-
PloS One 2023Most adults in the UK experience at least one viral respiratory tract infection (RTI) per year. Individuals with comorbidities and those with recurrent RTIs are at...
Determining the clinical and cost-effectiveness of nasal sprays and a physical activity and stress management intervention to reduce respiratory tract infections in primary care: A protocol for the 'Immune Defence' randomised controlled trial.
BACKGROUND
Most adults in the UK experience at least one viral respiratory tract infection (RTI) per year. Individuals with comorbidities and those with recurrent RTIs are at higher risk of infections. This can lead to more severe illness, worse quality of life and more days off work. There is promising evidence that using common nasal sprays or improving immune function through increasing physical activity and managing stress, may reduce the incidence and severity of RTIs.
METHODS AND DESIGN
Immune Defence is an open, parallel group, randomised controlled trial. Up to 15000 adults from UK general practices, with a comorbidity or risk factor for infection and/or recurrent infections (3 or more infections per year) will be randomly allocated to i) a gel-based nasal spray designed to inhibit viral respiratory infections; ii) a saline nasal spray, iii) a digital intervention promoting physical activity and stress management, or iv) usual care with brief advice for managing infections, for 12 months. Participants will complete monthly questionnaires online. The primary outcome is the total number of days of illness due to RTIs over 6 months. Key secondary outcomes include: days with symptoms moderately bad or worse; days where work/normal activities were impaired; incidence of RTI; incidence of COVID-19; health service contacts; antibiotic usage; beliefs about antibiotics; intention to consult; number of days of illness in total due to respiratory tract infections over 12 months. Economic evaluation from an NHS perspective will compare the interventions, expressed as incremental cost effectiveness ratios. A nested mixed methods process evaluation will examine uptake and engagement with the interventions and trial procedures.
TRIAL STATUS
Recruitment commenced in December 2020 and the last participant is expected to complete the trial in April 2024.
DISCUSSION
Common nasal sprays and digital interventions to promote physical activity and stress management are low cost, accessible interventions applicable to primary care. If effective, they have the potential to reduce the individual and societal impact of RTIs.
TRIAL REGISTRATION
Prospectively registered with ISRCTN registry (17936080) on 30/10/2020.
SPONSOR
This RCT is sponsored by University of Southampton. The sponsors had no role in the study design, decision to publish, or preparation of the manuscript.
Topics: Adult; Humans; COVID-19; Nasal Sprays; Cost-Benefit Analysis; Quality of Life; Respiratory Tract Infections; Primary Health Care; Exercise; Randomized Controlled Trials as Topic
PubMed: 37450460
DOI: 10.1371/journal.pone.0285693 -
BMC Cancer Jul 2023Aromatase inhibitors (AI) are frequently used to treat hormone-receptor-positive breast cancer, but they have multiple adverse effects (e.g., osteoporosis, arthralgia),...
Promoting physical activity through supervised vs motivational behavior change interventions in breast cancer survivors on aromatase inhibitors (PAC-WOMAN): protocol for a 3-arm pragmatic randomized controlled trial.
BACKGROUND
Aromatase inhibitors (AI) are frequently used to treat hormone-receptor-positive breast cancer, but they have multiple adverse effects (e.g., osteoporosis, arthralgia), resulting in premature therapy discontinuation/switch. Physical activity (PA) can attenuate these negative effects and improve quality of life (QoL). However, most cancer survivors fail to perform/sustain adequate PA levels, especially in the long-term. Theory-based interventions, using evidence-based behavior change techniques, aimed at promoting long-term behavior change in breast cancer survivors are effective, but remain scarce and fail to promote self-regulatory skills and better-quality motivations associated with sustained PA adoption. This paper describes the design of the PAC-WOMAN trial, which will test the long-term effectiveness and cost-effectiveness of two state of the art, group-based interventions encouraging sustained changes in PA, sedentary behavior, and QoL. Additional aims include examining the impact of both interventions on secondary outcomes (e.g., body composition, physical function), and key moderators/mediators of short and long-term changes in primary outcomes.
METHODS
A 3-arm pragmatic randomized controlled trial, involving a 4-month intervention and a 12-month follow-up, will be implemented, in a real exercise setting, to compare: 1) brief PA counseling/motivational intervention; 2) structured exercise program vs. waiting-list control group. Study recruitment goal is 122 hormone-receptor-positive breast cancer survivors (stage I-III), on AI therapy (post-primary treatment completion) ≥ 1 month, ECOG 0-1. Outcome measures will be obtained at baseline, 4 months (i.e., post-intervention), 10 and 16 months. Process evaluation, analyzing implementation determinants, will also be conducted.
DISCUSSION
PAC-WOMAN is expected to have a relevant impact on participants PA and QoL and provide insights for the improvement of interventions designed to promote sustained adherence to active lifestyle behaviors, facilitating its translation to community settings.
TRIAL REGISTRATION
April 20, 2023 - NCT05860621. April 21, 2023 - https://doi.org/10.17605/OSF.IO/ZAQ9N April 27, 2023 - UMIN000050945.
Topics: Female; Humans; Cancer Survivors; Quality of Life; Breast Neoplasms; Aromatase Inhibitors; Motivation; Exercise; Randomized Controlled Trials as Topic
PubMed: 37407950
DOI: 10.1186/s12885-023-11137-1 -
Trials Nov 2023Extremely preterm infants have a high mortality and morbidity. Here, we present a statistical analysis plan for secondary Bayesian analyses of the pragmatic,... (Randomized Controlled Trial)
Randomized Controlled Trial
Detailed statistical analysis plan for a secondary Bayesian analysis of the SafeBoosC-III trial: a multinational, randomised clinical trial assessing treatment guided by cerebral oximetry monitoring versus usual care in extremely preterm infants.
BACKGROUND
Extremely preterm infants have a high mortality and morbidity. Here, we present a statistical analysis plan for secondary Bayesian analyses of the pragmatic, sufficiently powered multinational, trial-SafeBoosC III-evaluating the benefits and harms of cerebral oximetry monitoring plus a treatment guideline versus usual care for such infants.
METHODS
The SafeBoosC-III trial is an investigator-initiated, open-label, randomised, multinational, pragmatic, phase III clinical trial with a parallel-group design. The trial randomised 1601 infants, and the frequentist analyses were published in April 2023. The primary outcome is a dichotomous composite outcome of death or severe brain injury. The exploratory outcomes are major neonatal morbidities associated with neurodevelopmental impairment later in life: (1) bronchopulmonary dysplasia; (2) retinopathy of prematurity; (3) late-onset sepsis; (4) necrotising enterocolitis; and (5) number of major neonatal morbidities (count of bronchopulmonary dysplasia, retinopathy of prematurity, and severe brain injury). The primary Bayesian analyses will use non-informed priors including all plausible effects. The models will use a Hamiltonian Monte Carlo sampler with 1 chain, a sampling of 10,000, and at least 25,000 iterations for the burn-in period. In Bayesian statistics, such analyses are referred to as 'posteriors' and will be presented as point estimates with 95% credibility intervals (CrIs), encompassing the most probable results based on the data, model, and priors selected. The results will be presented as probability of any benefit or any harm, Bayes factor, and the probability of clinical important benefit or harm. Two statisticians will analyse the blinded data independently following this protocol.
DISCUSSION
This statistical analysis plan presents a secondary Bayesian analysis of the SafeBoosC-III trial. The analysis and the final manuscript will be carried out and written after we publicise the primary frequentist trial report. Thus, we can interpret the findings from both the frequentists and Bayesian perspective. This approach should provide a better foundation for interpreting of our findings.
TRIAL REGISTRATION
ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.
Topics: Infant; Infant, Newborn; Humans; Infant, Extremely Premature; Oximetry; Bayes Theorem; Retinopathy of Prematurity; Bronchopulmonary Dysplasia; Cerebrovascular Circulation; Brain Injuries
PubMed: 37974280
DOI: 10.1186/s13063-023-07720-3 -
Trials Apr 2024To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In... (Randomized Controlled Trial)
Randomized Controlled Trial
Prednisolone Versus Colchicine for Acute Gout in Primary Care: statistical analysis plan for the pragmatic, multicenter, randomized, and double-blinded COPAGO non-inferiority trial.
BACKGROUND
To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen.
STUDY DESIGN
This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed.
STATISTICAL ANALYSIS PLAN
N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0-10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients' global assessment of treatment success are secondary outcomes.
DISCUSSION
The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).
Topics: Humans; Arthritis, Gouty; Colchicine; Gout; Pain; Prednisolone; Primary Health Care; Prospective Studies; Treatment Outcome; Male; Female
PubMed: 38570873
DOI: 10.1186/s13063-024-08066-0 -
Nutrients Sep 2023In-person culinary medicine (CM) can improve health behaviors, but its translation to virtual platforms and impact on diabetes outcomes are not well described. We... (Randomized Controlled Trial)
Randomized Controlled Trial
Redesigning Recruitment and Engagement Strategies for Virtual Culinary Medicine and Medical Nutrition Interventions in a Randomized Trial of Patients with Uncontrolled Type 2 Diabetes.
In-person culinary medicine (CM) can improve health behaviors, but its translation to virtual platforms and impact on diabetes outcomes are not well described. We designed a pragmatic trial comparing the effectiveness of virtual CM (eCM) to Medical Nutrition Therapy on diabetes outcomes among patients with uncontrolled diabetes within a safety-net healthcare system. All participants were provided cooking equipment and food from a food pantry. Due to low initial eCM participation, recruitment was paused, and eight semi-structured interviews were conducted to solicit feedback on study appeal, operations, and barriers to participation. Rapid thematic analysis was used to modify study operations. We found that participants were interested in the study and motivated by health concerns. While they valued food distribution and cooking equipment, they highlighted transportation barriers and conflicts with the pick-up time/location. Some eCM participants expressed discomfort with the virtual platform or preferred to observe rather than cook along. Study operations were modified by (1) moving supply pick-up to a familiar community clinic and diversifying food pick-up locations; (2) offering an in-person orientation to the program to increase comfort with the virtual platform; (3) emphasizing the credibility and relatability of the eCM instructor and encouraging participation of family members. This redesign led to the recruitment of 79 participants, of whom 75% attended at least one class. In conclusion, participant feedback informed pragmatic changes in study operations that increased engagement in this ongoing trial and may inform future eCM program design.
Topics: Humans; Diabetes Mellitus, Type 2; Food; Nutrition Therapy; Cooking; Ambulatory Care Facilities
PubMed: 37836408
DOI: 10.3390/nu15194124 -
OTA International : the Open Access... Dec 2023Patient engagement in the design and implementation of clinical trials is necessary to ensure that the research is relevant and responsive to patients. The PREP-IT...
OBJECTIVES
Patient engagement in the design and implementation of clinical trials is necessary to ensure that the research is relevant and responsive to patients. The PREP-IT trials, which include 2 pragmatic trials that evaluate different surgical preparation solutions in orthopaedic trauma patients, followed the patient-centered outcomes research (PCOR) methodology throughout the design, implementation, and conduct. We conducted a substudy within the PREP-IT trials to explore participants' experiences with trial participation.
METHODS
At the final follow-up visit (12 months after their fracture), patients participating in the PREP-IT trials were invited to participate in the substudy. After providing informed consent, participants completed a questionnaire that asked about their experience and satisfaction with participating in the PREP-IT trials. Descriptive statistics are used to report the findings.
RESULTS
Four hundred two participants participated in the substudy. Most participants (394 [98%]) reported a positive experience, and 376 (94%) participants felt their contributions were appreciated. The primary reasons for participation were helping future patients with fracture (279 [69%]) and to contribute to science (223 [56%]). Two hundred seventeen (46%) participants indicated that their decision to participate was influenced by the minimal time commitment.
CONCLUSIONS
Most participants reported a positive experience with participating in the PREP-IT trials. Altruism was the largest motivator for participating in this research. Approximately half of the participants indicated that the pragmatic, low-participant burden design of the trial influenced their decision to participate. Meaningful patient engagement, a pragmatic, and low-burden protocol led to high levels of participant satisfaction.
PubMed: 37860179
DOI: 10.1097/OI9.0000000000000287 -
BMC Medical Research Methodology Oct 2023Selecting and collecting data to support appropriate primary and secondary outcomes is a critical step in designing trials that can change clinical practice. In this...
INTRODUCTION
Selecting and collecting data to support appropriate primary and secondary outcomes is a critical step in designing trials that can change clinical practice. In this study, we aimed to investigate who contributes to the process of selecting and collecting trial outcomes, and how these people are involved. This work serves two main purposes: (1) it provides the trials community with evidence to demonstrate how outcomes are currently selected and collected, and (2) it allows people involved in trial design and conduct to pick apart these processes to consider how efficiencies and improvements can be made.
METHODS
One-with-one semi-structured interviews, supported by a topic guide to ensure coverage of key content. The Framework approach was used for thematic analysis of data, and themes were linked through constant comparison of data both within and across participant groups. Interviews took place between July 2020 and January 2021. Participants were twenty-nine international trialists from various contributor groups, working primarily on designing and/or delivering phase III pragmatic effectiveness trials. Their experience spanned various funders, trial settings, clinical specialties, intervention types, and participant populations.
RESULTS
We identified three descriptive themes encompassing the process of primary and secondary outcome selection, collection, and the publication of outcome data. Within these themes, participants raised issues around the following: 1) Outcome selection: clarity of the research question; confidence in selecting trial outcomes and how confidence decreases with increased experience; interplay between different interested parties; how patients and the public are involved in outcome selection; perceived impact of poor outcome selection including poor recruitment and/or retention; and use of core outcome sets. 2) Outcome collection: disconnect between decisions made by outcome selectors and the practical work done by outcome collectors; potential impact of outcome measures on trial participants; potential impact on trial staff workload; and use of routinely collected data. 3) Publication of outcome data: difficulties in finding time to write and revise manuscripts for publication due to time and funding constraints. Participants overwhelmingly focused on the process of outcome selection, a topic they talked about unprompted. When prompted, participants do discuss outcome collection, but poor communication between selectors and collectors at the trial design stage means that outcome selection is rarely linked with the data collection workload it generates.
DISCUSSION
People involved in the design and conduct of trials fail to connect decisions around outcome selection with data collection workload. Publication of outcome data and effective dissemination of trial results are hindered due to the project-based culture of some academic clinical trial research.
Topics: Humans; Qualitative Research; Outcome Assessment, Health Care; Data Collection
PubMed: 37821867
DOI: 10.1186/s12874-023-02054-9 -
Trials Jun 2024Randomized controlled trials (RCTs) are rigorous scientific research designs for evaluating intervention effectiveness. However, implementing RCTs in a real-world...
Strengths, challenges, and strategies for implementing pragmatic multicenter randomized controlled trials (RCTs): example of the Personalized Citizen Assistance for Social Participation (APIC) trial.
BACKGROUND
Randomized controlled trials (RCTs) are rigorous scientific research designs for evaluating intervention effectiveness. However, implementing RCTs in a real-world context is challenging. To develop strategies to improve its application, it is essential to understand the strengths and challenges of this design. This study thus aimed to explore the strengths, challenges, and strategies for improving the implementation of a pragmatic multicenter, prospective, two-arm RCT evaluating the effects of the Personalized Citizen Assistance for Social Participation (Accompagnement-citoyen Personnalisé d'Intégration Communautaire: APIC; weekly 3-h personalized stimulation sessions given by a trained volunteer over a 12-month period) on older adults' health, social participation, and life satisfaction.
METHODS
A multiple case study was conducted with 14 participants, comprising one research assistant, seven coordinators, and six managers of six community organizations serving older adults, who implemented the APIC in the context of a RCT. Between 2017 and 2023, qualitative data were extracted from 24 group meetings, seven semi-directed interviews, emails exchanged with the research team, and one follow-up document.
RESULTS
Aged between 30 and 60 (median ± SIQR: 44.0 ± 6.3), most participants were women from organizations already offering social participation interventions for older adults and working with the public sector. Reported strengths of this RCT were its relevance in assessing an innovative intervention to support healthy aging, and the sharing of common goals, expertise, and strategies with community organizations. Challenges included difficulties recruiting older adults, resistance to potential control group assignments, design complexity, and efforts to mobilize and engage volunteers. The COVID-19 pandemic lockdown and health measures exacerbated challenges related to recruiting older adults and mobilizing volunteers and complicated delivery of the intervention. The strategies that mostly overcame difficulties in recruiting older adults were reducing sample size, simplifying recruitment procedures, emphasizing the health follow-up, extending partnerships, and recognizing and supporting volunteers better. Because of the lockdown and physical distancing measures, the intervention was also adapted for remote delivery, including via telephone or videoconferencing.
CONCLUSION
Knowledge of the strengths and challenges of pragmatic RCTs can contribute to the development of strategies to facilitate implementation studies and better evaluate health and social participation interventions delivered under real-life conditions.
TRIAL REGISTRATION
NCT03161860; Pre-results. Registered on May 22, 2017.
Topics: Humans; Social Participation; Female; Male; Middle Aged; Prospective Studies; Adult; Volunteers; Research Design; COVID-19; Randomized Controlled Trials as Topic; Pragmatic Clinical Trials as Topic; Aged; Personal Satisfaction; Multicenter Studies as Topic
PubMed: 38937798
DOI: 10.1186/s13063-024-08248-w -
Trials Aug 2023Arts therapies are widely but inconsistently provided in community mental health. Whilst they are appealing to patients, evidence for their effectiveness is mixed....
Effectiveness of group arts therapies (art therapy, dance movement therapy and music therapy) compared to group counselling for diagnostically heterogeneous psychiatric community patients: study protocol for a randomised controlled trial in mental health services (the ERA study).
BACKGROUND
Arts therapies are widely but inconsistently provided in community mental health. Whilst they are appealing to patients, evidence for their effectiveness is mixed. Trials to date have been limited to one art-form or diagnosis. Patients may hold strong preferences for or against an art-form whilst group therapies rely on heterogeneity to provide a range of learning experiences. This study will test whether manualised group arts therapies (art therapy, dance movement therapy and music therapy) are effective in reducing psychological distress for diagnostically heterogeneous patients in community mental health compared to active group counselling control.
METHODS
A pragmatic multi-centre 2-arm randomised controlled superiority trial with health economic evaluation and nested process evaluation. Adults aged ≥ 18, living in the community with a primary diagnosis of psychosis, mood, or anxiety disorder will be invited to participate and provide written informed consent. Participants are eligible if they score ≥ 1.65 on the Global Severity Index of the Brief Symptom Inventory. Those eligible will view videos of arts therapies and be asked for their preference. Participants are randomised to either their preferred type of group arts therapy or counselling. Groups will run twice per week in a community venue for 20 weeks. Our primary outcome is symptom distress at the end of intervention. Secondary outcomes include observer-rated symptoms, social situation and quality of life. Data will be collected at baseline, post-intervention and 6 and 12 months post-intervention. Outcome assessors and trial statisticians will be blinded. Analysis will be intention-to-treat. Economic evaluation will assess the cost-effectiveness of group arts therapies. A nested process evaluation will consist of treatment fidelity analysis, exploratory analysis of group process measures and qualitative interviews with participants and therapists.
DISCUSSION
This will be the first trial to account for patient preferences and diagnostic heterogeneity in group arts therapies. As with all group therapies, there are a number of logistical challenges to which we have had to further adapt due to the COVID-19 pandemic. Overall, the study will provide evidence as to whether there is an additive benefit or not to the use of the arts in group therapy in community mental health care.
TRIAL REGISTRATION
ISRCTN, ISRCTN88805048 . Registered on 12 September 2018.
Topics: Adult; Humans; Art Therapy; Counseling; COVID-19; Dance Therapy; Mental Health Services; Multicenter Studies as Topic; Music Therapy; Pandemics; Quality of Life; Randomized Controlled Trials as Topic; Adolescent; Pragmatic Clinical Trials as Topic; Equivalence Trials as Topic
PubMed: 37626418
DOI: 10.1186/s13063-023-07232-0 -
Trials Aug 2023In the last decades, noninvasive ventilation (NIV) has been increasingly used to support patients with hypercapnic and hypoxemic acute respiratory failure. Pressure... (Randomized Controlled Trial)
Randomized Controlled Trial
A pragmatic, open-label, multi-center, randomized controlled clinical trial on the rotational use of interfaces vs standard of care in patients treated with noninvasive positive pressure ventilation for acute hypercapnic respiratory failure: the ROTAtional-USE of interface STUDY (ROTA-USE STUDY).
BACKGROUND
In the last decades, noninvasive ventilation (NIV) has been increasingly used to support patients with hypercapnic and hypoxemic acute respiratory failure. Pressure ulcers are a frequently observed NIV-related adverse effect, directly related to interface type and exposure time. Switching to a different interface has been proposed as a solution to improve patient comfort. However, large studies investigating the benefit of this strategy are not available. Thus, the aim of the ROTAtional-USE of interface STUDY (ROTA-USE STUDY) is to investigate whether a protocolized rotational use of interfaces during NIV is effective in reducing the incidence of pressure ulcers.
METHODS
The ROTA-USE STUDY is a pragmatic, parallel arm, open-label, multicenter, spontaneous, non-profit, randomized controlled trial requiring non-significant risk medical devices, with the aim to determine whether a rotational strategy of NIV interfaces is associated with a lower incidence of pressure ulcers compared to the standard of care. In the intervention group, NIV mask will be randomly chosen and rotated every 6 h. In the control group, mask will be chosen according to the standard of care of the participating centers and changed in case of discomfort or in the presence of new pressure sores. In both groups, the skin underneath the mask will be inspected every 12 h for any possible damage by blinded assessors. The primary outcome is the proportion of patients developing new pressure sores at 36 h from randomization. The secondary outcomes are (i) onset of pressure sores measured at different time points, i.e., 12, 24, 36, 48, 60, 72, 84, and 96 h; (ii) number and stage of pressure sores and comfort measured at 12, 24, 36, 48, 60, 72, 84, and 96 h; and (iii) the economic impact of the protocolized rotational use of interfaces. A sample size of 239 subjects per group (intervention and control) is estimated to detect a 10% absolute difference in the proportion of patients developing pressure sores at 36 h.
DISCUSSION
The development of pressure ulcers is a common side effect of NIV that negatively affects the patients' comfort and tolerance, often leading to NIV failure and adverse outcomes. The ROTA-USE STUDY will determine whether a protocolized rotational approach can reduce the incidence, number, and severity of pressure ulcers in NIV-treated patients.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05513508. Registered on August 24, 2022.
Topics: Humans; Noninvasive Ventilation; Positive-Pressure Respiration; Pressure Ulcer; Respiratory Insufficiency; Standard of Care; Adult; Treatment Outcome
PubMed: 37574558
DOI: 10.1186/s13063-023-07560-1