Parallel-group Randomized Controlled Trials Research Articles

Randomised, controlled, feasibility trial comparing vasopressor infusion administered via peripheral cannula versus central venous catheter for critically ill adults: A study protocol.

When clinicians need to administer a vasopressor infusion, they are faced with the choice of administration via either peripheral intravenous catheter (PIVC) or central venous catheter (CVC). Vasopressor infusions have traditionally been administered via central venous catheters (CVC) rather than Peripheral Intra Venous Catheters (PIVC), primarily due to concerns of extravasation and resultant tissue injury. This practice is not guided by contemporary randomised controlled trial (RCT) evidence. Observational data suggests safety of vasopressor infusion via PIVC. To address this evidence gap, we have designed the "Vasopressors Infused via Peripheral or Central Access" (VIPCA) RCT. The VIPCA trial is a single-centre, feasibility, parallel-group RCT. Eligible critically ill patients requiring a vasopressor infusion will be identified by emergency department (ED) or intensive care unit (ICU) staff and randomised to receive vasopressor infusion via either PIVC or CVC. Primary outcome is feasibility, a composite of recruitment rate, proportion of eligible patients randomised, protocol fidelity, retention and missing data. Primary clinical outcome is days alive and out of hospital up to day-30. Secondary outcomes will include safety and other clinical outcomes, and process and cost measures. Specific aspects of safety related to vasopressor infusions such as extravasation, leakage, device failure, tissue injury and infection will be assessed. VIPCA is a feasibility RCT whose outcomes will inform the feasibility and design of a multicentre Phase-3 trial comparing routes of vasopressor delivery. The exploratory economic analysis will provide input data for the full health economic analysis which will accompany any future Phase-3 RCT.

Effectiveness and uptake of a transdiagnostic emotion regulation mobile intervention among university students: Protocol for a randomized controlled trial

BackgroundGoing to university is a major life event, which can be stressful and negatively affect mental health. However, it also presents an opportunity to establish a foundation for positive life trajectories. To support university students, a mobile transdiagnostic emotion regulation (ER) intervention has been developed, offering both broad-based (universal) and targeted (indicated) preventative support. ER, a transdiagnostic factor underlying various mental health problems, is a critical intervention target in students, a demographic particularly susceptible to mental health issues. Cultivating ER can help manage immediate stressors and foster long-term wellbeing. This paper describes the study protocol for a Randomized Controlled Trial (RCT) evaluating the effectiveness and uptake of such mobile transdiagnostic ER intervention. MethodThe superiority parallel-group RCT involves 250 participants randomized to either the intervention condition (i.e., full access to the mobile intervention, n = 125) or to a waitlist control condition (n = 125). Primary outcomes include ER skills and stress symptoms. Secondary outcomes include mental health parameters (anxiety, depression, resilience) and intervention uptake (i.e., objective engagement, subjective engagement, ER skills application in real life). Outcomes are assessed at baseline, week 3, 8 and 12, with continuous log-data collection for user engagement. DiscussionThis study evaluates the effectiveness and uptake of a transdiagnostic ER mobile intervention for the student population addressing their ER developmental needs. If successful, the results will validate our approach to intervention development and whether focusing on learning transfer (i.e., application of the learnt skills in real-life) and personalization using a recommendation system, can boost the real-world application of skills and intervention impact.

Feasibility, acceptability, and initial efficacy of a wheelchair exercise training program in persons with multiple sclerosis: study protocol for a parallel group randomized controlled trial

Purpose: This study is a randomized controlled trial (RCT) that examines the feasibility, acceptability, and initial efficacy of a home-based, remotely supported and supervised exercise training program that was developed using a three-step community engaged research process for persons with multiple sclerosis (MS) who are wheelchair users.Materials and Methods: The study design is a parallel group RCT (NCT05888727). We aim to enroll 24 wheelchair users with MS who will be randomly assigned using REDCap randomization module into exercise training or attention/contact wellness control conditions. The conditions will be delivered remotely over 16 weeks and supported using online, one-onone behavioral coaching. The feasibility outcomes of interest include recruitment and retention rates, and safety outcomes collected throughout the study period. The acceptability outcomes include participant satisfaction and perceptions measured using formative surveys and interviews following the 16-week period. Efficacy outcomes include metabolic health, MS symptoms, and exercise behavior measured before and after the 16-week period. The data analysis will follow intent-to-treat principles using 2 group by 2 time mixed factor ANOVA with estimation of Cohen’s d values as effect sizes.Conclusions: The results will guide future research targeting health outcomes using exercise training among wheelchair users with MS who have largely been absent from health promotion research.

Oxytocin-induced increases in cytokines and clinical effect on the core social features of autism: Analyses of RCT datasets

Although oxytocin may provide a novel therapeutics for the core features of autism spectrum disorder (ASD), previous results regarding the efficacy of repeated or higher dose oxytocin are controversial, and the underlying mechanisms remain unclear. The current study is aimed to clarify whether repeated oxytocin alter plasma cytokine levels in relation to clinical changes of autism social core feature. Here we analyzed cytokine concentrations using comprehensive proteomics of plasmas of 207 adult males with high-functioning ASD collected from two independent multi-center large-scale randomized controlled trials (RCTs): Testing effects of 4-week intranasal administrations of TTA-121 (A novel oxytocin spray with enhanced bioavailability: 3U, 6U, 10U, or 20U/day) and placebo in the crossover discovery RCT; 48U/day Syntocinon or placebo in the parallel-group verification RCT. Among the successfully quantified 17 cytokines, 4 weeks TTA-121 6U (the peak dose for clinical effects) significantly elevated IL-7 (9.74, 95 % confidence interval [CI] 3.59 to 15.90, False discovery rate corrected P (PFDR) < 0.001), IL-9 (56.64, 20.46 to 92.82, PFDR < 0.001) and MIP-1b (18.27, 4.96 to 31.57, PFDR < 0.001) compared with placebo. Inverted U-shape dose–response relationships peaking at TTA-121 6U were consistently observed for all these cytokines (IL-7: P < 0.001; IL-9: P < 0.001; MIP-1b: P = 0.002). Increased IL-7 and IL-9 in participants with ASD after 4 weeks TTA-121 6U administration compared with placebo was verified in the confirmatory analyses in the dataset before crossover (PFDR < 0.001). Furthermore, the changes in all these cytokines during 4 weeks of TTA-121 10U administration revealed associations with changes in reciprocity score, the original primary outcome, observed during the same period (IL-7: Coefficient = −0.05, −0.10 to 0.003, P = 0.067; IL-9: −0.01, −0.02 to −0.003, P = 0.005; MIP-1b: −0.02, −0.04 to −0.007, P = 0.005). These findings provide the first evidence for a role of interaction between oxytocin and neuroinflammation in the change of ASD core social features, and support the potential role of this interaction as a novel therapeutic seed.Trial registration: UMIN000015264, NCT03466671/UMIN000031412.

A Suprapatellar approach, when compared to an Infrapatellar approach, yields less Anterior Knee Pain and better patellofemoral joint Function, for intramedullary nailing of diaphyseal tibial fractures. Results of a Randomised Controlled Trial.

To assess if a suprapatellar (SP) approach, when compared to an infrapatellar (IP) approach, yielded less patient reported anterior knee pain and higher patellofemoral joint function at 6 weeks and 12 months post operatively, when treating tibial fractures with intramedullary nailing. Prospective, parallel group randomized control trial. Tertiary level one trauma care centre, Brisbane, Australia. Skeletally mature patients with an acute diaphyseal tibial fracture (AO/OTA 41A2/3, 42 A1- 43A3) amenable to an IMN were included. Exclusion criteria were peri-prosthetic fractures, nonunions, and presence of a contralateral injury that would restrict weightbearing. Anterior knee pain, through the visual analogue scale (VAS) and patellofemoral function using the Kujala scale at 6-weeks and 12-months were compared between those treated with a SP and IP approach. 95 tibia fractures were included in the randomized trial, with complete follow-up data for 44 and 46 tibia fractures in the SP and IP groups, respectively. The SP cohort exhibited better patella-femoral knee function at both 6 weeks post operatively (Kajula 53.0 for SP vs 43.2 for IP, p<0.01)) and 12 months (Kujala 92.0 for SP vs 81.3 for IP (p<0.01)), and a reduction in anterior knee pain at 12-months post-operatively (VAS 0.7 SP vs 2.9 IP, p<0.01). This randomized trial demonstrated clinically meaningful differences in patellofemoral function, for a suprapatellar versus infrapatellar approach, with a greater than 10 point discrepancy in Kujala score at both 6 weeks and 12 months. Additionally, there was a clinically important difference in VAS knee pain scores for patients at 12 months, but not at 6 weeks, post operatively. These results contribute to the growing body of evidence demonstrating the functional and clinical benefits of the suprapatellar approach.

Mobile health biometrics to prescribe immediate remote physical activity for enhancing uptake to cardiac rehabilitation (MOTIVATE-CR+): protocol for a randomised controlled feasibility trial

IntroductionCardiac rehabilitation (CR) can reduce cardiovascular mortality and improve health-related quality of life. In the United Kingdom, patient uptake of CR remains low (52%), falling well short of the target...

Bathing Adaptations in the Homes of Older Adults (BATH-OUT-2): study protocol for a randomised controlled trial, economic evaluation and process evaluation

BackgroundThe onset of disability in bathing is particularly important for older adults as it can be rapidly followed by disability in other daily activities; this may represent a judicious time point for intervention in order to improve health, well-being and associated quality of life. An important environmental and preventative intervention is housing adaptation, but there are often lengthy waiting times for statutory provision. In this randomised controlled trial (RCT), we aim to evaluate the effectiveness and cost-effectiveness of bathing adaptations compared to no adaptations and to explore the factors associated with routine and expedited implementation of bathing adaptations.MethodsBATH-OUT-2 is a multicentre, two-arm, parallel-group RCT. Adults aged 60 and over who are referred to their local authority for an accessible level access shower will be randomised, using pairwise randomisation, 1:1, to receive either an expedited provision of an accessible shower via the local authority or a usual care control waiting list. Participants will be followed up for a maximum of 12 months and will receive up to four follow-ups in this duration. The primary outcome will be the participant’s physical well-being, assessed by the Physical Component Summary score of the Short Form-36 (SF-36), 4 weeks after the intervention group receives the accessible shower. The secondary outcomes include the Mental Component Summary score of the SF-36, self-reported falls, health and social care resource use, health-related quality of life (EQ-5D-5L), social care-related quality of life (Adult Social Care Outcomes Toolkit (ASCOT)), fear of falling (Short Falls Efficacy Scale), independence in bathing (Barthel Index bathing question), independence in daily activities (Barthel Index) and perceived difficulty in bathing (0–100 scale). A mixed-methods process evaluation will comprise interviews with stakeholders and a survey of local authorities with social care responsibilities in England.DiscussionThe BATH-OUT-2 trial is designed so that the findings will inform future decisions regarding the provision of bathing adaptations for older adults. This trial has the potential to highlight, and then reduce, health inequalities associated with waiting times for bathing adaptations and to influence policies for older adults.Trial registrationISRCTN Registry ISRCTN48563324. Prospectively registered on 09/04/2021.

Train to sustain: a randomised controlled trial evaluation of a vitality training employing behaviour-change techniques.

This paper reports on the effects of a 9-week vitality training that employed behaviour-change techniques and was evaluated using a randomised controlled trial (RCT) in three large companies based in the Netherlands. A total of 84 adult employees from three participating organisations in the Netherlands were enrolled in the study. A parallel group RCT design was employed and participants were assigned using individual random assignment to either an intervention (n = 38) or a waitlist control group (n = 46). The intervention consisted of a 9-week vitality training employing the behaviour-change techniques of self-persuasion, implementation intentions, and self-efficacy, which was delivered in-house over five fortnightly 2-hour sessions. Primary outcomes (i.e., reported energy and stress) and secondary outcomes (i.e., reported daily life satisfaction and work capacity) were assessed prior to, immediately after, and 3 months following the intervention. A mixed MANOVA revealed a significant interaction effect between treatment group and time period for the combination of reported energy, stress, daily life satisfaction, and work capacity. Subsequent univariate ANOVAs revealed significant interactions between treatment group and time period for reported energy, stress, and daily life satisfaction; however, not for reported work capacity. Improvements in outcomes were observed for both groups following their completion of the vitality training; however, not all improvements reached statistical significance. Reported self-efficacy regarding managing work-life balance was found to mediate the relationship between the effects of the intervention and reported energy; however, such an effect was not found for stress. An intervention drawing upon evidence-based behaviour-change techniques shows promise for improving indicators associated with burnout; although, it is recommended that in future research a larger-scale evaluation be conducted over a longer time period with an active control group to establish effectiveness.Clinical trial registration: https://www.anzctr.org.au/, ACTRN12622001268730.

Efficacy of an individual-tailored smoking cessation intervention APP among Chinese smokers: study protocol for a randomized controlled trial

Background and aimsTobacco use has posed a tremendous public health problem for China. The Chinese government has taken great efforts to curb the tobacco epidemic. However, the existing smoking cessation services available in China are underused and have some limitations. Our research team intends to develop a smartphone smoking cessation application (SSC APP) and integrate it with the existing smoking cessation services. This study aims to assess the efficacy of the SSC APP developed by our research team through a randomized controlled trial (RCT).MethodsCurrent smokers who are motivated to quit within 1 month (n = 1000) will be recruited both online and offline, and all potential participants will register and complete the prescreening assessment online. Participants will be randomly assigned to either the intervention group (receiving the SSC APP and a self-help smoking cessation manual) or the control group (receiving a self-help smoking cessation manual only) using a block randomization method. This study will be a two-arm, single-blind, parallel-group RCT. Participants will be followed up after enrollment through online questionnaires or by phone call. The primary outcome is self-reported 6-month continuous abstinence. The main secondary outcomes include self-reported 7-day point-prevalence abstinence at each follow-up; self-reported 3-month continuous abstinence; reduction in the number of cigarettes smoked per day; and the number of recent quit attempts.DiscussionIf this SSC APP proves to be effective, it could be integrated with the existing smoking cessation services and further facilitate smoking cessation at the population level in China.Trial registrationChinese Clinical Trial Registry: ChiCTR2200062097, Registered July 22, 2022.

Abstracts of randomized controlled trials in pediatric dentistry: reporting quality and spin

Backgrounds provide readers a concise and readily accessible information of the trials. However, poor reporting quality and spin (misrepresentation of research findings) can lead to an overestimation in trial validity. This methodological study aimed to assess the reporting quality and spin among randomized controlled trial (RCT) abstracts in pediatric dentistry.MethodsWe hand-searched RCTs in five leading pediatric dental journals between 2015 and 2021. Reporting quality in each abstract was assessed using the original 16-item CONSORT for abstracts checklist. Linear regression analyses were performed to identify factors associated with reporting quality. We evaluated the presence and characteristics of spin only in abstracts of parallel-group RCTs with nonsignificant primary outcomes according to pre-determined spin strategies.ResultsOne hundred eighty-two abstracts were included in reporting quality evaluation. The mean overall quality score was 4.57 (SD, 0.103; 95% CI, 4.36–4.77; score range, 1–10). Only interventions, objective, and conclusions were adequately reported. Use of flow diagram (P < 0.001) was the only significant factor of higher reporting quality. Of the 51 RCT abstracts included for spin analysis, spin was identified in 40 abstracts (78.4%), among which 23 abstracts (45.1%) had spin in the Results section and 39 in the Conclusions Sect. (76.5%).ConclusionsThe reporting quality of RCT abstracts in pediatric dentistry is suboptimal and the prevalence of spin is high. Joint efforts are needed to improve reporting quality and minimize spin.

Study Protocol: Role of Intermittent Fasting on Disease Severity and Quality of Life in Psoriasis and Psoriatic Arthritis: A Single-Blind Parallel Group Randomized Control Trial

BACKGROUND Psoriasis and psoriatic arthritis (PsA) have a strong association with obesity and metabolic syndrome. Despite patient interest in non-pharmacologic methods to treat psoriasis and manage overall health, there is insufficient data available to guide dietary counseling. OBJECTIVE This study aims to identify the role of a popular anti-inflammatory diet known as intermittent fasting (IF) in psoriasis and psoriatic arthritis (PsA). METHODS A single-blind parallel group randomized control trial will be performed in 60 patients who have been diagnosed with psoriasis or PsA. Patients will be assigned 1:1 to either the IF group or control group. Patients assigned to the IF group will follow a 16:8 fasting IF method for the first 12 weeks, followed by the resumption of their routine diet. Patients assigned to the control group will follow their routine diet for 24 weeks. RESULTS A total of 24 patients have been enrolled in our study, with a final enrollment goal of 60 patients. The final visit is foreseen for July 2023. CONCLUSIONS This study aims to identify the role of a popular anti-inflammatory diet known as intermittent fasting (IF) in the management of psoriasis and PsA. Publishing this data will allow all dermatologists and the National Psoriasis Foundation to provide a consistent, evidence-based recommendation for IF as a potential non-pharmacologic intervention for patients with psoriasis and psoriatic arthritis (PsA).

O-033 A randomised control trial of an online decision-aid for women considering elective egg-freezing

Abstract Study question Does a Decision-Aid for those considering elective egg-freezing impact decisional conflict, the decision-making process, and quality of the decision made, compared to existing information? Summary answer The Decision-Aid significantly reduced decisional conflict and improved preparedness for decision-making. What is known already Elective egg-freezing offers women the potential to extend their reproductive years. The decision to freeze eggs is complex, and our previous data shows that 78% of women had high decisional conflict (uncertainty) when they considered elective egg-freezing. Decision-Aids are the gold-standard for supporting complex health-related decisions. They have been shown to reduce decisional conflict and improve knowledge, risk perception, and decision alignment with personal values, when compared to standard care alone across a range of health conditions. We developed an online Decision-Aid to support women considering elective egg-freezing. Study design, size, duration A single-blinded, two-arm parallel group Randomised Control Trial. Participants were recruited September 2020-March 2021 (target n = 286). Randomisation was 1:1 to the intervention (Decision-Aid plus existing information) or control (existing information only) group, stratified by Australian state/territory and prior consultation with an IVF specialist about elective egg-freezing. Existing information was the Victorian Assisted Reproductive Treatment Authority website. Online surveys were completed at recruitment (baseline), 6, and 12-months. Participants/materials, setting, methods Australian women aged ≥18 years, considering elective egg-freezing, proficient in English, and with internet access were recruited using various methods including social media, Google advertising, newsletters, and clinic referrals. Participants completing the baseline survey were randomised (intervention n = 150, control n = 156) and emailed their allocated resources. Subsequent surveys were emailed 6 and 12-months post-randomisation. Surveys covered decisional conflict (primary outcome), distress, egg-freezing and fertility knowledge, decision made/not made, preparedness for decision-making, informed choice, and decisional regret. Main results and the role of chance Of 306 participants (mean age=30 years, SD: 5.2), 50% were single and 65% worked in professional occupations. At 6-months, the intervention group was substantially more prepared for decision-making than the control (Preparation for Decision-Making Scale; mean score difference: 9.22 [95% CI: 2.35, 16.08], p = 0.009). Overall, 77% of participants completed the primary outcome at 12-months (intervention n = 113, control n = 124). Between baseline and 12-months, the mean reduction in Decisional Conflict Scale (DCS) scores was greater for the intervention group than the control (mean score difference: -6.99 [95% CI: -12.96, -1.02], p = 0.022), whilst there were no group differences in distress (Depression Anxiety and Stress Scale; mean score difference: 0.61 [95% CI: -3.72, 4.93], p = 0.783), knowledge (study-specific scale; mean score difference: 0.23 [95% CI: -0.21, 0.66], p = 0.309) and whether a decision had been made about egg-freezing (odds ratio: 1.95 (95% CI: 0.67, 5.69), p = 0.221). No differences were observed between groups in informed choice (Multi-Dimensional Measure of Informed Choice; relative risk: 1.00 [95% CI: 0.81, 1.25]) or decision regret (Decisional Regret Scale; median score difference: -5.00 [95% CI: -15.30, 5.30]) for participants who had made their decision about egg-freezing at 12-months (intervention n = 48, control n = 45). Limitations, reasons for caution The total eligible population reached cannot be calculated due to the broad recruitment methods used. Adaption of some scales to improve relevancy may impact validity. Biases from self-selection and the use of self-reported data are possible, and some results had small sample sizes limiting the inferences made. Wider implications of the findings This is the first study to evaluate the effectiveness of a Decision-Aid for women considering elective egg-freezing. It demonstrates the benefit of a Decision-Aid in supporting women’s decision-making. Given these results, the Decision-Aid will be made publicly available. There is also potential to adapt the tool for international relevancy. Trial registration number ACTRN12620001032943

Scientific yoga module for hypothyroidism: A study protocol for tele-yoga RCT

BackgroundManagement of thyroid dysfunction has a direct effect on the quality of life and studies have recognized that hypothyroidism has become a public health challenge. Although conventional medicine is widely used, its long-term side effects are elucidated. This study aims to conduct a randomized controlled trial (RCT) through tele-mode to assess the effectiveness of the newly developed and validated “Scientific Yoga Module” as a telehealth concept for improving the quality of life in patients with hypothyroidism along with management of other symptoms as compared to the standard of care. MethodThis is a single-blinded, two-arm, parallel-group RCT in which at least a total of 120 primary hypothyroid subjects both male and female between the age group 18 to 60 will be recruited from the database of Swami Vivekananda Yoga Anusandhana Samsthana (SVYASA). Participants will be randomly divided into a yoga intervention group (n = 60) and a waitlist control group (n = 60) as per the inclusion and exclusion criteria of the study. A tele-yoga intervention for six months will be administered and pre-interim-post data will be recorded for both groups. This protocol is designed to study the effect of Scientific Yoga Module intervention on primary assessments of SF-36 scale [health-related quality of life (HRQOL) that includes physical, mental, emotional, and social states] along with secondary assessments on the biochemical test of thyroid profile-{Triiodothyronine (T3), Thyroxine (T4), Thyroid Stimulating Hormones (TSH)}, Body Mass Index (BMI), Blood Pressure (BP), Fatigue Assessment Scale (FAS), Perceived Stress Scale (PSS), Gita Inventory of personality scale (GIP). ConclusionTo the best of our knowledge, this tele-yoga RCT for hypothyroidism will be the first clinical trial to analyze the effectiveness of a “Scientific Yoga Module” imparted through tele-mode.

Critical Care Cycling to Improve Lower Extremity Strength (CYCLE): protocol for an international, multicentre randomised clinical trial of early in-bed cycling for mechanically ventilated patients

IntroductionIn-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot...

Physical activity and exercise capacity as composite versus single categorical endpoints for trials of exercise-based cardiac rehabilitation interventions: comparison of sample size requirements

Abstract Funding Acknowledgements Type of funding sources: None. Introduction A composite primary endpoint consists of two or more component endpoints, events or outcomes. If any one of these is observed, it is considered that the composite primary endpoint has been reached. A potential advantage of a composite over a single primary endpoint in a randomised controlled trial (RCT) is a reduction of the required sample size. Purpose The combined endpoint "major adverse cardiac events" (MACE) is well-established in cardiovascular research, but MACE is often unsuitable in trials of exercise-based cardiac rehabilitation interventions with short follow-up periods. We therefore explored the application of a composite primary endpoint incorporating exercise capacity and physical activity for parallel-group RCTs of exercise-based cardiac rehabilitation (CR) interventions. Methods Our composite endpoint combines two categorical (binary) single endpoints, i.e., exercise capacity (given as maximum mechanical power output of a graded exercise test) and physical activity. Thresholds for categorisation were defined on literature-based minimal clinically worthwhile changes and defined as an increase of 15 W or more for improving exercise capacity and an increase of 10 min/day or more for improving moderate to vigorous physical activity (MVPA). If the aim of an intervention is to avoid clinically meaningful deterioration (i.e., to achieve maintenance as opposed to improvement), the threshold is defined as deterioration in exercise capacity of less than 15 W and a reduction in MVPA of less than 10 min/day (figure 1). To illustrate the impact of a single versus a composite primary end point on sample size requirements, we used real-world data from two completed phase 3 CR trials ([1] and [2]). We applied the commonly used formula for estimating sample sizes to detect the difference between the probabilities of an event in two independent groups [3]. Results Sample size requirements for detecting a between-group difference of 5%, 10%, 15% and 20% under the different endpoint approaches are shown in table 1. If the aim of the intervention is to achieve improvement, the composite endpoint results in approximately equivalent sample size requirements to the single endpoint. If the aim of the intervention is to achieve maintenance, the composite endpoint results in markedly lower sample size requirements compared to the primary endpoint. Statistically, these differences are driven by the percentage of improvers or maintainers in the control group of the reference population. Conclusion The composite primary endpoint approach can be a useful alternative to the single primary endpoint in trials of exercise-based CR. Depending on the baseline probability, it may be possible to reduce the sample size requirement by applying a composite endpoint. In our examples, the composite endpoint results in smaller sample size requirements when the intervention aim is to avoid clinically meaningful deterioration.

Mobile-assisted medication adherence support intervention among tuberculosis patients: a parallel group randomized control trial

Mobile-assisted medication adherence support intervention among tuberculosis patients: a parallel group randomized control trial

A structured, telephone-delivered intervention to reduce methamphetamine use: study protocol for a parallel-group randomised controlled trial

BackgroundAustralia has one of the highest rates of methamphetamine (MA) use in the world; however, uptake of in-person psychological treatment remains extremely low due to numerous individual (e.g. stigma, shame) and structural (e.g. service accessibility, geographical location) barriers to accessing care. Telephone-delivered interventions are ideally placed to overcome many of the known barriers to treatment access and delivery. This randomised controlled trial (RCT) will examine the efficacy of a standalone, structured telephone-delivered intervention to reduce MA problem severity and related harms.MethodsThis study is a double-blind, parallel-group RCT. We will recruit 196 ± 8 individuals with mild to moderate MA use disorder from across Australia. After eligibility and baseline assessments, participants will be randomly allocated to receive either the Ready2Change-Methamphetamine (R2C-M) intervention (n = 98 ± 4; four to six telephone-delivered intervention sessions, R2C-M workbooks and MA information booklet) or control (n = 98 ± 4; four to six ≤5-min telephone check-ins and MA information booklet including information on accessing further support). Telephone follow-up assessments will occur at 6 weeks and 3, 6 and 12 months post-randomisation. The primary outcome is change in MA problem severity (Drug Use Disorders Identification Test, DUDIT) at 3 months post-randomisation. Secondary outcomes are as follows: MA problem severity (DUDIT) at 6 and 12 months post-randomisation, amount of methamphetamine used, methamphetamine use days, methamphetamine use disorder criteria met, cravings, psychological functioning, psychotic-like experiences, quality of life and other drug use days (at some or all timepoints of 6 weeks and 3, 6 and 12 months post-randomisation). Mixed-methods program evaluation will be performed and cost-effectiveness will be examined.DiscussionThis study will be the first RCT internationally to assess the efficacy of a telephone-delivered intervention for MA use disorder and related harms. The proposed intervention is expected to provide an effective, low-cost, scalable treatment for individuals otherwise unlikely to seek care, preventing future harms and reducing health service and community costs.Trial registrationClinicalTrials.gov NCT04713124. Pre-registered on 19 January 2021.

Impact of hypothermia alert device (BEMPU) on improvement of duration of Kangaroo Mother Care (KMC) provided at home: parallel-group randomized control trial

The objective of the study was to determine if using the hypothermia-detecting bracelet (named BEMPU) improves the duration of Kangaroo Mother Care (KMC) at home by one hour. This parallel-group randomized controlled trial was conducted at a step-down nursery of a teaching hospital. Neonates between 1000 and 2000 g were randomized to BEMPU and control groups at the time of discharge. BEMPU was applied at the wrist of each newborn in the BEMPU (intervention) group. Parents were advised to keep the BEMPU in place till 4 weeks post-discharge. The BEMPU generates a beep sound as an alarm when a newborn's temperature drops below 36.5 °C. Parents in both groups were trained to provide KMC at home. Parents in the BEMPU group received the "KMC chart" and "BEMPU beep chart," while the control group received the "KMC chart" only. In the "KMC chart," parents entered information about KMC hours on a real-time basis, and in the "BEMPU beep chart," they entered information about alarm beeps from BEMPU on a real-time basis till 4 weeks post-discharge. Independent samples t-test was used to compare mean KMC hours between the two groups. A total of 128 neonates participated in the study (64 in BEMPU and 64 in Control groups). The mean(SD) gestational age for the BEMPU group was 34.04(2.84) weeks vs 34.75(2.70) weeks for the control group. In BEMPU group, mean(SD) daily time spent doing KMC was significantly higher in 1st week [4.78(2.93) vs. 3.22(2.44) h, p = 0.003], in 2nd week [4.52(3.43) vs. 2.84(2.95) h, p = 0.008], in 3rd week [4.23(3.71) vs. 2.30(2.70) h, p = 0.003], in 4th week [3.72(3.30) vs. 1.95(2.65) h, p = 0.003] as compared to control group. BEMPU improved the daily duration of KMC hours at home compared to the control group over four weeks. Clinical Trial Registration: This trial is registered at Clinical Trials Registry India with registration number: CTRI/2018/08/015154 and accessible at http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=27600&EncHid=&modid=&compid=%27,%2727600det%27 Registered on 01/08/2018.

Primary results of a phase-III, randomized controlled trial of the Behavioral Intervention for increasing Physical Activity in Multiple Sclerosis project

Background We undertook a phase-III, randomized controlled trial (RCT) that examined the effectiveness of a behavioral intervention based on social cognitive theory (SCT) and delivered through the Internet using e-learning approaches for immediate and sustained increases in physical activity among persons with multiple sclerosis (MS). Method The study followed a parallel group RCT design. Persons with MS (N = 318) were randomized into either behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions. The conditions were administered over a 6-month period by persons who were uninvolved in screening, recruitment, random assignment, and outcome assessment. There was a 6-month follow-up period without access of conditions. We collected outcome data every 6 months over the 12-month period. The primary outcome was device-measured minutes/day of moderate-to-vigorous physical activity (MVPA). The data analysis involved a modified intent-to-treat approach (i.e. those who received the allocated conditions) using a linear mixed model. Results There was a significant group by time interaction on the primary outcome of device-measured minutes/day of MVPA (p < 0.005). MVPA was increased immediately after the 6-month period in the behavioral intervention compared with control, and this difference was sustained over the 6-month follow-up. Conclusion This study provides evidence for the effectiveness of a widely scalable approach for increasing MVPA in persons with MS.

P445 Network meta-analysis to evaluate the comparative efficacy of intravenous and subcutaneous infliximab and vedolizumab in the maintenance treatment of adult patients with Crohn’s Disease and Ulcerative Colitis

Abstract Background Network meta-analysis (NMA) using randomised controlled trial (RCT) data can provide indirect evidence on comparative efficacy of various treatments.1 The NMA reported herein was conducted to evaluate infliximab (IFX) and vedolizumab (VDZ) comparative efficacy during maintenance treatment of moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC), covering various dosing regimens and administration routes for each biologic. Methods Studies were identified by literature searches that included publications up to 1 November 2022. Parallel-group RCTs evaluating IFX or VDZ (intravenous [IV] or subcutaneous [SC]) for maintenance treatment of adult patients with moderate-to-severe CD or UC that reported clinical remission rates were included. Eligible studies treated patients for a minimum of 22 weeks, with follow-up of 30–60 weeks for maintenance. Clinical remission rates in tumour necrosis factor inhibitor (TNFi)-naïve patients from each study were analysed in a Bayesian NMA fixed-effect model. Results Overall, 13 RCTs were identified and included in the analysis (Table 1 for CD and Table 2 for UC). The difference in study design between IFX (treat-through) and VDZ (re-randomisation of induction responders only) was noted. A connected network of evidence could be generated using CD and UC studies (Figures 1A and 1B, respectively). In both CD and UC, IFX SC 120 mg had the highest odds ratio (95% confidence interval [CI]) vs. placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90–18.2]; UC: 5.45 [1.94–15.3]), albeit with the CIs overlapping with the CIs of the other tested regimens (Figures 2A and 2B). In both CD and UC, IFX SC 120 mg ranked highest for clinical remission among the biological agents, dosing regimens, and routes of administration tested. Conclusion In both CD and UC, IFX SC showed a favourable efficacy profile for achieving clinical remission during maintenance treatment of TNFi-naïve adult patients, when compared with the other IFX IV or VDZ IV/SC regimens tested.