catheters. We recorded bleeding events, catheter dysfunction and complications. RESULTS: Of 649 studies identified, 6 were included (4 randomized, 1 non-randomized trial, 1 retrospective cohort study; sample sizes 78-1496 patients). Citrate was compared to heparin in 4 studies, to saline in 1, and ethanol versus saline in 1. Event-free survival of non-tunneled catheters did not differ between groups. Catheter-related infections and adverse events were less frequent with citrate locks, but reached statistical significance in only two studies. CONCLUSION: Existing data are too heterogeneous to enable recommending one type of catheter lock over any other for non-tunneled hemodialysis catheters.

Polypharmacy and medication regimen complexity in older patients with hemophilia or von willebrand disease: the M'HEMORRH-AGE study.

BACKGROUND: In older patients, multiple chronic conditions lead topolypharmacy which is associated with a higher risk of adverse drug events. Nowadays, the medication exposure of older patients with bleeding disorders has been poorly explored. AIM: The aim of this study was to assess the prevalence of polypharmacy and the medication regimen complexity in older community-dwelling patients with hemophilia or von Willebrand Disease (VWD). METHOD: The M'HEMORRH-AGE study (Medication in AGEd patients with HEMORRHagic disease) is a multicenter prospective observational study. Community-dwelling patients over 65 years with hemophilia or VWD were included in the study. The rate of polypharmacy (use of 5 to 9 drugs daily) and excessive polypharmacy (use of 10 or more medications daily) was assessed. The complexity of prescribed medication regimens was assessed using the Medication Regimen Complexity Index (MRCI). RESULTS: Overall, 142 older community-dwelling patients with hemophilia (n = 89) or VWD (n = 53) were included (mean age: 72.8 (5.8) years). Prevalence of polypharmacy and excessive polypharmacy were 40.8% and 17.6%, respectively. The mean MRCI score was 16.9 (6.1). The mean MRCI score related to bleeding disorders medications was 6.9 (1.1). There was no significant difference between older hemophilia patients and VWD patients. CONCLUSION: The M'HEMORRH-AGE study showed that more than half of older community-dwelling patients were affected by polypharmacy. In addition, the high medication regimen complexity in this older population suggests that interventions focusing on medication review and deprescribing should be conducted to reduce polypharmacy with its negative health-related outcomes.

Dexmedetomidine to reduce vasopressor resistance in refractory septic shock: Protocol for a double-blind randomized controlled pilot trial (ADRESS Pilot study).

Introduction: Refractory septic shock (RSS) is characterized by high vasopressor requirements, as a consequence of vasopressor resistance, which may be caused or enhanced by sympathetic hyperactivation. Experimental models and clinical trials show a reduction in vasopressor requirements and improved microcirculation compared to conventional sedation. Dexmedetomidine did not reduce mortality in clinical trials, but few septic shock patients were enrolled. This pilot trial aims to evaluate vasopressor re-sensitization with dexmedetomidine and assess the effect size, in order to design a larger trial. Methods: This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, comparing dexmedetomidine versus placebo in RSS patients with norepinephrine dose ≥0.5µg/kg/min. The primary outcome is blood pressure response to phenylephrine challenge, 6 hours after completion of a first challenge, after study treatment initiation. Secondary outcomes include feasibility and safety outcomes (bradycardia), mortality, vasopressor requirements, heart rate variability, plasma and urine catecholamines levels. The sample size is estimated at 32 patients to show a 20% improvement in blood pressure response to phenylephrine. Randomization (1:1) will be stratified by center, sedation type and presence of liver cirrhosis. Blood pressure and ECG will be continuously recorded for the first 24 h, enabling high-quality data collection for the primary and secondary endpoints. The study was approved by the ethics committee "Sud-Est VI" (2019-000726-22) and patients will be included after informed consent. Discussion: The present study will be the first randomized trial to specifically address the hemodynamic effects of dexmedetomidine in patients with septic shock. We implement a high-quality process for data acquisition and recording in the first 24 h, ensuring maximal quality for the evaluation of both efficacy and safety outcomes, as well as transparency of results. The results of the study will be used to elaborate a full-scale randomized controlled trial with mortality as primary outcome in RSS patients. Trial registration: Registered with ClinicalTrials.gov (NCT03953677). Registered 16 May 2019, https://clinicaltrials.gov/ct2/show/NCT03953677.

Smoking in Patients With Chronic Cardiovascular Disease During COVID-19 Lockdown.

Objectives: This cross-sectional study aims to investigate health-related behaviors including tobacco consumption among patients with cardiovascular diseases (CVD), during the first COVID-19-related lockdown. Methods: After 5 weeks of COVID-19 lockdown, 220 patients with chronic coronary syndromes (CCS) and 124 with congestive heart failure (CHF) answered a phone questionnaire. Results: Among these 344 patients, 43 (12.5%) were current smokers, and none had quit during the lockdown. When compared with non-smokers, smokers were 15 years younger, more often diabetic, more likely to live in an urban than a rural lockdown location, and more often in the CCS cohort (p = 0.011). Smokers described greater psychological impairment, but their rates of decrease in physical activity and of increase in screen time were similar to non-smokers. More than one-third (13/43) increased their tobacco consumption, which was mainly related to stress or boredom, but not driven by media messages on a protective effect of nicotine. Conclusions: During the first COVID-19 lockdown, we found a decrease in favorable lifestyle behaviors among patients with CVD. Strikingly, one-third of smokers with CCS or CHF increased their tobacco consumption. Given the major impact of persistent smoking in patients with CVD, this highlights the need for targeted prevention strategies, in particular during such periods.

Association between proton pump inhibitors and severe hematological toxicity in patients receiving pemetrexed-based anticancer treatment: The prospective IPPEM study.

OBJECTIVE: Pemetrexed is associated with hematological toxicity. Drug-drug interactions (DDIs) between methotrexate and proton pump inhibitors (PPIs) induce a higher risk of hematological toxicity due to the inhibition of methotrexate excretion by PPIs. As pemetrexed and methotrexate are both excreted by human organic anion transporter 3 (hOAT3), this study investigates the hypothetical DDI between pemetrexed and PPIs in lung cancer patients. The primary objective was the occurrence of severe (grade ≥ 3) hematological toxicity. The secondary objectives were to describe the type of hematological toxicity and associated clinical consequences (NCT03537833). MATERIALS AND METHODS: PPI consumption was collected for each patient receiving pemetrexed-based anticancer chemotherapy from May 2018 to October 2020 in a prospective multicentric observational and nonrandomized study. Multivariate Cox regression and propensity score (PS) adjustment, PS matching and inverse weighting on PS (IPTW) methods were used. RESULTS: PPI consumption (55 among 156 included patients) was associated with a significantly higher risk of severe hematological toxicity in the multivariable Cox regression model (hazard ratio HR = 2.51, 95% confidence interval [1.47-4.26]; p = 0.005). Similar results were found with PS adjustment (HR = 1.91 CI95% [1.14-3.20]; p = 0.002), PS-matching (HR = 1.93 CI95% [1.08-3.45]; p = 0.02) and IPTW method (HR = 2.06 CI95% [1.27-3.35]; p = 0.004). Severe neutropenia and anemia occurred in 32.7% and 14.1% of patients, respectively. This resulted in 48 anticancer chemotherapy postponements and 24 dose adjustments, 26 growth factor prescriptions, 24 red blood cell transfusions, and 20 hospitalizations. CONCLUSIONS: The results strongly suggest an association between PPI consumption and pemetrexed-related severe hematological toxicity. Deprescription of PPIs when feasible should be considered to prevent this DDI.

Remdesivir for Patients Hospitalized with COVID-19 Severe Pneumonia: A National Cohort Study (Remdeco-19).

BACKGROUND: Given the rapidly evolving pandemic of COVID-19 in 2020, authorities focused on the repurposing of available drugs to develop timely and cost-effective therapeutic strategies. Evidence suggested the potential utility of remdesivir in the framework of an early access program. REMDECO-19 is a multicenter national cohort study assessing the ability of remdesivir to improve the outcome of patients hospitalized with COVID-19. METHODS: We conducted a retrospective real-life study that included all patients from the early access program of remdesivir in France. The primary endpoint was the clinical course evolution of critically ill and hospitalized COVID-19 patients treated with remdesivir. Secondary endpoints were the SOFA score evolution within 29 days following the admission and mortality at 29 and 90 days. RESULTS: Eighty-five patients were enrolled in 22 sites from January to April 2020. The median WHO and SOFA scores were respectively reduced by two and six points between days 1 and 29. Improvement in the WHO-CPS and the SOFA score were observed in 83.5% and 79.3% of patients, respectively, from day 10. However, there was no effect of remdesivir on the 90-day survival based on the control cohort for hospitalized COVID-19 patients with invasive ventilation. CONCLUSIONS: SOFA score appeared to be an attractive approach to assess remdesivir efficacy and stratify its utilization or not in critically ill patients with COVID-19. This study brings a new clinical benchmark for therapeutic decision making and supports the use of remdesivir for some hospitalized COVID-19 patients.

Levosimendan in venoarterial ECMO weaning. Rational and design of a randomized double blind multicentre trial.

AIMS: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used in circulatory failure. The main indications are cardiogenic shock, post-cardiotomy cardiac failure, and refractory cardiac arrest. However, VA-ECMO weaning is particularly challenging, and weaning failure is reported to be as high as 50%, with increased related mortality. Levosimendan is a novel long acting effect inodilator used in cardiogenic shock and terminal heart failure decompensation. Levosimendan use in VA-ECMO patients seems to reduce weaning failure regardless of the initial aetiology and to reduce mortality when administrated early after VA-ECMO initiation. However, studies are limited to retrospective analyses and reported case series. The aim of the WEANILEVO trial is to evaluate whether administration of levosimendan before VA-ECMO weaning is associated with a reduced rates of weaning failure and recourse to other temporary circulatory support. METHODS AND RESULTS: WEANILEVO is a randomized, prospective, multicentre, double-blind, parallel-group, controlled trial. One hundred eighty patients will be enrolled if they had acute circulatory heart failure treated with VA-ECMO and for whom weaning is expected within 48 h. The study drugs are either levosimendan (0.2 µg/kg/min for 24 h) or a placebo. The primary endpoint of the trial is the absence of VA-ECMO weaning, recourse to another VA-ECMO, or other temporary circulatory assistance or death within 7 days of VA-ECMO weaning. CONCLUSIONS: Levosimendan use in VA-ECMO appears to be beneficial for reducing weaning failure and mortality. The results of WEANILEVO should significantly influence decisions regarding the use of levosimendan for VA-ECMO weaning.

Adherence to immunomodulatory drugs in patients with multiple myeloma.

BACKGROUND: Immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide; IMID) are widely used in the treatment of multiple myeloma patients. To date, few data are available on IMID adherence in multiple myeloma patients. The aim of our study was to evaluate IMID adherence and to compare two indirect methods to measure IMID adherence in multiple myeloma patients: a specific questionnaire and the medication possession ratio (MPR). Another aim was to explore this specific questionnaire for the assessment of IMID adherence in multiple myeloma patients. METHODS: All consecutive multiple myeloma patients, with at least two consecutive dispensations of thalidomide, lenalidomide or pomalidomide in our hospital were included in this prospective study. IMID adherence was measured using a specific questionnaire and the medication possession ratio. Relationship between the questionnaire scores and variables of interest was evaluated by multiple linear regression with a robust variance estimator. FINDINGS: Sixty-three patients were included in our study. The mean questionnaire score was 8.2±1.2 and the mean medication possession ratio value was 0.97±0.06. A total of 76% of patients were considered adherent according to the questionnaire (i.e. score ≥ 8), 94% according to the medication possession ratio (i.e. MPR ≥ 0.90), and 70% according to the questionnaire and the medication possession ratio. No statistically significant linear association was observed between the questionnaire score and any variables of interest including medication possession ratio. All Cronbach's alpha were relatively low (range 0.0342-0.2443), showing a low correlation of the different questions with the questionnaire score. CONCLUSIONS: Our study is the first prospective study evaluating IMID adherence in multiple myeloma patients in real life. The high adherence to IMIDs reported here, regardless of the drug, is encouraging considering the efficacy, toxicity and elevated cost of IMIDs. The specific questionnaire should be used with caution to evaluate IMID adherence.

What do adult outpatients included in clinical trials know about the investigational drugs being assessed: A cross-sectional study in France.

This study aimed to assess patient investigational medication knowledge and to identify factors associated with medication understanding by adult outpatients included in clinical trials. A cross-sectional prospectively designed survey was conducted on consecutive volunteers at 21 university teaching hospitals (in France) from February to December 2014. Investigational medication understanding was assessed at the time of the first dispensing using a structured interviewer-administered questionnaire based on information obtained from the literature that provided an 8-point score. Demographic and other baseline data were collected using structured interviews. Of the 236 participants, 139 (58.9%) of the respondents were male, and the median age was 54.9 years (range: 18-83 years). The mean understanding score was 6.24 and 72.5% of the patients had a score of 6 or higher. In univariate analysis, the medication understanding score was negatively correlated with age (r = -0.15, p = 0.0247) and positively correlated with the level of education (r = 0.25, p = 0.0002). In multivariate analysis, prognostic factors of a higher medication understanding score were: graduation from high school or a higher level of education; HIV infection; phase II/III/IV studies; mention of the drug on the prescription form, and the dispensing of a single investigational medication. Only a quarter of the adult outpatients included in clinical trials had a maximum possible investigational medication understanding score. Being old and having a low level of education were found to be important risk factors for inadequate medication understanding. This and other data suggest that sponsors should encourage initiatives aimed at improving investigational medication understanding in adults enrolled in clinical trials.

A single dose of tramadol in continuous wound analgesia with levobupivacaine does not reduce post-sternotomy pain: a randomized controlled trial.

BACKGROUND: Medial sternotomy is commonly used in cardiac surgery, although it results in intense post-operative pain. The placement of a sternal wound catheter for the administration of local anesthetic represents an effective technique. An initial bolus of tramadol in the sternal wound catheter could potentiate the effect of the local anesthetic and decrease both the post-operative pain and the morphine consumption. PATIENTS AND METHODS: We conducted a prospective, randomized, double-blind study at the University Hospital Center, Dijon, France. Patients requiring scheduled or non-extreme emergency surgery for valve disease, aorta disease, atrial myxoma, or coronary artery bypass graft via sternotomy were included. A sternal wound catheter was inserted at the end of the surgery. The patients were randomized to receive either a 2 mg/kg bolus of tramadol (n=80) or a placebo (n=80) in the wound catheter. The bolus administration was followed by a continuous infusion of 1.25% levobupivacaine for the first 48 hrs following surgery. The patients' morphine consumption during the first 48 hrs after extubation was recorded. The other investigated variables were the patients' rescue analgesia, arterial blood gasses, and length of stay in the intensive care unit and in hospital, as well as the incidence of chronic pain at the four-month follow-up point. RESULTS: The morphine consumption was found to be comparable in the two groups (38 mg vs 32 mg, p=0.102). No effect was found in terms of the arterial blood gasses, lengths of stay, or incidence of chronic pain. CONCLUSION: The addition of tramadol to the local anesthetic delivered via a wound catheter following sternotomy did not reduce the patients' post-operative morphine consumption. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02851394.

Trisodium citrate 4% versus heparin as a catheter lock for non-tunneled hemodialysis catheters in critically ill patients: a multicenter, randomized clinical trial.

BACKGROUND: Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent catheter dysfunction and infection with catheter locks remain controversial. METHODS: In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality. RESULTS: Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3-10) in the citrate group and 5 days (IQR 3-11) in the heparin group (p = 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups. CONCLUSIONS: In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups. Trial registration Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.