Open-label Randomized Control Trial Research Articles

RTID-03. A MULTICENTER, RANDOMIZED, CONTROLLED TRIAL OF FOCUSED-ULTRASOUND-MEDIATED BLOOD-BRAIN BARRIER DISRUPTION PLUS SYSTEMIC PEMBROLIZUMAB FOR PATIENTS WITH NSCLC BRAIN METASTASES (LIMITLESS)

Abstract BACKGROUND Systemic therapy for brain metastases (BM) is hindered by blood-brain barrier (BBB). Low-intensity focused ultrasound (LIFU), combined with IV microbubble oscillators, leads to non-invasive BBB disruption, which could enhance intracranial delivery of systemic immune checkpoint inhibitors. This randomized controlled trial (RCT) aims to evaluate safety and efficacy of LIFU-mediated BBB disruption plus systemic pembrolizumab for NSCLC BM. METHODS LIMITLESS (NCT05317858) is an ongoing, multicenter, parallel-arm, open-label RCT that randomizes NSCLC BM patients on standard-of-care pembrolizumab monotherapy to LIFU plus pembrolizumab (arm 1) or pembrolizumab alone (arm 2) in a 2:1 ratio. Included patients have age ≥18 years, normal organ function, KPS ≥70, EGFR- and ALK-negative primary tumor, and ≤3 BM with ≥1 BM meeting RANO-BM measurable disease criteria. All patients receive standard-of-care therapy, while those on arm 1 undergo LIFU before each pembrolizumab dose (200mg IV q3weeks). Patients undergo pre-treatment brain MRI, followed by IV microbubbles for enhanced sonication effects. MR-guided BBB disruption is performed using transcranial 220kHz LIFU device with real-time acoustic-feedback-based power control for maintaining effective microbubble activation. Pembrolizumab is infused immediately after sonication, and repeat MRI is done 24-48 hours later to assess treatment effects. Primary study outcome is overall objective response rate (ORR) at 6 months as assessed using RANO-BM. Using Bayesian design for power analysis, a superior ORR of 60% is assumed for LIFU arm versus 30% for control arm for total sample size of N=96 (64 participants in LIFU and 32 in control arm), for 80% power using two-sided chi-square test with alpha=0.05. For upper-bound estimate, ORR of 45% in LIFU arm and 30% in control arm, the study needs N=369 participants (246 in LIFU arm and 123 in control arm). Secondary outcomes are best ORR and median time-to-response. Exploratory outcomes are median progression-free survival (PFS), overall survival (OS), median intracranial PFS, median extracranial PFS, and quality of life. Patient enrollment commenced in 2022 and remains ongoing.

Comparison of Letrozole Versus Combination Letrozole and Clomiphene Citrate (CC) for Ovulation Induction in Sub Fertile Women with Polycystic Ovarian Syndrome (PCOS)-An Open Label Randomized Control Trial.

To evaluate the effectiveness of Letrozole and Clomiphene (CC) combination versus Letrozole alone for ovulation induction in infertile women with PCOS. This was an open label randomized controlled trial conducted between September 2020 and March 2023 at a tertiary level hospital. Women with a diagnosis of infertility and PCOS were included. Participants were randomized in a 1:1 ratio, to either the combination of 2.5mg letrozole and 50mg Clomiphene Citrate (CC) daily or 2.5mg letrozole alone from 2nd to 6thday of menstrual cycle for up to three treatment cycles. The primary outcome was ovulation rate per cycle. The secondary outcomes included ovulation rate per woman randomised, cumulative pregnancy and live birth rates. A total of the 120 participants, 59 women in Letrozole and CC arm (intervention) and 61 women in the Letrozole alone arm (control) were recruited. The woman per cycle ovulation rate following Letrozole and CC combination versus Letrozole alone (71/92 (77.2%) vs. 52/83 (62.6%), RR 1.43, 95%CI 0.99 to 2.06) but was not statistically significant. A per ITT analysis, the clinical pregnancy rate per woman randomized (16/61(26.2%) vs. 13/59(22%), RR 1.12, 95%CI 0.76 to 1.64) and live birth rate per woman randomized (10/61(16.4%) vs 11/59(18.6%), RR 0.92, 095%CI 0.57 to 1.50) did not differ significantly between Letrozole and CC versus Letrozole group. There was no significant improvement in ovulation, clinical pregnancy, or live birth rates with a combination of letrozole and CC versus letrozole alone in per woman randomized with PCOS. Trial RegistrationThe trial was prospectively registered in the clinical trial registry of India (CTRI registration number CTRI/2020/07/026263), Registration dated: February 26, 2020.

Mosquitocidal efficacy and pharmacokinetics of single-dose ivermectin versus three-day dose regimen for malaria vector control compared with albendazole and no treatment: An open-label randomized controlled trial

ObjectivesWhen malaria vectors consume ivermectin in a blood meal, their survival probability decreases, potentially reducing malaria transmission during mass drug administrations. However, questions remain regarding the optimal dosing. This study aimed to compare the mosquitocidal effect and pharmacokinetics of two-dose regimens of ivermectin for malaria vector control. DesignWe conducted an open-label randomized control trial in Kenya, staggered in blocks with sequential intervention groups and parallel controls. Participants were randomly assigned (2:1:1:1) using computer random-sequence generation, unstratified, with one block of six pharmacokinetics-only participants (single-dose ivermectin) and six blocks of four participants (3:1 intervention vs control), to receive single-dose ivermectin (400 mcg/kg, n = 12), three daily doses (3-day regimen 300 mcg/kg, n = 6), albendazole (400 mg, n = 6), or no treatment (negative control, n = 6). Our primary outcome was Anopheles gambiae survival (time-to-event [days]) after blood feeding up to 10 days after drug administration. We also evaluated pharmacokinetics (peak plasma and capillary blood concentration, areas under the plasma and capillary blood concentration-time curve from time of last administration to time of last observation, time to reach peak plasma and capillary blood concentration, terminal elimination half-life) up to 7 days after treatment. ResultsA total of 36 healthy volunteers aged 21-32 years were recruited into the study and followed up to completion, with two participants not attending the visit on day 28. All drug regimens were well-tolerated. Both regimens showed significant mosquitocidal effect in the first 7 days. At 10 days after treatment, the single dose presented superior longevity of effect (adjusted hazard ratio = 3.91; 95% confidence interval = 1.93-7.93; P <0.001) compared with the triple dose (adjusted hazard ratio = 1.79; 95% confidence interval = 0.88-3.62; P = 0.0.11). Albendazole had, overall, no mosquitocidal effect. ConclusionsIt is unclear why a single dose led to increased bio-efficacy compared with a triple dose. We recommend trials investigating ivermectin mass drug administrations for malaria control to consider single-dose ivermectin. A single-dose regimen is also expected to present additional operational advantages compared with a 3-day regimen, leading to improved programmatic suitability.

Supervised Disulfiram Should Be Considered First-line Treatment for Alcohol Use Disorder.

Despite the prevalence of alcohol use disorder (AUD) in the United States, the armamentarium of FDA-approved medications available for AUD treatment is remarkably small. Disulfiram, 1 of only 3 approved medications, is consistently designated as a second-line option in national treatment guidelines, citing inconsistent evidence, lack of patient preference, and safety concerns. These concerns, however, stem from a misguided interpretation of the evidence that exclusively relies upon double-blind randomized controlled trials (RCT). When viewed instead as both a medication and a behavioral intervention, open-label RCTs become a more appropriate research method, yielding overwhelmingly favorable efficacy data for disulfiram, and supervised disulfiram, in particular. With these data in mind, supervised disulfiram should be redesignated as a first-line intervention in both treatment guideline creation and clinical pathway tools. The addiction medicine community can no longer afford to neglect this critical therapeutic resource.

Breastfeeding Success With Use of Electric Breast Pump Versus Inverted Syringe Technique in Lactating Women With Inverted Nipple: Open Labelled Randomized Control Trial.

Background Inverted nipple is a commonly encountered impediment to proper attachment and latch establishment. Correction of inversion using a disposable syringe represents the conventional method of management. However, it is understudied, cumbersome, and inconvenient. Using electric breast pump represents a more physiological method to achieve correction of inversion. This open-label, randomized control trial investigated syringing versus electric breast pump both in terms of effectiveness in achieving correction of inversion of nipple and patient satisfaction with the use of the assigned intervention. Objectives The primary objective of this study was to compare breastfeeding success by Day 3 postnatal age (achieving correction of inversion of nipple and establishment of direct breastfeeding) in syringing versus electric breast pump in mothers with inverted or flat nipples. The secondary objective was to compare the two methods for the pain experienced by the mother while using syringing versus an electric breast pump. Methodology/Design This was a single-center, open-label randomized control trial performed at a tertiary care neonatal unit in Eastern India, from December 2022 to September 2023. 60 healthy mothers with inverted nipples were randomly allocated to one of two interventions: Group A (n=30, syringing); or Group B (n=30, electric breast pump). Both groups were compared for the establishment of breastfeeding by Day 3 postnatal age and daily maximum pain scores till Day 3 (visual analogue scale). Multivariable logistic regression was used to look for factors independently associated with establishment of breast feeding by Day 3 postnatal period. Chi square test was used to compare the proportions of different outcomes between the groups. Results The primary outcome of establishment of breastfeeding by Day 3 postnatal period was achieved in 18 (60%) mothers in syringe group vs. 17 (56.67%) in the breast pump group, with no statistically significant difference (p=0.793). In the first two days the pain score differences were not statistically significant, but on Day 3, 28 (93.99%) mothers in the electric breast pump group had no/mild pain compared to 22 (73.33%) mothers in the syringe usage group. This difference was statistically significant (p= 0.038). Conclusion In hospital settings where electric breast pump is easily available, the same may be preferred over inverted syringe technique for achieving establishment of breastfeeding by Day 3 postnatal period with minimal nipple pain in mothers. However, further large scale studies will be required to confirm these findings.

Does smoking cessation reduce other substance use, psychiatric symptoms, and pain symptoms? Results from an emulated hypothetical randomized trial of US veterans.

Quitting smoking may lead to improvement in substance use, psychiatric symptoms, and pain, especially among high-risk populations who are more likely to experience comorbid conditions. However, causal inferences regarding smoking cessation and its subsequent benefits have been limited. We emulated a hypothetical open-label randomized control trial of smoking cessation using longitudinal observational data of HIV-positive and HIV-negative US veterans from 2003-2015 in the Veterans Aging Cohort Study. We followed individuals from the first time they self-reported current cigarette smoking (baseline). We categorized participants as quitters or non-quitters at the first follow-up visit (approximately 1 year after baseline). Using inverse probability weighting to adjust for confounding and selection bias, we estimated odds ratios for improvement of co-occurring conditions (unhealthy alcohol use, cannabis use, illicit opioid use, cocaine use, depressive symptoms, anxiety symptoms, and pain symptoms) at second follow-up (approximately 2 years after baseline) for those who quit smoking compared to those who did not, among individuals who had the condition at baseline. Of 4,165 eligible individuals (i.e., current smokers at baseline), 419 reported no current smoking and 2,330 reported current smoking at the first follow-up. Adjusted odds ratios (95% confidence intervals) for associations between quitting smoking and improvement of each condition at second follow-up were: 2.10 (1.01, 4.35) for unhealthy alcohol use, 1.75 (1.00, 3.06) for cannabis use, 1.10 (0.58, 2.08) for illicit opioid use, and 2.25 (1.20, 4.24) for cocaine use, 0.78 (0.44, 1.38) for depressive symptoms, 0.93 (0.58, 1.49) for anxiety symptoms, and 1.31 (0.84, 2.06) for pain symptoms. While a causal interpretation of our findings may not be warranted, we found evidence for decreased substance use among veterans who quit cigarette smoking but none for the resolution of psychiatric conditions or pain symptoms. Findings suggest the need for additional resources combined with smoking cessation to reduce psychiatric and pain symptoms for high-risk populations.

Quality-of-life outcomes of the ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial.

To comprehensively compare quality-of-life (QoL) outcomes between open partial nephrectomy (OPN) and robot-assisted PN (RAPN) from the randomised ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial, as QoL data comparing OPN and RAPN are virtually non-existent, especially not from randomised controlled trials (RCTs). The ROBOCOP II was a single-centre, open-label RCT between OPN and RAPN. The pre-planned analyses of QoL outcomes are presented. Data were analysed descriptively in a modified intention-to-treat population. A total of 50 patients underwent surgery. At postoperative Day 90 (POD90), there was no significant difference for the Kidney Disease Quality of Life-Short Form questionnaire score (mean [sd] OPN 72 [20] vs RAPN 76 [15], P = 0.850), while there were advantages for RAPN in the subdomains of 'Pain' (P = 0.006) and 'Physical functioning' (P = 0.011) immediately after surgery. For the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core there were overall advantages directly after surgery (mean [sd] score OPN 63 [20] vs RAPN 75 [17], P = 0.031), as well as for the subdomains 'Fatigue' (P = 0.026), 'Pain' (P = 0.002) and 'Constipation' (P = 0.045) but no differences at POD90. There were no differences for the EuroQoL five Dimensions five Levels questionnaire at POD90 (mean [sd] score OPN 70 [22] vs RAPN 72 [17], P = 1.0) or at any other time point. Finally, no significant differences were found for the overall Convalescence and Recovery Evaluation questionnaire score at POD90 (mean [sd] OPN 84 [13] vs RAPN 86 [10], P = 0.818) but less pain in the RAPN group (P = 0.017) directly after surgery. Pain and physical functioning as subdomains of QoL are improved after RAPN compared to OPN in the early postoperative course, while there are no differences anymore after 3 months.

Randomized controlled trial of digital therapeutics for temporomandibular disorder: A pilot study

ObjectivesTemporomandibular disorder (TMD) is a common condition that affects the temporomandibular joint (TMJ) and the muscles of the jaw, resulting in pain and dysfunction. TMD is affected by both behavioral and psychological factors. Digital therapeutics (DTx) can exert therapeutic effects by controlling behavioral factors through the delivery of appropriate interventions. Here, we report an open-label randomized control trial to evaluate the efficacy of DTx for TMD. MethodsWe recruited 40 participants diagnosed with TMD. Participants were randomly divided into an intervention group (DTx use, n = 20) and a control group (n = 20). The intervention group received the usual treatment process for TMD in addition to the use of the DTx. The control group received the usual treatments only. Patients in both groups were followed up for 3–4 weeks, and outcome data were collected and analyzed. ResultThe intervention group showed a significant reduction in pain scores as measured by the numerical rating scale (NRS) (p = 0.016). Additionally, the intervention group showed a statistically significant increase in maximal mouth opening compared to the control group (p = 0.0079). However, there were no significant differences in improvement in the Jaw Functional Limitation Scale, Oral Behavior Checklist, and Patient Health Questionnaire-4 between the two groups (p = 0503, = 0.820, and = 0.943, respectively). ConclusionThis RCT reveals DTx potential in TMD, showing pain and mouth opening improvements with conventional treatment. But no significant changes were noted in other outcomes. The findings advocate for more extensive, long-term research to solidify DTx's role in TMD management. Clinical significanceThis research underlines DTx potential to improve pain outcomes in TMD therapy, reinforcing its value as a complementary treatment modality.

Weight gain in infants with congenital heart disease; breastfeeding alone versus supplemental spoon-feeding of expressed breast milk: an open-label, pilot, randomised control trial.

Infants with congenital heart disease and increased pulmonary blood flow frequently suffer from feeding difficulties and growth failure. Providing expressed breast milk by spoon has been hypothesised to decrease energy expenditure in these infants as compared to breastfeeding. This study assessed the effect of supplemental feeding of expressed breast milk on weight gain in infants with unoperated congenital heart disease. This was a prospective open-label randomised control trial. In total, 50 infants with post tricuspid left to right shunt were enrolled in the study. In the intervention group, apart from breastfeeding, a minimum predetermined volume of expressed breast milk was targeted to be given by spoon. 30-50 kcal/kg/day was given by expressed breast milk by spoon-feeding. In the control group, the infants were given at least 8 feeds per 24 hours by direct breastfeeding. Both groups were followed up for 1 month and assessed for weight gain. Despite a high rate of protocol breach in both groups (30% overall), infants in the intervention group had better weight gain at one-month follow-up compared to those in the control group, 780 ± 300 versus 530 ± 250 gm (p = 0.01). In infants with left to right shunts, supplemental feeding of expressed breast milk by spoon along with breastfeeding resulted in significantly higher average weight gain at 30 days compared to the control group who received breastfeeding alone. Future studies with larger sample sizes and longer follow-ups need to be done to confirm the findings of this study.

Study protocol for supplementation of single high dose Vitamin D in deficient critically ill children and assessment of their short-term outcome: An open label randomized control trial

Vitamin D, traditionally linked to bone metabolism, plays pleotropic roles in cellular regulation. In critically ill children, Vitamin D deficiency is associated with adverse outcomes, motivating our open-label Randomized Control Trial. Our aim is to assess short-term outcomes in Vitamin D-deficient critically ill children following a single high oral dose. Conducted at a central Indian tertiary care hospital with a sample size of 100, participants aged 1 month to 18 years will be randomized. Group A receives standard treatment with customary cholecalciferol dosing, while Group B receives standard treatment with a single high oral/nasogastric tube dose (10,000 IU/kg to 400,000 IU) of Vitamin D. Outcomes include PICU stay duration, mechanical ventilation period, occurrences of Ventilator-Associated Pneumonia and Central Line-Associated Blood Stream Infection, instances of Acute Kidney Injury, presence of Multiorgan dysfunction, maximum Vasoactive-Inotrope Score, and mortality rates. Results and interpretation will be guided by study observations. Trial registration: CTRI/2022/10/046556.

Protocol for a prospective, multicenter, parallel-group, open-label randomized controlled trial comparing standard care with Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control: the CO-PILOT trial

PurposeAdvanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA1c has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group.MethodsA prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7–25 years with T1D, a current HbA1c ≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA1c between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes.ConclusionThis study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden.Trial registrationThis trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452).

Feasibility of using WHO's e-mhGAP-IG Mobile Application for Child and Adolescent Mental/Behavioral Disorders and Substance Use in Indian Setting: Protocol paper

Background: The treatment gap for people with common mental disorders is large, estimated to be 75–95% in India; the reasons are multi-factorial. It was found that 89% of the primary health centers are not providing mental health care services. Technology like the electronic-mental Health Global Action Program-Intervention Guide (e-mhGAP-IG) is necessary to fill this gap, which in turn helps to attain one of the aims of National Mental Health Program-1982. Hence, the study is planned to understand the feasibility and adaptability of WHO’s e-mhGAP-IG by the primary health workers in the delivery of mental health care for child and adolescent mental/behavioral disorders (CMH) and substance use disorders (SUB). Methods: It is an open-label randomized control trial planned to conduct at primary healthcare centers, Chittoor district. Primary health care staff working at PHCs/Sub-centers having one year experience, and being able to handle smart phones will be included in the study. Data will be collected using a self-structured case report form (CRF) and analyzed by applying per protocol analysis using JAMOVI software. The cost of intervention and the impact on disease outcomes will be taken concurrently to estimate the cost-effectiveness of the intervention. Trial registration: CTRI/2023/04/051899 dated 24/04/2023 under the clinical trials registry-India Protocol version: 1.0 dated 24/04/2023

Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial)

BackgroundEndoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate.MethodsThis is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study.DiscussionThis is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors.Trial registrationJapan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.

The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial.

Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that continuous positive airway pressure (CPAP) could have a favorable impact on these complications. We assessed the feasibility of conducting a randomized control trial in patients with type 2 diabetes and OSA over 2 years. We conducted an open-label multicenter feasibility randomized control trial of CPAP vs no CPAP in patients with type 2 diabetes and OSA. Patients with resting oxygen saturation < 90%, central apnea index > 15 events/h, or Epworth Sleepiness Scale ≥ 11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes. Eighty-three (40 CPAP vs 43 no CPAP) patients were randomly assigned, with a median (interquartile range) follow-up of 645 (545, 861) days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomly assigned to CPAP and several diabetes-related end points (chronic kidney disease, neuropathy, and quality of life). It was feasible to recruit, randomly assign, and achieve a high follow-up rate over 2 years in patients with OSA and type 2 diabetes. CPAP compliance might improve by a run-in period before randomization. A full randomized control trial is necessary to assess the observed favorable association between CPAP and chronic kidney disease , neuropathy, and quality of life in patients with type 2 diabetes. Registry: ISRCTN; Name: The impact of sleep disorders in patients with type 2 diabetes; URL: https://www.isrctn.com/ISRCTN12361838; Identifier: ISRCTN12361838. Makhdom EA, Maher A, Ottridge R, etal. The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial. J Clin Sleep Med. 2024;20(6):947-957.

High-dose versus low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised controlled trial

ObjectivesSympathetic crashing acute pulmonary edema (SCAPE) is a subset of heart failure with a dramatic presentation. The unique physiology of this condition requires a different management strategy from the conventional...

Efficacy and safety of insulin glargine 300 units/mL vs insulin degludec in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis.

Ultra-long-acting insulin analogs [insulin degludec (IDeg) and insulin glargine 300 units/mL (IGla-300)] offer a longer duration of action with less risk of hypoglycemia compared to other long-acting insulins. However, data about the comparative efficacy and safety are inconsistent. We searched CENTRAL, PubMed, Embase, ICTRP Search Portal, and ClinicalTrials.gov on 7 October 2022. Randomized controlled trials (RCTs) comparing the safety and efficacy of IDeg (100 or 200 units/mL) and IGla-300 in patients with type 1 or type 2 diabetes were included. Three review authors independently selected trials, assessed the risk of bias, extracted data, and evaluated the overall certainty of the evidence using GRADE. The primary outcomes were the change in glycated hemoglobin (HbA1c) and any hypoglycemia; the secondary outcomes were the change in fasting plasma glucose (FPG) and severe and nocturnal hypoglycemia. Four open-label RCTs were included (2727 participants), 3 parallel and 1 cross-over. Overall, the risk of bias assessment yielded some concern or high risk. There was a comparable change in HbA1c from baseline to the end of treatment, a mean difference of 0.07% (95% confidence interval (CI) 0.06 - 0.19; p = 0.29; 3 trials; 2652 patients; very low-certainty evidence), and a comparable rate of any hypoglycemia, rate ratio 1.02 (95% CI 0.8 - 1.3; p = 0.87; 3 trials; 2881 patients; very low-certainty evidence). IDeg resulted in more reduction in FPG compared to IGla-300, mean difference of 10.27 mg/dL (95% CI 7.25 - 13.29; p < 0.001; 3 trials; 2668 patients; low-certainty evidence). Similar rates of nocturnal and severe hypoglycemia were observed, rate ratio of 1.13 (95% CI 0.72 - 1.78; p = 0.54; 3 trials; 2668 patients; very low-certainty evidence) and 1.4 (95% CI 0.41 - 4.73; p = 0.59; 2 trials; 1952 patients; very low-certainty evidence), respectively. There is no evidence of a difference between IDeg and IGla-300 in the mean change in HbA1c and the risk of anytime, nocturnal, and severe hypoglycemia. IDeg appeared to cause a higher reduction in FPG compared to IGla-300. However, this finding should be interpreted with caution due to the small number of trials included and their high risk of bias. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364891, identifier CRD42022364891.

Does apneic oxygenation with nasopharyngeal cannula during intubation improve the oxygenation in patients with acute hypoxemic respiratory failure compared to the standard bag valve mask preoxygenation? An open-labeled randomized control trial.

In the context of acute hypoxemic respiratory failure (AHRF), ensuring effective preoxygenation and apneic oxygenation emerges as the pivotal approach ensuring for averting hypoxemic adverse events during endotracheal intubation. To investigate this, we conducted an open-label randomized controlled trial, aiming to assess the comparative effectiveness of nasopharyngeal high-flow oxygenation in conjunction with Bag-Valve-Mask (BVM) versus standard BVM preoxygenation in patients experiencing AHRF within the emergency department (ED). This prospective single-center, open-labeled, randomized controlled trial enrolled patients aged 18 years and above requiring rapid sequence intubation due to AHRF in the ED. Participants were randomly assigned in a 1:1 ratio to either the intervention arm (involving nasopharyngeal high-flow oxygenation and BVM preoxygenation) or the control arm (involving BVM preoxygenation alone). A total of 76 participants were enrolled in the study, evenly distributed with 38 individuals in each arm. Median (interquartile range [IQR]) SpO2 at 0 min postintubation was 95.5 (80%-99%) versus 89 (76%-98%); z-score: 1.081, P = 0.279 in the intervention and control arm, respectively. The most common postintubation complications included hypoxia (intervention arm: 56.7% vs. control arm: 66.7%) and circulatory/hypoxic arrest (intervention arm: 39.5% vs. control arm: 44.7%). There were no adverse complications in 36.7% (n = 11) of patients in the intervention arm. Despite the best possible medical management, almost half (52.6%) of patients in the intervention arm and 47.4% of patients in the control arm succumbed to their illnesses in the ED. The primary outcome revealed no statistically significant difference between the two arms. However, patients in the intervention arm exhibited fewer intubation-related adverse effects.

Rationale and design of the THIRST Alert feasibility study: a pragmatic, single-centre, parallel-group randomised controlled trial of an interruptive alert for oral fluid restriction in patients treated with intravenous furosemide

IntroductionAcute heart failure (HF) is a major cause of unplanned hospitalisation characterised by excess body water. A restriction in oral fluid intake is commonly imposed on patients as an adjunct...

Effects of participatory 'A'rt-Based Activity On 'Health' of Older Community-Dwellers: results from a randomized control trial of the Singapore A-Health Intervention.

The practice of participatory art has been found to support the promotion, prevention, and management of health across the lifespan. However, clinical trials investigating the benefits of creative activities curated with and conducted in museums among older adults in East Asia remains limited. The current research utilized a single-site, open-label randomized control trial (RCT) to evaluate a standardized Participatory 'A'rt-Based Activity On 'Health' of Older Community-Dwellers - the Singapore A-Health Intervention. Outcome measures include frailty as assessed by the Centre of Excellence on Longevity Self-administered Questionnaire, wellbeing as assessed by the Warwick-Edinburgh Mental Wellbeing Scales, and quality of life as assessed by the EuroQol-5D. 112 participants aged 60 and above were randomized into the intervention group (n = 56) or an inactive control group (n = 56). Participants completed four standardized online self-administered assessments at baseline, 5-week, 9-week and 12-week follow-up during the intervention period. Linear mixed model analyses revealed no statistically significant differences between the intervention group and control group for all outcome measures. However, within the intervention group, a consistent significant reduction in frailty was observed across time from baseline to 9 weeks (MD -0.44, 95% CI -0.85 to -0.039, p = 0.032), 5-weeks to 9-weeks (MD -0.64, 95% CI -1.03 to -0.24, p = 0.002), and 5-weeks to 12-weeks (MD -0.51, 95% CI -0.91 to -0.10, p = 0.014). Moreover, the post-test mean wellbeing score in the intervention group significantly improved over time at 9-weeks (MD 1.65, 95% CI 0.09 to 3.22, p = 0.039) and 12-week (MD 2.42, 95% CI 0.67 to 4.16, p = 0.006) as compared to baseline scores. The findings demonstrate the potential of a structured art and museum-based intervention as a resource for promoting health among aging populations. Such benefits transcend social, cultural, and societal contexts. ClinicalTrial.gov, NCT05945589.

Comparison of the therapeutic effects of 15 mg and 30 mg initial daily prednisolone doses in patients with subacute thyroiditis: a multicenter, randomized, open-label, parallel-controlled trial

Introduction Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We designed a randomized controlled trial (RCT) to compare the efficacy and safety of using a low initial dose of PSL with a standard initial dose of PSL in SAT patients. Patients and methods This open-label RCT was conducted at five hospitals in China from June 2019 to January 2022. SAT patients with moderate-to-severe pain or a poor response to non-steroidal anti-inflammatory drugs (NSAIDs) were randomly assigned in a 1:1 ratio to the experimental and control groups. The initial dose of PSL was 15 mg/d in the experimental group and 30 mg/d in the control group. The primary outcome was the total duration of PSL treatment, with non-inferiority prespecified with a margin of 7 days. Clinical trial registration number: ChiCTR1900023884. Results The full analysis set included 60 patients (30 in each group). The mean duration of PSL treatment in the experimental and control group was 34.62 ± 14.12 and 41.18 ± 16.89 days, respectively, meeting the non-inferiority criterion (pnon-inferiority = 0.0006). The total dose of PSL used in the experimental group was lower than in the control groups (330 vs 595 mg, p < 0.0001). There were no differences in the mean time to pain relief and complete resolution, the occurrence of recurrence, hypothyroidism, or adverse events between the groups. Conclusions The initial dose of 15 mg/d of PSL was not inferior to the dose of 30 mg/d in terms of efficacy and showed a similar safety profile. A low initial dose of PSL could be recommended for Chinese adult SAT patients who have a suboptimal response using NSAIDs or experience moderate-to-severe pain. KEY MESSAGES Low initial dose (15 mg/d) of prednisolone was non-inferior to the standard initial dose of prednisolone (30 mg/d) in treatment duration, time to pain relief, or the prevalence of hypothyroidism, recurrence, and adverse reactions in the treatment of subacute thyroiditis. Patients with subacute thyroiditis administered a low initial dose of prednisolone had a lower total dose of prednisolone compared to those receiving the standard dose of prednisolone.