-
JMIR Research Protocols Oct 2023Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids given to hospitalized patients. Despite concern about possible harm associated with NS (eg,...
A Hospital-Wide Open-Label Cluster Crossover Pragmatic Comparative Effectiveness Randomized Trial Comparing Normal Saline to Ringer's Lactate: Protocol and Statistical Analysis Plan of The FLUID Trial.
BACKGROUND
Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids given to hospitalized patients. Despite concern about possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function, and death), few large multicenter randomized trials focused on critically ill patients have compared these fluids. Uncertainty exists about the effects of these fluids on clinically important outcomes across all hospitalized patients.
OBJECTIVE
The FLUID trial is a pragmatic, multicenter, 2×2 cluster crossover comparative effectiveness randomized trial that aims to evaluate the effectiveness of a hospital-wide policy that stocks either NS or RL as the main crystalloid fluid in 16 hospitals across Ontario, Canada.
METHODS
All hospitalized adult and pediatric patients (anticipated sample size 144,000 patients) with an incident admission to the hospital over the course of each study period will be included. Either NS or RL will be preferentially stocked throughout the hospital for 12 weeks before crossing to the alternate fluid for the subsequent 12 weeks. The primary outcome is a composite of death and hospital readmission within 90 days of hospitalization. Secondary outcomes include death, hospital readmission, dialysis, reoperation, postoperative reintubation, length of hospital stay, emergency department visits, and discharge to a facility other than home. All outcomes will be obtained from health administrative data, eliminating the need for individual case reports. The primary analysis will use cluster-level summaries to estimate cluster-average treatment effects.
RESULTS
The statistical analysis plan has been prepared "a priori" in advance of receipt of the trial data set from ICES and any analyses.
CONCLUSIONS
We describe the protocol and statistical analysis plan for the evaluation of primary and secondary outcomes for the FLUID trial.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04512950; https://classic.clinicaltrials.gov/ct2/show/NCT04512950.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/51783.
PubMed: 37801356
DOI: 10.2196/51783 -
Trials Dec 2023Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization-frozen embryo transfer (IVF-FET) among...
Effect of transvaginal Lactobacillus supplementation on reversing lower genital tract dysbiosis and improving perinatal outcomes in PCOS patients after IVF-FET: a study protocol for a multicenter randomized controlled trial.
BACKGROUND
Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization-frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET.
METHODS/DESIGN
This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography-mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited.
DISCUSSION
This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET.
ETHICS AND DISSEMINATION
Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed.
TRIAL REGISTRATION
ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .
Topics: Child; Pregnancy; Humans; Female; Polycystic Ovary Syndrome; Dysbiosis; RNA, Ribosomal, 16S; China; Fertilization in Vitro; Pregnancy Rate; Dietary Supplements; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38129882
DOI: 10.1186/s13063-023-07825-9 -
Trials Nov 2023Peritoneal dialysis (PD)-related infections, such as peritonitis, exit site, and tunnel infections, substantially impair the sustainability of PD. Accordingly,...
Multi-center, pragmatic, cluster-randomized, controlled trial of standardized peritoneal dialysis (PD) training versus usual care on PD-related infections (the TEACH-PD trial): trial protocol.
BACKGROUND
Peritoneal dialysis (PD)-related infections, such as peritonitis, exit site, and tunnel infections, substantially impair the sustainability of PD. Accordingly, PD-related infection is the top-priority research outcome for patients and caregivers. While PD nurse trainers teach patients to perform their own PD, PD training curricula are not standardized or informed by an evidentiary base and may offer a potential approach to prevent PD infections. The Targeted Education ApproaCH to improve Peritoneal Dialysis outcomes (TEACH-PD) trial evaluates whether a standardized training curriculum for PD nurse trainers and incident PD patients based on the International Society for Peritoneal Dialysis (ISPD) guidelines reduces PD-related infections compared to usual training practices.
METHODS
The TEACH-PD trial is a registry-based, pragmatic, open-label, multi-center, binational, cluster-randomized controlled trial. TEACH-PD will recruit adults aged 18 years or older who have not previously undergone PD training at 42 PD treatment units (clusters) in Australia and New Zealand (ANZ) between July 2019 and June 2023. Clusters will be randomized 1:1 to standardized TEACH-PD training curriculum or usual training practice. The primary trial outcome is the time to the first occurrence of any PD-related infection (exit site infection, tunnel infection, or peritonitis). The secondary trial outcomes are the individual components of the primary outcome, infection-associated catheter removal, transfer to hemodialysis (greater than 30 days and 180 days), quality of life, hospitalization, all-cause death, a composite of transfer to hemodialysis or all-cause death, and cost-effectiveness. Participants are followed for a minimum of 12 months with a targeted average follow-up period of 2 years. Participant and outcome data are collected from the ANZ Dialysis and Transplant Registry (ANZDATA) and the New Zealand Peritoneal Dialysis (NZPD) Registry. This protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.
DISCUSSION
TEACH-PD is a registry-based, cluster-randomized pragmatic trial that aims to provide high-certainty evidence about whether an ISPD guideline-informed standardized PD training curriculum for PD nurse trainers and adult patients prevents PD-related infections.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03816111. Registered on 24 January 2019.
Topics: Adult; Humans; Curriculum; Multicenter Studies as Topic; Peritoneal Dialysis; Peritonitis; Pragmatic Clinical Trials as Topic; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 37964367
DOI: 10.1186/s13063-023-07715-0 -
Pilot and Feasibility Studies Sep 2023Physical activity has been shown to benefit patients undergoing adjuvant cancer therapy. Although exercise interventions may be applied in several settings, most trials...
BACKGROUND
Physical activity has been shown to benefit patients undergoing adjuvant cancer therapy. Although exercise interventions may be applied in several settings, most trials have focused on specialized facilities for their interventions. While these approaches benefit the access for individuals living near exercise centers, it hampers the assessment of real-world effectiveness. Therefore, evaluating the feasibility and implementation of home-based models of exercise training, especially in low-to-middle-income settings, may inform future physical activity trials and programs. In this article, we present the protocol for the BENEFIT CA trial, which aims to assess the implementation of a remote exercise intervention for patients with breast cancer or prostate cancer, primarily quantifying adherence to an exercise program.
METHODS
This is a 12-week study, utilizing a non-randomized, single-arm design to assess the feasibility of a home-based exercise training. The intervention is remotely guided, and participants also receive an educational component about cancer and exercise. The study aims to recruit 40 patients diagnosed with breast cancer and 40 patients diagnosed with prostate cancer, all of whom undergoing active hormonal treatment. The primary outcome is the level of adherence, indicated as the proportion of performed exercise episodes. Secondary outcomes include recruitment rates, fatigue, quality of life, and functional capacity. Adverse events will be monitored throughout the study. Because this is a feasibility trial, the statistical analysis plan is based on descriptive statistics, which encompasses an intention-to-treat analysis and a plan for handling missing data.
DISCUSSION
This is a low-cost feasibility study to orient the design of a wide-range, pragmatic phase 3 trial based on remote exercise intervention. With this study, we aim to better understand the adherence and implementation strategies regarding home-based exercise for the proposed population and, in the near future, move forward to a randomized clinical trial. In addition, this trial may contribute to engage patients with cancer in exercise programs throughout their treatment and beyond.
TRIAL REGISTRATION
This trial has been approved by the Hospital de Clínicas de Porto Alegre Ethics Committee/IRB (48,869,621.9.0000.5327), and it is registered at Clinicaltrials.gov (NCT05258526), registered on February 25, 2022, prior to the beginning of the study.
PubMed: 37752564
DOI: 10.1186/s40814-023-01393-0 -
BMJ Open Aug 2023Improving access to effective contraception has the potential to reduce unintended pregnancy and abortion rates. Community pharmacists could play an expanded role in...
Expanding community pharmacists' scope of practice in relation to contraceptive counselling and referral: a protocol for a pragmatic, stepped-wedge, cluster randomised trial (ALLIANCE).
INTRODUCTION
Improving access to effective contraception has the potential to reduce unintended pregnancy and abortion rates. Community pharmacists could play an expanded role in contraceptive counselling and referral to contraceptive prescribers particularly when women are already attending community pharmacy to obtain emergency contraceptive pills (ECPs) or to have medical abortion (MA) medicines dispensed. The ALLIANCE trial aims to compare the subsequent uptake of effective contraception (hormonal or intrauterine) in women seeking ECP or MA medicines, who receive the ALLIANCE community pharmacy-based intervention with those who do not receive the intervention.
METHODS AND ANALYSIS
ALLIANCE is a stepped-wedge pragmatic cluster randomised trial in Australian community pharmacies. The ALLIANCE intervention involves community pharmacists delivering structured, patient-centred, effectiveness-based contraceptive counselling (and a referral to a contraceptive prescriber where appropriate) to women seeking either ECPs or to have MA medicines dispensed. Women participants will be recruited by participating pharmacists. A total of 37 pharmacies and 1554 participants will be recruited. Pharmacies commence in the control phase and are randomised to transition to the intervention phase at different time points (steps). The primary outcome is the self-reported use of effective contraception at 4 months; secondary outcomes include use of effective contraception and the rate of pregnancies or induced abortions at 12 months. A process and economic evaluation of the trial will also be undertaken.
ETHICS AND DISSEMINATION
Ethical approval has been obtained from the Monash University Human Research Ethics Committee (#34563). An explanatory statement will be provided and written consent will be obtained from all participants (pharmacy owner, pharmacist and women) before their commencement in the trial. Dissemination will occur through a knowledge exchange workshop, peer-reviewed journal publications, presentations, social media and conferences.
TRIAL REGISTRATION NUMBER
ACTRN12622001024730.
Topics: Female; Humans; Pregnancy; Australia; Contraceptive Agents; Counseling; Pharmacists; Referral and Consultation; Scope of Practice; Pragmatic Clinical Trials as Topic
PubMed: 37652588
DOI: 10.1136/bmjopen-2023-073154 -
JMIR Research Protocols Nov 2023Exergame-based motor-cognitive training in older adults has been associated with improvements in physical, cognitive, and psychological functioning. The novel Cocare...
Feasibility and Effectiveness of a Personalized Home-Based Motor-Cognitive Training Program in Community-Dwelling Older Adults: Protocol for a Pragmatic Pilot Randomized Controlled Trial.
BACKGROUND
Exergame-based motor-cognitive training in older adults has been associated with improvements in physical, cognitive, and psychological functioning. The novel Cocare system (Dividat GmbH), developed through a user-centered design process, allows motor-cognitive training in a telerehabilitation setting. It includes (1) a stationary stepping platform for supervised exergame training (Dividat Senso; Dividat GmbH), (2) a home-based version (Dividat Senso Flex, which is a rollable pressure-sensitive mat; Dividat GmbH), (3) an assessment system (including motor-cognitive tests), and (4) a rehabilitation cockpit for remote training supervision and management.
OBJECTIVE
The aim of this study is to test the feasibility and effectiveness of this novel training system.
METHODS
A total of 180 older adults from Switzerland, Italy, and Cyprus aged ≥60 years with a prescription for rehabilitation are randomly allocated to an intervention group or a control group. Both groups continue with their usual care, whereas participants in the intervention group additionally perform a 2-week supervised exergame training program at rehabilitation centers, followed by a 10-week home training program under remote supervision. The assessment system is used to indicate the start level of each participant, and, in both intervention periods, standardized progression rules are applied. The measures of feasibility include adherence, attrition, exergame enjoyment, willingness to perform such a training program, and the number and types of help requests. Effectiveness is assessed in terms of cognitive and physical functioning, balance confidence, and quality of life.
RESULTS
Data collection started in February 2023 and is ongoing. Final measurements are expected to be performed in January 2024.
CONCLUSIONS
Owing to the user-centered design approach, the Cocare system is expected to be user-friendly and offers several novel features to cover the whole continuum of care. This pragmatic trial will provide valuable information regarding final necessary adaptations and subsequent implementation efforts.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05751551; https://www.clinicaltrials.gov/study/NCT05751551.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/49377.
PubMed: 37943591
DOI: 10.2196/49377 -
BMC Medicine Mar 2024The increasing prevalence of gestational diabetes mellitus (GDM) is a major challenge, particularly in rural areas of China where control rates are suboptimal. This... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The increasing prevalence of gestational diabetes mellitus (GDM) is a major challenge, particularly in rural areas of China where control rates are suboptimal. This study aimed to evaluate the effectiveness of a GDM subsidy program in promoting GDM screening and management in these underserved regions.
METHODS
This multicenter, randomized controlled trial (RCT) was conducted in obstetric clinics of six rural hospitals located in three provinces in China. Eligible participants were pregnant women in 24-28 weeks' gestation, without overt diabetes, with a singleton pregnancy, access to a telephone, and provided informed consent. Participants were randomly assigned in a 1:1 ratio to either the intervention or control groups using an internet-based, computer-generated randomization system. The intervention group received subsidized care for GDM, which included screening, blood glucose retesting, and lifestyle management, with financial assistance provided to health care providers. In contrast, the control group received usual care. The primary outcomes of this study were the combined maternal and neonatal complications associated with GDM, as defined by the occurrence of at least one pre-defined complication in either the mother or newborn. The secondary outcomes included the GDM screening rate, rates of glucose retesting for pregnant women diagnosed with GDM, dietary patterns, physical activity levels, gestational weight gain, and antenatal visit frequency for exploratory purposes. Primary and secondary outcomes were obtained for all participants with and without GDM. Binary outcomes were analyzed by the generalized linear model with a link of logistic, and odds ratios (OR) with 95% confidence intervals (CIs) were reported. Count outcomes were analyzed by Poisson regression, and incidence rate ratios with 95% CIs were reported.
RESULTS
A total of 3294 pregnant women were randomly assigned to either the intervention group (n = 1649) or the control group (n = 1645) between 15 September 2018 and 30 September 2019. The proportion of pregnant women in the intervention group who suffered from combined maternal and/or neonatal complications was lower than in the control group with adjusted OR = 0.86 (0.80 to 0.94, P = 0.001), and a more significant difference was observed in the GDM subgroup (adjusted OR = 0.66, 95% CI 0.47 to 0.95, P = 0.025). No predefined safety or adverse events of ketosis or ketoacidosis associated with GDM management were detected in this study. Both the intervention and control groups had high GDM screening rates (intervention: 97.2% [1602/1649]; control: 94.5% [1555/1645], P < 0.001). Moreover, The intervention group showed a healthier lifestyle, with lower energy intake and more walking minutes (P values < 0.05), and more frequent blood glucose testing (1.5 vs. 0.4 visits; P = 0.001) compared to the control group.
CONCLUSION
In rural China, a GDM care program that provided incentives for both pregnant women and healthcare providers resulted in improved maternal and neonatal health outcomes. Public health subsidy programs in China should consider incorporating GDM screening and management to further enhance reproductive health.
TRIAL REGISTRATION
China Clinical Trials Registry ChiCTR1800017488. https://www.chictr.org.cn/.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Blood Glucose; China; Diabetes, Gestational; Dietary Patterns; Family
PubMed: 38443958
DOI: 10.1186/s12916-024-03330-1 -
Trials Jan 2024Robotic-assisted bronchoscopy has recently emerged as an alternative to electromagnetic navigational bronchoscopy for the evaluation of peripheral pulmonary lesions.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Robotic-assisted bronchoscopy has recently emerged as an alternative to electromagnetic navigational bronchoscopy for the evaluation of peripheral pulmonary lesions. While robotic-assisted bronchoscopy is proposed to have several advantages, such as an easier learning curve, it is unclear if it has comparable diagnostic utility as electromagnetic navigational bronchoscopy.
METHODS
Robotic versus Electromagnetic bronchoscopy for pulmonary LesIon AssessmeNT (RELIANT) is an investigator-initiated, single-center, open label, noninferiority, cluster randomized controlled trial conducted in two operating rooms at Vanderbilt University Medical Center. Each operating room (OR) is assigned to either robotic-assisted or electromagnetic navigational bronchoscopy each morning, with each OR day considered one cluster. All patients undergoing diagnostic bronchoscopy for evaluation of a peripheral pulmonary lesion in one of the two operating rooms are eligible. Schedulers, patients, and proceduralists are blinded to daily group allocations until randomization is revealed for each operating room each morning. The primary endpoint is the diagnostic yield defined as the proportion of cases yielding lesional tissue. Secondary and safety endpoints include procedure duration and procedural complications. Enrolment began on March 6, 2023, and will continue until 202 clusters have been accrued, with expected enrolment of approximately 400 patients by the time of completion in March of 2024.
DISCUSSION
RELIANT is a pragmatic randomized controlled trial that will compare the diagnostic yield of the two most commonly used bronchoscopic approaches for sampling peripheral pulmonary lesions. This will be the first known cluster randomized pragmatic trial in the interventional pulmonology field and the first randomized controlled trial of robotic-assisted bronchoscopy.
TRIAL REGISTRATION
ClinicalTrials.gov registration (NCT05705544) on January 30, 2023.
Topics: Humans; Bronchoscopy; Lung Neoplasms; Robotic Surgical Procedures; Lung; Electromagnetic Phenomena
PubMed: 38243291
DOI: 10.1186/s13063-023-07863-3 -
BMJ Surgery, Interventions, & Health... 2024Clinical trials of innovative neural implants are rapidly increasing and diversifying, but little is known about participants' post-trial access to the device and...
OBJECTIVES
Clinical trials of innovative neural implants are rapidly increasing and diversifying, but little is known about participants' post-trial access to the device and ongoing clinical care. This exploratory study examines common practices in the planning and coordination of post-trial access to neurosurgical devices. We also explore the perspectives of trial investigators on the barriers to post-trial access and ongoing care, as well as ethical questions related to the responsibilities of key stakeholder groups.
DESIGN SETTING AND PARTICIPANTS
Trial investigators (n=66) completed a survey on post-trial access in the most recent investigational trial of a surgically implanted neural device they had conducted. Survey respondents predominantly specialized in neurosurgery, neurology and psychiatry, with a mean of 14.8 years of experience working with implantable neural devices.
MAIN OUTCOME MEASURES
Outcomes of interest included rates of device explantation during or at the conclusion of the trial (pre-follow-up) and whether plans for post-trial access were described in the study protocol. Outcomes also included investigators' greatest 'barrier' and 'facilitator' to providing research participants with post-trial access to functional implants and perspectives on current arrangements for the sharing of post-trial responsibilities among key stakeholders.
RESULTS
Trial investigators reported either 'all' (64%) or 'most' (33%) trial participants had remained implanted after the end of the trial, with 'infection' and 'non-response' the most common reasons for explantation. When asked to describe the main barriers to facilitating post-trial access, investigators described limited funding, scarcity of expertise and specialist clinical infrastructure and difficulties maintaining stakeholder relationships. Notwithstanding these barriers, investigators overwhelmingly (95%) agreed there is an ethical obligation to provide post-trial access when participants individually benefit during the trial.
CONCLUSIONS
On occasions when devices were explanted during or at the end of the trial, this was done out of concern for the safety and well-being of participants. Further research into common practices in the post-trial phase is needed and essential to ethical and pragmatic discussions regarding stakeholder responsibilities.
PubMed: 38646454
DOI: 10.1136/bmjsit-2024-000262 -
Frontiers in Aging Neuroscience 2023Postoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and...
Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol.
INTRODUCTION
Postoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and mortality. A small number of trials have explored the role of S-ketamine in the treatment of POD due to its neuroprotective effects. Surprisingly, these trials have failed to yield supportive results. However, heterogeneity in delirium assessment methodologies, sample sizes, and outcome settings as well as deficiencies in S-ketamine use methods make the evidence provided by these studies less persuasive. Given the severe impact of POD on the health of elderly patients and the potential for S-ketamine to prevent it, we believe that designing a large sample size, and rigorous randomized controlled trial for further evaluation is necessary.
METHODS
This is a single-center, randomized, double-blind, placebo-controlled, pragmatic study. Subjects undergoing total hip or knee arthroplasty will be randomized in a 1:1 ratio to intervention ( = 186) and placebo ( = 186) groups. This trial aims to explore the potential role of S-ketamine in the prevention of POD. Its primary outcome is the incidence of POD within 3 postoperative days. Secondary outcomes include the number of POD episodes, the onset and duration of POD, the severity and subtype of POD, pain scores and opioid consumption, sleep quality, clinical outcomes, and safety outcomes.
DISCUSSION
To our knowledge, this is the first pragmatic study that proposes to use S-ketamine to prevent POD. We reviewed a large body of literature to identify potential preoperative confounding variables that may bias associations between the intervention and primary outcome. We will use advanced statistical methods to correct potential confounding variables, improving the test's power and external validity of test results. Of note, the patient population included in this trial will undergo intraspinal anesthesia. Although large, multicenter, randomized controlled studies have found no considerable difference in the effects of regional and general anesthesia on POD, patients receiving intraspinal anesthesia have less exposure to at-risk drugs, such as sevoflurane, propofol, and benzodiazepines, than patients receiving general anesthesia. At-risk drugs have been shown to negatively interfere with the neuroprotective effects of S-ketamine, which may be the reason for the failure of a large number of previous studies. There is currently a lack of randomized controlled studies evaluating S-ketamine for POD prevention, and our trial helps to fill a gap in this area.Trial registration: http://www.chictr.org.cn, identifier ChiCTR2300075796.
PubMed: 38099265
DOI: 10.3389/fnagi.2023.1298661