Conectar
This study assessed the feasibility of implementing a phase 3 field-based clinical trial protocol to evaluate paediatric praziquantel (PED-PZQ) for the treatment of Schistosoma mansoni infection in children aged 3 months to 6 years in endemic areas of Brazil, focusing on operational aspects such as recruitment logistics, documentation management, investigational product handling and protocol adherence.
Pilot and feasibility study for a phase 3 clinical trial, comprising two components: a randomised, open-label, parallel-group, two-arm trial and a single-arm trial.
Conde, Bahia, Brazil, from December 2024 to January 2025.
Two trials aim to screen 5774 participants from three rural areas in Bahia and three in Sergipe, states in northeastern Brazil, and enrol 403 children eligible for either randomisation or allocation. Trial 1 will randomise (1:1 ratio) 240 children aged 4–6 years into the PED-PZQ treatment arm or the standard praziquantel (PZQ) 1. Trial 2 will enrol 163 children aged 3 months to 3 years, all receiving PED-PZQ. Both trials are open label. Eligible participants shall meet age criteria, test positive for S. mansoni and fulfil other inclusion criteria. In the first recruiting centre, Conde (Bahia), it was estimated that 650 participants would need to be screened for trial 1 and 552 for trial 2, assuming schistosomiasis prevalence of 5% and 4%, respectively. This pilot study reports on the first 60 participants enrolled.
The primary outcome of this pilot study is the feasibility of implementing the research protocol in a real-world field setting, focusing on key aspects such as study documentation challenges, participant safety, investigational medicinal product custody chain and protocol adherence. In addition to providing preliminary data on the parasitological cure rate, secondary outcomes include the prevalence of S. mansoni infection and the reduction in S. mansoni egg count (Kato-Katz method). Furthermore, the occurrence and severity of drug-related adverse events are monitored from drug administration to day 21 post-treatment, alongside changes in renal, hepatic and cardiac functions assessed through biochemical markers.
A total of 60 participants were recruited, and 55 provided stool samples for screening. The pilot phase demonstrated the feasibility of implementing the clinical protocol under field conditions, with successful completion of all planned procedures and minimal protocol deviations. Operational challenges were identified mainly in documentation processes, participant recruitment and investigational product management and were addressed through preventive and corrective quality assurance actions. The experience also highlighted logistical and infrastructural barriers typical of field-based trials in remote endemic areas, which informed adjustments for the subsequent phase 3 study. Preliminary parasitological results indicated an overall S. mansoni prevalence of 9.1% (5/55), with 21% in trial 1 and 2.8% in trial 2. All infected participants met the eligibility criteria, received treatment and completed follow-up. Four achieved a parasitological cure, and one case of treatment failure was observed (trial 1, PZQ group). Two mild adverse events (diarrhoea) were reported, with no serious complications or clinically significant changes in biochemical parameters.
This pilot study demonstrated the feasibility of implementing a field-based phase 3 clinical trial protocol for PED-PZQ in endemic areas of Brazil. The findings confirm that the protocol can be successfully applied in primary care settings, despite operational challenges related to recruitment, logistics and documentation. The study also provided preliminary evidence supporting the safety and effectiveness of the paediatric formulation and highlighted the need to revise prevalence assumptions to improve future screening strategies. Overall, the experience offers valuable insights to guide the large-scale phase 3 trial and supports the incorporation of PED-PZQ into national schistosomiasis control policies.
Brazilian Clinical Trials Registry; RBR-86kcy37.
Diagnostic errors in primary care are common, particularly in the interpretation and follow-up of abnormal haemoglobin (Hgb) and estimated glomerular filtration rate (eGFR) results. These errors frequently result in missed or delayed diagnoses of serious conditions such as anaemia and chronic kidney disease. This protocol describes a stepped-wedge cluster randomised controlled trial designed to evaluate a novel, evidence-based, team-based intervention aimed at improving diagnostic safety and efficiency.
The study will be conducted across 12 University of Texas Physicians (UTPs) primary care clinics in Houston, Texas, USA. Adult patients (≥18 years) with newly identified abnormal Hgb or eGFR results will be eligible for inclusion. The intervention integrates automated tracking of abnormal laboratory results, nurse navigators to support patient follow-up and engagement, and clinical pathologists to provide diagnostic guidance to primary care providers. The primary outcome is diagnostic safety, defined as the proportion of patients who receive a correct diagnosis within 6 months. Secondary outcomes include diagnostic efficiency, appropriate test utilisation, cost-effectiveness, patient activation and implementation metrics such as acceptability, fidelity and sustainability. The study will also explore barriers and facilitators to successful implementation using mixed-methods evaluation.
This trial has been approved by the Institutional Review Board at The University of Texas Health Science Center at Houston. Study results will be disseminated through peer-reviewed publications and conference presentations, and findings will be reported to UTP leadership to inform potential system-wide implementation.
To explore prescribers’ awareness of medicine-related challenges of older people (≥65 years) with sensory impairment (hearing, visual or dual impaired) and identify the influences on prescribing behaviours for these patient populations.
Semistructured interviews were completed online.
Primary care-based prescribers in the UK.
Independent prescribers working in primary care. Participants were recruited through professional networks and organisations, social media and using snowballing. Purposive sampling was used to ensure variation in roles, practice/organisational settings and geographical location.
15 prescribers participated, including general practitioners (n=6), pharmacists (n=5), nurses (n=3) and one optometrist. Many demonstrated limited awareness of sensory impairment and suggested that outdated patient records contribute to it being easy to overlook. Prescribers underestimated sensory impairment prevalence, with one predicting that only a small proportion of older patients had hearing loss. Formal training on prescribing for older people with sensory impairment was minimal, and most relied on experiential learning. Prescribers employed strategies to support safe prescribing, such as simplifying regimens and selecting lower-risk medications. The prescribers also reported a lack of evidence-based guidelines or resources tailored to these patient populations.
Prescribers currently receive minimal training to support their prescribing practices for older people with sensory impairment. Given the increasing prevalence of age-related sensory impairment, evidence-based resources and training are needed to support prescribing for these patient populations.
Unexplained infertility affects about 30% of couples seeking help for infertility, yet the optimal ovulation induction strategy remains largely unclear. Letrozole, clomiphene citrate and gonadotropins are widely used, alone or in combination, with or without intrauterine insemination (IUI), but evidence of comparative effectiveness and safety is inconsistent. Most reviews are restricted to pairwise comparisons or mixed infertility populations. This protocol describes a systematic review and network meta-analysis (NMA) to compare ovulation induction strategies specifically in unexplained infertility.
Parallel-group randomised controlled trials (RCTs), including women aged 18–40 years with unexplained infertility, will be eligible. Interventions include letrozole, clomiphene citrate, gonadotropins, combination regimens and expectant management/ placebo, with or without IUI. The primary outcome will be live birth per woman randomised; if unavailable, ongoing or clinical pregnancy will be considered. Secondary outcomes include ovulation, multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome, ectopic pregnancy, neonatal outcomes, time to pregnancy, adverse events and cycle cancellation rates. Databases (MEDLINE/PubMed, Embase, Cochrane Library, Scopus and Web of Science), trial registry (ClinicalTrials.gov), and grey literature (postgraduate theses, conference abstracts and dissertations) will be searched from inception to September 2025. Two reviewers will independently screen, extract data and assess risk of bias (RoB-2). Pairwise random-effects meta-analyses will precede a Bayesian and frequentist NMA (if sufficient network). If feasible, component NMA will be performed to estimate marginal effects of drug and procedural components. Certainty of evidence will be assessed using the CINeMA framework (GRADE for NMA). Publication bias will be assessed using funnel plots and Egger’s test, where feasible.
No ethics approval is required. Findings will be published in peer-reviewed journals, presented at conferences and made available through open-access repositories.
CRD420251145492. The review was registered prospectively; the review start date is 11 September 2025 and the anticipated end date is 3 March 2026.
Drug poisoning, caused predominantly by fentanyl in the unregulated drug supply, is the leading cause of death among persons 10–59 years in British Columbia (BC), Canada. In March 2020, in response to the emergence of the COVID-19 pandemic, the province of BC released the Risk Mitigation Guidance (RMG) as a clinical tool for physicians and nurse practitioners, allowing prescribers to provide selective withdrawal management medications, such as hydromorphone, dextroamphetamine, diazepam and others, as a legal and regulated supply of pharmaceutical alternatives to individuals who were at-risk of COVID-19 and overdose. In July 2021, the government of BC released the prescribed safer supply (PSS) policy, extending the scope beyond the COVID-19 pandemic and initial medications offered under the RMG. Recent studies have shown clear benefits among people with a diagnosed opioid use disorder who were prescribed PSS, in reducing mortality, as well as improving retention on opioid agonist treatment for those who were coprescribed PSS medications. The objective of the analysis detailed in this protocol is to use a cross-model comparison approach, comparing two independently developed models which are currently used in public health institutions in BC, to estimate the impact of this policy on opioid overdose-related mortality, while also considering the potential negative impacts of PSS medication diversion to those who are opioid naïve. This project will add to the limited evidence-base on the population-level impact of pharmaceutical alternatives interventions to date.
We have identified two appropriate mathematical models to evaluate the impact of PSS on the number of opioid overdose-related deaths within BC from the inception of the programme (March 2020) until December 2022. We will use recently established guidelines on conducting a cross-model comparison to identify structural and parameter differences between the models and perform adaptation steps to generate the counterfactual scenarios. These will include creating additional health states for the population representing individuals receiving PSS, and parameterising the overdose risk, mortality and retention in the new compartments from a comprehensive population-level data set. Harmonisation will be conducted to ensure that both models evaluate the same scenarios with the same data. Further sensitivity analyses will be conducted to consider alternative counterfactual scenarios and changes to the population following the implementation of the intervention.
This study is exempt from research ethics board review, as outlined in the Tri-Council Policy Statement, because it relies on data that is available in the public domain and there is no possibility of identifying individual persons. Results of the model validation analysis will be distributed through peer-reviewed journals and knowledge translation materials posted on the websites of the BC Centre for Disease Control and Centre for Advancing Health Outcomes.
Streptococcus pneumoniae serotype 3 (SPN3) remains a significant contributor to invasive pneumococcal disease globally, despite its inclusion in widely administered vaccines. The next generation of pneumococcal vaccines may confer better protection against this serotype, reducing disease burden. We describe an ethically approved protocol for a double-blind randomised controlled trial assessing the impact of VAXNEUVANCE (15-valent pneumococcal conjugated vaccine (PCV15)) and 0.9% saline (placebo) on the acquisition, density and duration of SPN3 carriage using a controlled human infection model.
Healthy adults aged 18–50 years will be randomised 1:1 to receive PCV15 or placebo. Participants will be considered enrolled on the trial at vaccination. One month following vaccination, all participants will be intranasally inoculated with SPN3. Following inoculation, participants will be followed up on days 2, 7, 14 and 28 to monitor safety, SPN3 colonisation status, density and duration, as well as immune responses. The primary endpoint of the study is to assess the rate of SPN3 acquisition between vaccinated and unvaccinated participants defined by classical microbiological methods. Secondary endpoints will determine the density and duration of SPN3 colonisation and compare the immune responses between study groups. An exploratory cohort of 5 participants will be asked to consent to a nasal biopsy procedure during a screening visit and a second nasal biopsy 28 days after PCV15 vaccination. This cohort will only receive PCV15 and will not be challenged. Through this exploratory cohort, we will explore gene expression changes induced by PCV15 vaccination and their visualisation (spatial location) within the nasal tissue.
This protocol has been reviewed by the sponsor, funder and external peer reviewers. The study is approved by the NHS Research and Ethics Committee (Reference: 24/SC/0388) and by the Medicines and Healthcare Products Regulatory Agency (Reference: CTA 21584/0485/001-0001).
The introduction of fentanyl and its analogues in the illicit drug supply has prompted greater emphasis on refining clinical treatment protocols to ensure sustained retention in opioid agonist treatment (OAT). Take-home dosing may lessen the treatment burden on clients and thus reduce the risk of treatment discontinuation. The evidence base supporting the use of take-home dosing, including the optimal duration of dispensations, is, however, limited. The objective of this study is to determine the comparative effectiveness of alternative take-home dosing schedules, as observed in clinical practice in British Columbia, Canada from 2010 to 2022.
We propose to emulate a target trial with a population-level retrospective study of individuals initiating methadone or buprenorphine/naloxone between 1 January 2010 and 31 December 2022 who are 18 years of age or older and not currently incarcerated or pregnant with no history of cancer or palliative care. Our study will draw on nine linked health administrative databases from British Columbia and will evaluate take-home doses of 2–5 days, 6 days or >6 days compared with continuous daily dosing. The primary outcomes include OAT discontinuation and all-cause mortality on treatment. A causal per-protocol analysis is proposed with longitudinal matching and inverse probability of censoring weighting approaches to adjust for time-fixed and time-varying confounding. A range of sensitivity analyses will be executed to determine the robustness of results.
The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated and shared with local advocacy groups and decision-makers, developers of national and international clinical guidelines, presented at national and international conferences and published in peer-reviewed journals electronically and in print.
There is an absence of real-world evidence, especially from low- and middle-income countries (LMICs), on the implementation successes and challenges of COVID-19 Test and Treat (T&T) programmes. In 2022, nirmatrelvir/ritonavir was provided as standard of care for mild to moderate COVID-19 treatment in eight LMICs (Ghana, Kenya, Laos, Malawi, Nigeria, Rwanda, Uganda and Zambia). This manuscript describes a research protocol to study novel drug introduction during the COVID-19 health emergency, with implications and learnings for future pandemic preparedness. The goal of the study is to provide simultaneous programme learnings and improvements with programme rollout, to fill a gap in real-world implementation data on T&T programmes of oral antiviral treatment for COVID-19 and inform programme implementation and scale-up in other LMICs.
This multiple methods implementation research study is divided into three components to address key operational research objectives: (1) programme learnings, monitoring and evaluation; (2) patient-level programme impact; and (3) key stakeholder perspectives. Data collection will occur for a minimum of 6 months in each country up to the end of grant. Quantitative data will be analysed using descriptive statistics for each country and then aggregated across the programme countries. Stakeholder perspectives will be examined using the Consolidated Framework for Implementation Research implementation science framework and semistructured interviews.
This study was approved by the Duke University Institutional Review Board (Pro00111388). The study was also approved by the local institutional review boards in each country participating in individual-level data collection (objectives 2 and 3): Ghana, Malawi, Rwanda, Nigeria and Zambia. The study’s findings will be published in peer-reviewed journals and disseminated through dialogue events, national and international conferences and through social media.
Malawi’s prisons are overcrowded, contributing to tuberculosis (TB) and Human Immunodeficiency Virus (HIV) transmission and service delivery gaps for both conditions. We applied an empirically supported three-stage model of HIV/TB care to guide the improvement of TB/HIV service delivery in select Malawian prisons.
We conducted a pilot implementation research study using multimethods from May 2022 to April 2023.
Two semi-urban prisons in Malawi.
We purposively sampled participants detained at the study sites during the study period.
We collected data on sociodemographics, medical history and screening results for sexually transmitted infections (STIs), HIV and TB results. We conducted in-depth interviews with prison professional staff and used content analysis to explore the feasibility of implementing the three-stage model of HIV and TB care in Malawian prisons.
Mean participant age was 35 years (SD 12.2 years). We screened 100 out of 647 (15%) incarcerated people for TB/HIV according to the three-stage model and identified the following: five cases of TB disease; two cases of HIV-associated TB; seven persons living with HIV; eight persons diagnosed and treated for STIs, including genital ulcer disease and syphilis. For those tested for HIV at entry, midpoint and exit screening, there was no documented case of seroconversion during the incarceration period. There was evidence of potential STI transmission during incarceration, as suggested by a 4% rate of new urethral discharge among participants. Qualitative data suggest that it is feasible to implement the three-stage model of HIV/TB in the Malawi prison setting.
We found evidence of HIV, TB and STIs among incarcerated people in two semi-urban prisons in Malawi, with low HIV status awareness on prison entry. It is feasible to implement the three-stage model of HIV/TB in prison settings, although with material support to overcome implementation challenges. Coordination with Ministry of Health officials could facilitate model feasibility and sustainability in Malawi’s prisons.
Little research has been done on post-COVID symptoms at 24 months postinfection and on the association these may have on health-related quality of life (HRQOL).
We assessed the prevalence and severity of post-COVID symptoms and quantified EuroQol 5 Dimension 5 Level (EQ-5D-5L), self-perceived health question (EuroQol Visual Analogue Scale (EQ-VAS)) and health utility scores (HUS) up to 24 months follow-up.
The longitudinal multiple cohort CORona Follow-Up (CORFU) study combines seven COVID-19 patient cohorts and a survey among the general public. The participants received questionnaires on several time points. Participants were stratified by: without a known SARS-CoV-2 infection (control group), proven SARS-CoV-2 infection but non-hospitalised, proven SARS-CoV-2 infection hospitalised to the ward, and proven SARS-CoV-2 infection hospitalised to the intensive care unit (ICU).
In this study, data of seven COVID-19 patient cohorts and a survey among the general public are included.
Former COVID-19 patients and controls participated in this cohort study.
Former COVID-19 patients and non-COVID-19 controls were sent questionnaires on symptoms associated with post-COVID condition. The CORFU questionnaire included 14 symptom questions on post-COVID condition using a five-level Likert-scale format. Furthermore, HRQOL was quantified using the EuroQol EQ-5D-5L questionnaire: EQ-VAS and the EQ-5D-5L utility score. The EQ-5D-5L questionnaire includes five domains that are scored on a five-point Likert scale: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.
A total of 901 participants (and 434 controls) responded at 24 months follow-up. In all former COVID-19 patients, the presence of post-COVID condition at 24 months was observed in 62 (42.5%, 95% CI 34.3% to 50.9%) of the non-hospitalised patients, 333 (65.0%, 95% CI 60.7% to 69.2%) of the hospitalised ward patients and 156 (63.2%, 95% CI 56.8% to 69.2%) of the ICU patients, respectively (p
Many former COVID-19 patients experience post-COVID symptoms at 24 months follow-up, with the highest prevalence in hospitalised participants. Also, former patients reported a lower HRQOL.
The CORFU study was registered at clinicaltrials.gov (registration number NCT05240742).
Acute pain in the postoperative period of cardiac surgery is mostly treated with opioid analgesics. However, with the risk of adverse reactions and complications, strategies which do not involve opioid analgesics can be considered, such as aromatherapy. This systematic review aims to analyse the effectiveness of aromatherapy in relieving pain in post-cardiac surgery patients.
Two researchers will independently and simultaneously conduct searches and select studies from the following databases: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Literature on Health Sciences, Scopus, Web of Science, Cochrane (Library) and clinical trial registries (clinicaltrials.com), with no language or publication date restrictions. Randomised and quasi-randomised clinical trials on the use of aromatherapy for pain relief in postcardiac surgery patients will be included. Then, two researchers will independently examine the studies based on inclusion criteria, extract data from the included studies and assess the risk of bias using the Risk of Bias 2 tool and the Risk of Bias in Non-randomized Studies of Interventions tool from Cochrane. Data will be synthesised using Review Manager software. The strength of the evidence will be evaluated using the Grading of Recommendation Assessment, Development and Evaluation approach. The literature search, study selection, review and meta-analysis stages will be conducted from early October 2025 to April 2026.
This study is based on secondary data, and therefore ethical approval from a research ethics committee was not required. The results will be disseminated through publication in a peer-reviewed scientific journal.
CRD42024568532.
Alcohol dependence (AD) is highly prevalent and has severe consequences on health and quality of life. However, the efficacy of approved pharmacotherapies such as naltrexone (NTX) remains limited, highlighting the need for novel pharmacotherapeutic approaches. Cannabidiol (CBD) is a promising candidate, which has shown potential to reduce craving and alcohol use by modulating brain circuits involved in craving and addiction. Preclinical studies suggest that CBD may enhance NTX’s therapeutic effects.
This is a three-armed, randomised, double-blind, placebo-controlled parallel group, multicentre phase II clinical trial. A total of 150 patients with AD will be randomised (1:1:1) to receive either 800 mg or 1200 mg CBD plus 50 mg oral NTX or placebo plus 50 mg oral NTX for 14 days. Alcohol craving will be assessed using the Obsessive Compulsive Drinking Scale (OCDS-G) where the primary endpoint is the change from baseline to the end of treatment. Secondary outcomes include craving during the entire study, quality of life, depressive symptoms, anxiety, patient-reported outcomes, neural brain activation, CBD plasma levels, time to relapse, alcohol use and treatment safety. For the comparison of each experimental group to the control group, a strata-adjusted (centre and baseline OCDS-G) van Elteren test is applied with adjustment for multiple testing by Bonferroni-Holm.
The trial has been approved by the Ethics Committee and the competent authority (ID: B_03510). All participants will provide written informed consent. An independent Data and Safety Monitoring Board will monitor safety. This trial complies with national and international regulations.
NCT06845124; EU Trial Number: 2024-518164-12-00.
Opioid use disorder (OUD) during pregnancy is associated with increased rates of adverse perinatal, foetal and neonatal health events. Opioid agonist treatment (OAT) can substantially reduce the risk of these potential harms. In British Columbia (BC), methadone and buprenorphine/naloxone are first-line treatment options for pregnant people with OUD. However, the comparative effectiveness of these regimens during pregnancy remains poorly understood, particularly in terms of how dosage may impact clinical outcomes. This protocol outlines a proposed population-based retrospective study to evaluate the comparative effectiveness of methadone compared with buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes.
We propose to conduct a retrospective observational study using population-based data from individuals who received methadone or buprenorphine/naloxone during pregnancy between 1 April 2010 and 31 March 2022. Data will be collected from 10 linked population-level administrative databases. We will emulate target trials using intention-to-treat and per-protocol approaches. We will use a pooled logistic regression approach to assess the impact of methadone versus buprenorphine/naloxone on time to OAT episode discontinuation and a dose-response marginal structural model to evaluate neonatal health at delivery. An exploratory observational analysis will also be conducted to describe the impact of methadone vs buprenorphine exposure during the first trimester of pregnancy on congenital malformations and anomalies.
This study has been determined to meet the criteria for exemption per Article 2.5 of the 2018 Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. Study databases have been made available by the BC Ministries of Health and Mental Health and Addiction as part of the provincial opioid overdose public health emergency response. Results will be disseminated to policymakers, clinical partners, community programmes and people with lived and living experience of substance use and published in peer-reviewed journals.
Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disease characterised by cognitive, behavioural and motor problems. Motor symptoms are highly disabling, while cognitive and behavioural changes have a major impact on carer burden, quality of life and prognosis. Apathy and impulsivity are very common, often coexistent in PSP, and negatively predict survival. In preclinical models and other diseases, apathy and impulsivity are associated with noradrenergic deficits, which can be severe in PSP.
Noradrenaline for Progressive Supranuclear Palsy Syndromes trial is a randomised, double-blind, placebo-controlled, crossover design, Phase IIb clinical trial to evaluate the efficacy and safety of oral atomoxetine for the treatment of cognitive and behavioural changes in PSP. Participants receive atomoxetine 40 mg (10 mg/mL oral solution) once daily or a matched placebo solution, in random order, each for 8 weeks. An ‘informant’, who knows the patient with PSP well, is co-recruited to complete some of the trial outcome measures. Participants remain in the trial for 22 weeks after randomisation. The primary objectives are to assess (1) safety and tolerability and (2) efficacy versus placebo on challenging behaviours as reported in a subscale of the Cambridge Behavioural Inventory. Secondary and exploratory measures relate to cognition, the PSP Rating Scale, mood and potential baseline predictors of individual response to atomoxetine computed from imaging, genetic and cognitive measures at baseline.
The trial was approved by the South Central-Oxford B Research Ethics Committee (REC) and the Medicines and Healthcare products Regulatory Agency (REC reference: 20/SC/0416). Dissemination will include publication in peer-reviewed journals, presentations at academic and public conferences and engagement with patients, the public, policymakers and practitioners.
ISRCTN99462035; DOI:
FreshRSS 