Belgian Health Care Knowledge Centre Research Articles

Effect of high versus standard protein provision on functional recovery in people with critical illness (PRECISe): an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in Belgium and the Netherlands

Increased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2·0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1·3 g/kg per day). The PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m2, kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1·3 kcal/mL and 0·06 g of protein/mL (ie, standard protein) or 1·3 kcal/mL and 0·10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants. Between Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35·8%) of 935 patients were female and 600 (64·2%) were male. 465 (49·7%) of 935 were assigned to the standard protein group and 470 (50·3%) were assigned to the high protein group. 430 (92·5%) of 465 patients in the standard protein group and 419 (89·1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of -0·05 (95% CI -0·10 to -0·01; p=0·031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0·38 (SE 0·02) in the standard protein group and 0·42 (0·02) in the high protein group (hazard ratio 1·14, 95% CI 0·92 to 1·40; p=0·22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1·76, 95% CI 1·06 to 2·92; p=0·030). Incidence of other adverse events did not differ between groups. High enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission. Netherlands Organisation for Healthcare Research and Development and Belgian Health Care Knowledge Centre.

Effect of screening for Neisseria gonorrhoeae and Chlamydia trachomatis on incidence of these infections in men who have sex with men and transgender women taking HIV pre-exposure prophylaxis (the Gonoscreen study): results from a randomised, multicentre, controlled trial

Guidelines recommend screening for Neisseria gonorrhoeae and Chlamydia trachomatis at three anatomical sites (urethra, anus, and pharynx) every 3 months (3 × 3) in men who have sex with men (MSM) and transgender women taking HIV pre-exposure prophylaxis (PrEP). We present the first randomised controlled trial to compare the effect of screening versus non-screening for N gonorrhoeae and C trachomatis on the incidence of these infections in MSM and transgender women taking PrEP. A multicentre, randomised, controlled trial of 3 × 3 screening for N gonorrhoeae and C trachomatis versus non-screening was done among MSM and transgender women taking PrEP in five HIV reference centers in Belgium. Participants attended the PrEP clinics quarterly for 12 months. N gonorrhoeae and C trachomatis was tested at each visit in both arms, but results were not provided to the non-screening arm, if asymptomatic. The primary outcome was incidence rate of N gonorrhoeae and C trachomatis infections in each arm, assessed in the per-protocol population. Non-inferiority of the non-screening arm was proven if the upper limit of the 95% CI of the incidence rate ratio (IRR) was lower than 1·25. This trial is registered with ClinicalTrials.gov, NCT04269434, and is completed. Between Sept 21, 2020, and June 4, 2021, 506 participants were randomly assigned to the 3 × 3 screening arm and 508 to the non-screening arm. The overall incidence rate of N gonorrhoeae and C trachomatis was 0·155 cases per 100 person-days (95% CI 0·128-0·186) in the 3 × 3 screening arm and 0·205 (95% CI 0·171-0·246) in the non-screening arm. The incidence rate was significantly higher in the non-screening arm (IRR 1·318, 95% CI 1·068-1·627). Participants in the non-screening arm had a higher incidence of C trachomatis infections and symptomatic C trachomatis infections. There were no significant differences in N gonorrhoeae infections. Participants in the non-screening arm consumed significantly fewer antimicrobial drugs. No serious adverse events were reported. We failed to show that non-screening for N gonorrhoeae and C trachomatis is non-inferior to 3 × 3 screening in MSM and transgender women taking PrEP in Belgium. However, screening was associated with higher antibiotic consumption and had no effect on the incidence of N gonorrhoeae. Further research is needed to assess the benefits and harms of N gonorrhoeae and C trachomatis screening in this population. Belgian Health Care Knowledge Centre.

Lumbalgie als symptoom van een extramedullaire tumor bij acute myeloïde leukemie

Lumbago as a symptom of an extramedullary tumour in acute myeloid leukaemia A 58-year-old man with acute myeloid leukaemia presents with low back pain. Because of his oncologic history and severe pain during the night, additional radiographic imaging was performed. These alarm signals or so-called red flags are described in the guidelines of the Belgian Health Care Knowledge Centre (KCE). Imaging showed a mass at the 10th thoracic vertebra, suspected to be an extramedullary tumour consisting of myeloblasts, originating from the previously diagnosed acute myeloid leukaemia. A biopsy confirmed this diagnosis. Since these tumours present with different symptoms and at different locations, every physician should be aware of them. They are treated systemically with chemotherapy, like the intramedullary disease, sometimes supplemented with local therapy. In some cases, this disease manifestation presents prior to or without the diagnosis of acute myeloid leukaemia. A correct histological diagnosis is then essential for a correct treatment.

Improving the visibility of the institution, researchers, and publications by introducing specific identifiers (PIDs)

In the course of 2021, the Belgian Health Care Knowledge Centre (KCE) has decided to give further thought to improving the visibility of these publications. This has led it to develop a project to set up three types of PIDs - one for the institution, another for researchers and the third for the publications themselves. The purpose of this text is to retrace the various stages in the project's implementation and to share the initial findings.

A randomized controlled trial comparing conservative versus surgical treatment in patients with foot drop due to peroneal nerve entrapment: results of an internal feasibility pilot study

BackgroundBased on the lack of literature to support any treatment strategy in patients with foot drop due to peroneal nerve entrapment, a prospective study randomizing patients between surgery and conservative treatment is warranted. Since studies comparing surgery to no surgery are often challenging, we first examined the feasibility of such a randomized controlled trial.Methods/designAn internal feasibility pilot study was conducted to assess several aspects of process, resource, management, and scientific feasibility. The main objective was the assessment of the recruitment rate. The criterion to embark on a full study was the recruitment of at least 14 patients in 6 participating centers within 6 months. Cross-over rate, blinding measures, training strategies, and trial assessments were evaluated. The trial was entirely funded by the KCE Trials public funding program of the Belgian Health Care Knowledge Centre (ID KCE19-1232).ResultsThe initial duration was prolonged due to the COVID-19 pandemic. Between April 2021 and October 2022, we included 19 patients of which 15 were randomized. Fourteen patients were treated as randomized. One drop-out occurred after randomization, prior to surgery. We did not document any cross-over or accidental unblinding. Training strategies were successful. Patients perceived the quality of life questionnaire as the least relevant assessment. Assessment of ankle dorsiflexion range of motion was prone to interobserver variability. All other trial assessments were adequate.DiscussionRecruitment of the anticipated 14 patients was feasible although slower than expected. The Short-Form Health Survey (SF-36) and assessment of ankle dorsiflexion range of motion will no longer be included in the full-scale FOOTDROP trial.ConclusionThe FOOTDROP study is feasible.Trial registrationClinicalTrials.gov, identifier NCT04695834. Registered 4 January 2021.

Convalescent Plasma for Covid-19–Induced ARDS in Mechanically Ventilated Patients

BackgroundPassive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19–induced acute respiratory distress syndrome (ARDS).MethodsIn this open-label trial, we randomly assigned adult patients with Covid-19–induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28.ResultsA total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P=0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups.ConclusionsThe administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19–induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.)

Access to health care for people with intellectual disability in Belgium: challenges and solutions

Abstract Background people with intellectual disability (PWID), such as those living with Down syndrome, experience poorer health outcomes, are more at-risk of comorbidities and have a lower life expectancy than the general population. Moreover, they are more likely to experience discrimination and refusal of care than other citizens. To support the implementation of the rights of PWID as promoted by the United Nations Convention on the Rights of Persons with Disabilities, the Belgian Health Care Knowledge Centre measured the health disparities between PWID and without ID in Belgium, collected the barriers faced by PWID and suggested solutions. Methods a mixed method study was conducted in 2020-2022. Quantitative data were obtained from linking the social security data related to PWID to the health expenditures data. A representative population sample was obtained to allow for compare PWID with the general population. Experiences and needs of PWID and of professionals were collected through semi-directive interviews and nominal groups. Stakeholders from handicap and health sectors joined an online survey to gather possible options for solutions. Results data of 17 155 PWID were analysed and compared to a sample of the Belgian population. PWID have, i.e., a lower access to dental care (49.8% for PWID vs 65.8% in 2019) or breast cancer screening (42.6% for PWID vs 59.7%). We found no difference for contact with a GP and diabetes follow-up. Five categories of barriers emerged: stereotypes and prejudices; lack of knowledge and competences; poor communication; organisational gaps; lack of sociopolitical support. We identified 25 actions, aiming at 8 objectives, with 3 preliminary conditions: more time, universal design and reasonable adjustment. Conclusions focusing on universal design, that is tailoring health services to the needs of the most vulnerable patients that are PWID, can increase access to health care to all patients and not only the PWID. Key messages • People with intellectual disability lack of access to preventive health care. • Focusing on universal design increases access to health care for all.

Managing uncertainty in forecasting health workforce demand using the Robust Workforce Planning Framework: the example of midwives in Belgium

BackgroundIn Belgium, the Planning Commission for Medical Supply is responsible for monitoring human resources for health (HRH) and ultimately proposing workforce quotas. It is supported by the Planning Unit for the Supply of the Health Professions. This Unit quantifies and forecasts the workforce in the healthcare professions on the basis of a stock and flow model, based on trends observed in the past. In 2019, the Planning Unit asked the KCE (Belgian Health Care Knowledge Centre) to develop additional forecasting scenarios for the midwifery workforce, to complement the standard historical trend approach. The aim of this paper is to present the development of such forecasting scenarios.MethodsThe Robust Workforce Planning Framework, developed by the Centre for Workforce Intelligence in the UK was used to develop alternative midwifery workforce scenarios. The framework consists of four steps (Horizon scanning, Scenario generation, Workforce modelling, and Policy analysis), the first two of which were undertaken by KCE, using two online surveys and five workshops with stakeholders.ResultsThree alternative scenarios are proposed. The first scenario (close to the current situation) envisages pregnancy and maternity care centred on gynaecologists working either in a hospital or in private practice. The second scenario describes an organisation of midwife-led care in hospitals. In the third scenario, care is primarily organised by primary care practitioners (midwives and general practitioners) in outpatient settings.ConclusionsThe Robust Workforce Planning Framework provides an opportunity to adjust the modelling of the health workforce and inform decision-makers about the impact of their future decisions on the health workforce.

R WE ready for reimbursement? A round up of developments in real-world evidence relating to health technology assessment: part 12.

In this latest update we highlight the final results from the RCT-DUPLICATE initiative, the publication of guidance from Haute Autorité de Santé (HAS), the joint viewpoint from the Institute for Quality and Efficiency in HealthCare (IQWIG) and the Belgian HealthCare Knowledge Center, and a position from the European Organization for Research and Treatment of Cancer (EORTC). Finally, we discuss how the NICE RWE framework has been implemented to allow consideration of RWE external control arms.

Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus

BackgroundCyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain.MethodsIn this multicenter, noninferiority trial, we randomly assigned infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<28 weeks’ gestational age) to receive either expectant management or early ibuprofen treatment. The composite primary outcome included necrotizing enterocolitis (Bell’s stage IIa or higher), moderate to severe bronchopulmonary dysplasia, or death at 36 weeks’ postmenstrual age. The noninferiority of expectant management as compared with early ibuprofen treatment was defined as an absolute risk difference with an upper boundary of the one-sided 95% confidence interval of less than 10 percentage points.ResultsA total of 273 infants underwent randomization. The median gestational age was 26 weeks, and the median birth weight was 845 g. A primary-outcome event occurred in 63 of 136 infants (46.3%) in the expectant-management group and in 87 of 137 (63.5%) in the early-ibuprofen group (absolute risk difference, −17.2 percentage points; upper boundary of the one-sided 95% confidence interval [CI], −7.4; P<0.001 for noninferiority). Necrotizing enterocolitis occurred in 24 of 136 infants (17.6%) in the expectant-management group and in 21 of 137 (15.3%) in the early-ibuprofen group (absolute risk difference, 2.3 percentage points; two-sided 95% CI, −6.5 to 11.1); bronchopulmonary dysplasia occurred in 39 of 117 infants (33.3%) and in 57 of 112 (50.9%), respectively (absolute risk difference, −17.6 percentage points; two-sided 95% CI, −30.2 to −5.0). Death occurred in 19 of 136 infants (14.0%) and in 25 of 137 (18.2%), respectively (absolute risk difference, −4.3 percentage points; two-sided 95% CI, −13.0 to 4.4). Rates of other adverse outcomes were similar in the two groups.ConclusionsExpectant management for PDA in extremely premature infants was noninferior to early ibuprofen treatment with respect to necrotizing enterocolitis, bronchopulmonary dysplasia, or death at 36 weeks’ postmenstrual age. (Funded by the Netherlands Organization for Health Research and Development and the Belgian Health Care Knowledge Center; BeNeDuctus ClinicalTrials.gov number, NCT02884219; EudraCT number, 2017-001376-28.)

Understanding how organisational culture supports patient involvement in a national research agency

Abstract Background The Belgian Health Care Knowledge Centre (KCE) formally involves stakeholders in its researches since 2012. Patients are treated as one stakeholder amongst others, but it is recognized that patient involvement (PI) requires a different approach. The success of implementing PI depends, however, on the organizational culture towards PI. Objectives The objective of this study was to map the PI culture at KCE in the context of the development of organization-wide supported position statements about PI. Methods A nominal group technique was used to measure the PI culture at KCE. Arguments for and against PI and conditions for PI in different phases of the research process were collected. A literature review and interviews fed the draft position statements, for which support was assessed by means of a two-round Delphi process. Results Arguments in favour of PI in research related to the relevance of the scope, expertise with data collection, bringing in fresh ideas for study design, access to survey participants, validation of data analyses, adherence to recommendations. Disadvantages and risks included the lack of scientific knowledge of involved patients, resources requirements, conflicts of interest, and heterogeneity within patient populations. Conditions for meaningful PI referred to measures mitigating the identified disadvantages. Eighteen position statements supported by KCE could be formulated. Conclusions The KCE culture seems predominantly positive towards PI, although attitudes vary between researchers. KCE recognizes the potential value of PI in research, but considers the level of involvement to be contingent on the topic and phase in the research process. Key messages • Organizational culture towards patient involvement is a driver of successful researches. • 18 position statements supported implementation of patient involvement in a national health agency.

Supporting patient involvement in health service research: development of a methodological guidance

Abstract Background The Belgian Health Care Knowledge Centre (KCE) issued a Position Paper in 2019 regarding the Patient Involvement (PI) in its researches as stakeholders. After previously investigating the organizational culture of the KCE, a key element for a successful implementation of PI was providing methodological guidance to the researchers. Objectives The objective of this study was to develop a methodological guidance for implementing PI into the practices of researchers at KCE. Methods In order to build a practical and effective process note, reflecting the needs and points of attention of all involved participants, different methods were combined: a literature review, workshops with the umbrellas of patient associations, patients and patient representatives, Delphi survey and a pilot project involving patients as research partners. Results The resulting guidance identified 5 prerequisites and conditions for implementation of patient involvement at the organisational level. The guidance also focused on how to involve patients (which patients, how, when, what for) and included general recommendations to researchers during the collaboration (communication, relational aspects, animation techniques, specific needs of patients). Recommendations for the reporting and evaluation of PI were also formulated. Alongside the guidance for researchers, supports for patients were also developed and validated by the patient associations. Conclusions The KCE guidance for PI in research could inspire other agencies willing to implement PI in their practices. Implementation will therefore require additional human and financial resources. Key messages

Perspectives of long COVID patients on their (unmet) needs: a national quantitative and qualitative study

Abstract Introduction After COVID-19, many people continue to experience various symptoms for several weeks, even after a mild acute phase, and encounter difficulties when confronted with the healthcare system. Patient associations asked the Belgian Health Care Knowledge Centre to investigate the needs of these patients to improve their management. Purpose of research An online quantitative survey was conducted in 2021 among Belgian patients with history of COVID-19; having/had persisting symptoms for at least 4 weeks. Alongside questions on symptoms, treatment and impact on employment, Health-Related Quality of Life (HRQoL) before and after COVID-19 was measured through the EQ-5D-5L. A regression analysis identified the factors associated with the impact of long COVID on HRQoL. The qualitative approach consisted in 33 interviews and forum discussions among 101 patients. Results 1320 patients completed the online survey, most were symptomatic for more than 3 months. The average EQ-5D-5L index score was 0.85(95%CI:0.83-0.86) before and 0.65(95%CI:0.63-0.66) after infection. Duration, number and type of symptoms of long COVID significantly impacted HRQoL. More than half of the patients were unable to work. Qualitative part identified lack of empathy of health professionals, of systematic diagnostic approach, of interdisciplinary coordination. Patients felt misunderstood and developed their own diagnostic or treatment strategies. They questioned the value of medicine and resorted to non-reimbursed alternative therapies. Conclusions Long COVID has a significant impact on HRQoL and employment. Because of long COVID, patients were confronted, sometimes for the first time, with the imperfections of the health system. Better informing the health professionals on Long COVID patterns and management options, including reimbursement possibilities, and a comprehensive interdisciplinary assessment would give them the tools to respond to the needs of these patients.

Acetazolamide in Acute Decompensated Heart Failure with Volume Overload

BackgroundWhether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear.MethodsIn this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro–B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed.ResultsA total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups.ConclusionsThe addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.)

In IBS, a smartphone application for self-managing a FODMAP-lowering diet vs. otilonium bromide reduced symptoms at 8 wk.

Carbone F, Van den Houte K, Besard L, et al. Diet or medication in primary care patients with IBS: the DOMINO study-a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute. Gut. 2022. [Epub ahead of print]. 35483886.

Diet or medication in primary care patients with IBS: the DOMINO study - a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute

BackgroundIn Europe, IBS is commonly treated with musculotropic spasmolytics (eg, otilonium bromide, OB). In tertiary care, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet provides significant improvement. Yet,...

Langdurige Covid: de contouren worden langzaam duidelijk

Long Covid: what is already known about this new condition? Long COVID affects people who have experienced a severe form of COVID-19, as well as patients who suffered a mild form. Six months after infection with the coronavirus, at least 1 out of 7 patients still have symptoms. These symptoms are very diverse and are probably related to a combination of different mechanisms: direct organ damage due to the viral infection, abnormal immune and inflammatory responses that can lead to dysfunctions on several levels (microcirculation, coagulation, fibrosis, autoimmunity, metabolism), consequences of the hospitalisation (muscle atrophy, post-intensive care syndrome) or worsening of existing comorbidities. The Belgian Healthcare Knowledge Centre (KCE) surveyed the experience of Belgian patients by means of an extensive online survey of 1,320 people, followed by an online forum and in-depth interviews. It showed that the perception of the symptoms was very diverse, with a clear reduction in the quality of life, some loss of autonomy and difficulties when returning to work. The psychological consequences could be severe. Based on the current state of science, it is not known which treatments are effective for long COVID. A symptom-oriented approach, focused on gradual multidisciplinary rehabilitation, seems appropriate. Therefore, the main recommendation of the KCE is to investigate the possibility of introducing an ‘interdisciplinary bilan’ for patients with different and interrelated complaints.

OP248 A Minimum Data-Set For Left Ventricular Assist Device On Destination Therapy: Cross-Border Collaboration Pilot On Real World Data

IntroductionThe European Health Technology Assessment Network (EUnetHTA) Work Package 5B1, is focused on testing the levels of cross-border collaboration on real world data for supporting reimbursement/pricing decision-making. Within this Work Package, we are conducting a pilot on Left Ventricular Assist Device on destination therapy in collaboration with the National Institute for Health and Care Excellence (NICE, UK), the Belgian Health Care Knowledge Centre (KCE, Belgium) and the Italian National Agency for Regional Health Services (AGENAS, Italy). This pilot aims to define the minimum data set for gathering and sharing high quality registry data on key uncertainties found at the time of the health technology assessment (HTA). Furthermore, the pilot will assess the feasibility of carrying out a common analysis or reusing this data for National or Joint Reassessments.MethodsEvidence gaps were based on the four national assessments. Collaborating partners were responsible for agreeing on the key outcomes and proposing the minimum dataset to be registered. European clinical experts and patients rated and prioritized the dataset using a two round Delphi technique (not relevant, important but not critical; critical). The dataset will confirm the basis for the Spanish LVAD registry, implemented at the national health service level to inform inclusion into the healthcare portfolio.ResultsThe key outcomes agreed upon by agencies relate to safety, effectiveness, satisfaction and acceptability of the patient and cost-effectiveness, budget impact and organizational impact. Expert cardiologists and cardiac surgeons representing the European and Spanish Society, among others, participated in the prioritization of basic data. The final dataset is expected by December 2020.ConclusionsThe variation in the quality and definition of outcome measures for measuring key evidence gaps reduces the utility of registries for HTA, making it difficult to compare, link, and aggregate data across countries. The EUnetHTA pilot is intended to offer a model for cross-border collaboration on real world data for supporting the decision-making process for pricing and reimbursement.

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

BackgroundThe antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support.MethodsDisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948.FindingsBetween March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77–1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome).InterpretationNo clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support.FundingEuropean Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation.TranslationFor the French translation of the abstract see Supplementary Materials section.

Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial