Non-inferiority Randomized Controlled Trials Research Articles

Cost-effectiveness of single-day intravenous fosaprepitant versus three-day oral aprepitant anti-emetic regimen in pediatric patients receiving highly-emetogenic chemotherapy.

10075 Background: The non-inferiority of single-dose fosaprepitant to a three-day oral aprepitant-based anti-emetic regimen for pediatric patients receiving high emetogenic chemotherapy (HEC) has not been demonstrated. The cost-effectiveness of these regimens with respect to each other in India and the United States (US) is unknown. Methods: Individual patient data from an investigator-initiated, open-label, non-inferiority randomized control trial was used to estimate health states. The total costs and quality-adjusted life years (QALY) were calculated from the patient's perspective in India and the US. The incremental-cost utility ratio (ICUR) and net-monetary benefit (NMB) were calculated. One-way sensitivity analysis was done by varying the cost of medications, hospitalization and utility values by ±25%. Results: The fosaprepitant arm had a total QALY of 0.0116 compared to 0.0118 in the aprepitant arm. The use of fosaprepitant led to an incremental cost of $14.21 in India and a cost reduction of $193.81 in the US. The total cost of medication in the fosaprepitant arm was higher in India and lower in the US compared to the aprepitant arm. The cost of hospitalisation was lower in the fosaprepitant in both India and the US. The ICUR was -$59,974.86/QALY in India and $817,737.23/QALY in the US. The ICUR for India was located in the north-west quadrant of the cost-effectiveness plane, for the US it was located in the south-west quadrant below the willingness the pay threshold for the US. The ICUR estimate was most sensitive to the cost of fosaprepitant in India and the utility value of the complete protection health state in the US. Conclusions: Fosaprepitant was not found to be cost-effective versus aprepitant in India, comparatively it was cost-saving and cost-effective in the US. These findings highlight the necessity of region-specific considerations when evaluating the cost-effectiveness of anti-emetic regimens. [Table: see text]

Dye Chromoendoscopy Outperforms High-Definition White Light Endoscopy in Dysplasia Detection for Patients With Inflammatory Bowel Disease: An Updated Meta-Analysis of Randomized Controlled Trials.

Whether dye spray chromoendoscopy (DCE) adds value in surveillance colonoscopy with high-definition (HD) scopes remains controversial. This updated meta-analysis compares dysplasia detection using DCE and high-definition white light endoscopy (HD-WLE) in patients with inflammatory bowel disease (IBD) undergoing surveillance colonoscopy. A comprehensive search was performed for randomized controlled trials (RCT) comparing HD-WLE and DCE in patients with IBD. The primary outcome was to compare the proportion of patients with at least 1 dysplastic lesion detected by DCE vs HD-WLE. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using the random-effects model, with I2 > 60% indicating substantial heterogeneity. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence (CoE). Six RCT involving 978 patients were analyzed (DCE = 479 vs HD-WLE = 499 patients). DCE detected significantly more patients with dysplasia than HD-WLE (18.8% vs 9.4%), OR 1.94 (95% CI 1.21-3.11, I2 = 28%, P = 0.006, high CoE). This remained significant after excluding 2 RCT published as abstracts. A sensitivity analysis excluding a noninferiority RCT with a single experienced operator eliminated the results' heterogeneity, OR 2.46 (95% CI 1.56-3.90, I2 = 0%). Although high-grade dysplasia detection was numerically higher in the DCE group (2.8% vs 1.1%), the difference was statistically insignificant, OR 2.21 (95% CI 0.64-7.62, I2 = 0%, low CoE). Our updated meta-analysis supports DCE as a superior strategy in overall dysplasia detection in IBD, even with HD scopes. When expertise is available, DCE should be considered for surveillance colonoscopy in patients with high-risk IBD, with the acknowledgment that virtual chromoendoscopy shows equivalence in recent studies. Further multicenter trials with multiple endoscopists with varying expertise levels and longer-term outcome data showing a reduction in cancer or cancer-related death are needed.

Safety and care of no fasting prior to catheterization laboratory procedures: a non-inferiority randomized control trial protocol (SCOFF trial).

Cardiac catheterization procedures are typically performed with local anaesthetic and proceduralist guided sedation. Various fasting regimens are routinely implemented prior to these procedures, noting the absence of prospective evidence, aiming to reduce aspiration risk. However, there are additional risks from fasting including patient discomfort, intravascular volume depletion, stimulus for neuro-cardiogenic syncope, glycaemic outcomes, and unnecessary fasting for delayed/cancelled procedures. This is an investigator-initiated, multicentre, randomized trial with a prospective, open-label, blinded endpoint (PROBE) assessment based in New South Wales, Australia. Patients will be randomized 1:1 to fasting (6 h solid food and 2 h clear liquids) or to no fasting requirements. The primary outcome will be a composite of hypotension, hyperglycaemia, hypoglycaemia, and aspiration pneumonia. Secondary outcomes will include patient satisfaction, contrast-induced nephropathy, new intensive care admission, new non-invasive or invasive ventilation requirement post procedure, and 30-day mortality and readmission. This is a pragmatic and clinically relevant randomised trial designed to compare fasting verse no fasting prior to cardiac catheterisation procedures. Routine fasting may not reduce peri-procedural adverse events in this setting.

The Association between Acute and Late Genitourinary and Gastrointestinal Toxicities: An Analysis of the PACE B Study

Acute gastrointestinal (GI) and genitourinary (GU) toxicity after prostate radiotherapy (RT) has been shown to be associated with late toxicity with 3D conformal RT. However, whether this association is present with modern approaches, such as stereotactic body radiotherapy (SBRT), remains unclear. We analyzed patients treated within the international phase III non-inferiority randomized control trial, PACE-B, to assess the association between acute and late toxicity following SBRT and conventional/moderately hypofractionated radiotherapy (CRT). We hypothesize that acute toxicity is significantly associated with equivalent late toxicity following prostate SBRT and CRT. We analyzed patients with GI and GU Common Terminology Criteria for Adverse Events (CTCAE) measurements in the acute (≤12 weeks post-RT) and late period (6-24 months post-RT). Using logistic regression, we analyze the association between G2+ acute GI and GU toxicities with equivalent late toxicities. Lasso variable selection was used to determine patient, tumor and treatment variables to include in the multivariable model. The area under the receiver operator characteristics curve (AUC) was used to evaluate the model's predictive performance. Of patients included in this analysis (n = 842), 414 were treated with SBRT and 428 with CRT. In univariable analysis (UVA), G2+ acute GU toxicity was significantly associated with developing G2+ late GU toxicity after SBRT (OR 4.63, 95% CI (2.96-7.25), p<0.0001) and CRT (OR 2.83, 95% CI (1.69-4.71), p<0.0001). This association remained significant in multivariable analysis (MVA). The models AUC for predicting G2+ late GU toxicity after SBRT was 0.73 (95% CI, 0.67-0.78) and 0.66 (95% CI, 0.59-0.73) following CRT. In UVA, G2+ acute GI toxicity was associated with developing G2+ late GI toxicity after SBRT (OR 3.67, 95% CI (1.91-7.03), p <0.0001) and CRT (OR 4.4, 95% CI (2.04-9.47), p<0.0001). This association also remained significant in MVA. The models AUC for predicting G2+ late GI toxicity after SBRT was 0.66 (0.95% CI, 0.57-0.75) and 0.64 (95% CI, 0.57-0.72) following CRT. In UVA analysis, G2+ baseline GU symptoms were also associated with developing G2+ late GU toxicity after SBRT (OR 7.59, 95% CI (2.72-21.19, p<0.0001) and CRT (OR 7.98, 95% CI (3.03-20.96), p<0.0001), and this continued to be significant in MVA. Acute toxicity remained associated with persistent late toxicity (≥2 G2+ late events) and late toxicity 12-24 months. Our study demonstrates an independent association between acute and late GU/GI toxicity in patients treated with SBRT and CRT for localized prostate cancer. Recognizing those at risk of late toxicity can provide an opportunity for early intervention to improve outcomes. G2+ acute toxicity should be considered an essential variable for predicting late GI/GU toxicity after prostate RT.

Vonoprazan versus lansoprazole in erosive esophagitis - A systematic review and meta-analysis of randomized controlled trials.

Proton-pump inhibitors (PPIs) are the mainstay of treatment in erosive esophagitis (EE). An alternative to PPIs in EE is Vonoprazan, a potassium competitive acid blocker. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing vonoprazan to lansoprazole. Multiple databases searched through November 2022. Meta-analysis was performed to assess endoscopic healing at two, four and eight weeks, including for patients with severe EE (Los Angeles C/D). Serious adverse events (SAE) leading to drug discontinuation were assessed. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Four RCTs with 2208 patients were included in the final analysis. Vonoprazan 20mg once-daily was compared to lansoprazole 30mg once-daily dosing. Among all patients, at two and eight weeks post-treatment, vonoprazan resulted in significantly higher rates of endoscopic healing as compared to lansoprazole, risk ratios(RR) 1.1, p<0.001 and RR 1.04, p=0.03. The same effect was not observed at four weeks, RR 1.03 (CI 0.99-1.06, I2=0%) following therapy. Among patients with severe EE, vonoprazan resulted in higher rates of endoscopic healing at two weeks, RR 1.3 (1.2-1.4, I2=47%), p=<0.001, at four weeks, RR 1.2 (1.1-1.3, I2=36%), p=<0.001 and at eight weeks post-treatment, RR 1.1 (CI 1.03-1.3, I2=79%), p=0.009. We found no significant difference in the overall pooled rate of SAE and pooled rate of adverse events leading to drug discontinuation. Finally, the overall certainty of evidence for our main summary estimates was rated as high (grade A). Based on limited number of published non-inferiority RCTs, our analysis demonstrates that among patients with EE, vonoprazan 20mg once-daily dosing achieves comparable and in those with severe EE, higher endoscopic healing rates as compared to lansoprazole 30mg once-daily dosing. Both drugs have a comparable safety profile.

Preliminary examination of acceptability, feasibility, and effectiveness of internet-based cognitive behavioral therapy for treatment of depression and anxiety in infertile women

BackgroundDespite a large body of evidence supporting the effectiveness of internet-based cognitive behavior therapy (ICBT) for the treatment of depression and anxiety, there is no report of the efficacy of ICBT program in the Iranian population. The present study aimed to test the acceptability, feasibility, and effectiveness of ICBT program for the treatment of depression or anxiety in infertile women. MethodThis study consisted of two phases. In the first phase, we designed “Peaceful Mind”, an eight-session therapist-guided ICBT program. In the second phase, we tested the efficacy of the program by conducting 2-arm parallel group, non-inferiority randomized control trial, between October 2020 and July 2021.60 infertile women diagnosed with depression or anxiety disorders were divided randomly to ICBT treatment (n = 30) and face-to face CBT (n = 30). The participants received individual CBT sessions (60 min, over 8 weeks) and completed the questionnaires at the beginning, in mid-trial, and 8 weeks after the trial. The outcomes comprised Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI, Fertility problem inventory (FPI), Client Satisfaction Questionnaire (CSQ-8), and System usability scale (SUS). ResultsThe usability scores of the “Peaceful Mind” ICBT (M = 67.07, SD = 17.23, range = 1–100) and satisfaction with the treatment (M = 25.06, SD = 4.18, range = 1–32) were high. Patient adherence to the treatment in the ICBT group (86.6%) was the same as that in the CBT (73.3%). The between-group mean differences at the post-trial were −4.79 (CI 95% = −10.81 to 1.23) for depression scores and −4.15 (CI 95% = −9.52 to 1.22) for anxiety scores; both differences were within the non-inferiority margin points for the lower 95%CI. Conclusion“Peaceful mind” ICBT was found to be feasible and accessible for delivering the treatment to the patients. The study confirmed that both ICBT face-to face CBT were equally effective in reducing depression and anxiety of the patients.

Outcomes of the advanced visualization in corneal surgery evaluation trial; a non-inferiority randomized control trial to evaluate the use of intraoperative OCT during Descemet membrane endothelial keratoplasty

ObjectiveTo evaluate if an intraoperative-OCT (iOCT) optimized surgical protocol without prolonged overpressure is non-inferior to a standard protocol during Descemet membrane endothelial keratoplasty (DMEK).MethodsSixty-five pseudophakic eyes of 65 patients with Fuchs endothelial dystrophy scheduled for routine DMEK were recruited in this prospective non-inferiority international multicenter randomized control trial. Subjects were randomized to the control arm (n=33) without iOCT-use and raising the intraocular pressure above normal physiological limits for 8 minutes (i.e., overpressure) or the intervention arm (n=32) with OCT-guidance to assess graft orientation and adherence, while refraining from prolonged overpressure. The primary outcome was the incidence of postoperative surgery-related adverse events (AE). The non-inferiority margin was set at a risk difference of 10%. Secondary outcomes included iOCT-aided surgical decision making, surgical times, and endothelial cell density (ECD) corrected distance visual acuity (CDVA) at 6 months follow-up.ResultsIn the intervention group, 12 subjects developed 13 AEs compared to 13 AEs in 10 subjects in the control group (P=0.644). The risk difference measured -0.32% (95%CI: -10.29 – 9.84). The ECD and CDVA did not differ between the two groups 3 and 6 months postoperatively (P=&amp;gt;0.05). Surgeons reported that iOCT aided surgical decision-making in 40% of cases. Surgery and graft unfolding time were, respectively, 13% and 27% shorter in the iOCT-group.ConclusionsiOCT-guided DMEK surgery with refraining from prolonged over-pressuring was non-inferior compared to conventional treatment. Surgery times were reduced considerably and iOCT aided surgical decision-making in 40% of cases. Refraining from prolonged overpressure did not affect postoperative ECD or CDVA.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03763721 (NCT03763721).

Clinical evaluation of paraspinal mini-tubular technique vs. laminoplasty for spinal intradural extramedullary tumors: Study protocol for a multicenter, randomized controlled trial.

ChiCTR2100047582.

Comparison of rates of vaginal brachytherapy vs. external beam radiation post-hysterectomy for endometrial cancer patients in rural vs. urban settings (459)

<b>Objectives:</b> The GOG-99 trial published in 2004 demonstrated that patients with high-intermediate risk endometrial cancer benefit from adjuvant external beam radiation therapy (EBRT) post-hysterectomy to decrease the risk of recurrence. The PORTEC-2 trial was then published in 2010, which was an open-label, non-inferiority randomized control trial that compared vaginal brachytherapy (VBT) to EBRT for patients with high-intermediate risk endometrial cancer. This trial demonstrated non-inferiority of VBT compared to EBRT with no significant difference in vaginal or locoregional recurrence, overall survival, and disease-free survival. However, it did show a significant decrease in grade 1-2 gastrointestinal toxicities in the VBT group. VBT is now the standard of care given its decreased toxicity but is also notably less time-consuming for patients. Our objective was to identify if there was a difference in the administration of VBT versus EBRT for endometrial cancer patients post-hysterectomy in rural versus urban locations. <b>Methods:</b> This is a retrospective cohort study based on the SEER 18 dataset of the US National Cancer Institute. Women with localized endometrial cancer post-hysterectomy were included in this study. The SEER dataset defines a localized tumor as a tumor confined to the organ of origin without extending beyond the primary organ. Data were collected from 2011 to 2018, given that PORTEC-2 was published in 2010. Urban versus rural population was defined by the rural-urban continuum codes. Women were excluded if they received both VBT and EBRT or if a rural-urban continuum code was not provided. Statistical analysis was completed with relative risk and confidence interval calculation. <b>Results:</b> In total, 10,840 women were included. There were 9813 women identified in metropolitan counties; 22% (<i>n</i>=2136) received EBRT post-hysterectomy for localized endometrial cancer, whereas 78% underwent VBT. There were 1027 women identified in nonmetropolitan counties, 22% (<i>n</i>=230) received EBRT and 78% (<i>n</i>=797) received VBT. When comparing metropolitan versus nonmetropolitan counties, there was no statistical difference between rates of EBRT versus VBT, with a relative risk of 1.16 (95% CI: 0.91-1.16, p=0.64). There were 125 women identified in completely rural counties, 21% (<i>n</i>=26) received EBRT and 79% (<i>n</i>=99) received VBT. There was no statistical difference in rates of radiation therapy between completely rural and metropolitan counties, with a relative risk of 0.95 (95% CI: 0.67-1.34, p=0.77). <b>Conclusions:</b> Living in a nonmetropolitan county or even a completely rural county was not associated with a difference in receiving EBRT versus VBT in patients with localized endometrial cancer status post-hysterectomy compared to rates in metropolitan counties. It could be inferred that even though rural counties may have fewer medical resources, patients are still receiving the standard of care in regard to radiation therapy for endometrial cancer.

Effect of Micronutrient Concentration on the Growth of Children in Central Rural Highland of Ethiopia: Cluster Randomized Trial

The objective of study designed to concur whether micronutrient concentration change reduces the high burden of growth defect of young children age 6 to 59 after nutrition behavior exertions end in Central highland Ethiopia. We used a cluster parallel, non-inferiority randomized control trial. “Kebeles” [lower administrations] selected from central highland districts randomly assigned to either the intervention or the control cluster. At the baseline survey, 1012 children aged 6-59 months and paired mothers were selected from randomly assigned kebeles using a systematic sampling method. The intervention cluster was appointed to exploit nutrition behavior intervention through 15 months. The baseline and end-line data contained median urine iodine, hemoglobin, anthropometry, and other variables analyzed using independent t-test and Generalized Estimate Equation (GEE) using SPSS version 21 software. At the end-line, about 715 study participants completed the nutrition Behavior Change Communication (BCC) intervention. A very high (42.1%) prevalent growth defect observed at baseline and reduced to high level (28.67%) at the end-line. Baseline iodine concentration by 0.69 cm (B=0.69, P &lt; 0.05) and end-line by 0.271 cm (B=0.271, P &lt; 0.05) somewhat increased average end-line height compared to iron concentration. The difference of height (Ht) baseline – end-line between intervention and control group was 0.51 cm. Being in the intervention cluster increased Ht by 10.8 cm (beta [β] = 10.8, standard error [SE] = 1.023) than other predictors of growth of children. This community-based study implied the need for efforts to improve the linear growth of children at an early age through inspiring nutrition behavior.

Comparing Online and On-Site Cognitive Behavior Therapy in Major Depressive Disorder: Protocol for a Noninferiority Randomized Controlled Trial.

BackgroundThe incidence of mental health disorders in Canada is increasing with costs of CAD $51 billion (US $40 billion) per year. Depression is the most prevalent cause of disability while cognitive behavioral therapy (CBT) is the best validated behavioral depression treatment. CBT, when combined with mindfulness meditation (CBT-M), has strong evidence for increased efficacy. While randomized controlled trials (RCTs) have demonstrated online CBT-M efficacy, comparisons with in-office delivery are lacking.ObjectiveThe aim of this research is to assess whether online group CBT-M (with standard psychiatric care) is non-inferior in efficacy and more cost-effective than office-based, on-site group CBT-M at post-intervention and 6-months follow-up in major depressive disorder. The study will also assess whether digitally recorded data (ie, online workbooks completed, Fitbit step count, and online text messages) predict depression symptom reduction in online participants.MethodsThis single-center, two-arm, noninferiority RCT employs assessor-blinded and self-report outcomes and economic evaluation. The research site is the Centre for Addiction and Mental Health (Toronto), a research-based psychiatry institution where participants will be identified from service wait lists and through contacts with other Toronto clinics. Inclusion criteria are as follows: (1) aged 18-60 years, any ethnicity; (2) Beck Depression Inventory-II (BDI-II) of mild severity (score ≥14) with no upper severity limit; (3) Mini-International Neuropsychiatric Interview-confirmed, psychiatric major depressive disorder diagnosis; (4) fluent in English. All patients are diagnosed by staff psychiatrists. Exclusion criteria are as follows: (1) receipt of weekly structured psychotherapy; (2) observation of Diagnostic and Statistical Manual of Mental Disorders (5th Edition) criteria for severe alcohol or substance use disorder (in past 3 months), borderline personality disorder, schizophrenia (or other primary psychotic disorder), bipolar disorder, or obsessive-compulsive disorder; (3) clinically significant suicidal ideation (imminent intent or attempted suicide in the past 6 months); and (4) treatment-resistant depression. All participants receive standard psychiatric care, experimental participants receive online group CBT-M, and controls receive standard care in-office group CBT-M. The online group program (in collaboration with NexJ Health, Inc) combines smartphone and computer-accessed workbooks with mental health phone counselling (16 hours in 16 weeks) that coordinates software interactions (eg, secure text messaging and Fitbit-tracked walking). The primary outcome is BDI-II, and secondary outcomes are anxiety (Beck Anxiety Inventory), depression (ie, Quick Inventory of Depressive Symptomatology and 17-item Hamilton Depression Rating Scale), mindfulness (Five-Facet Mindfulness Questionnaire), quality of life (European Quality of Life Five Dimension), and pain (Brief Pain Inventory).ResultsBased on prior studies with the BDI-II and 80% power to reject an inferiority hypothesis with a 1-sided type I error rate of 5%, a sample of 78 per group is adequate to detect small-to-medium–effect sizes.ConclusionsThis study assesses online CBT-M efficacy and noninferiority in relation to in-person CBT, and the cost-effectiveness of both interventions.Trial RegistrationClinicalTrials.gov NCT04825535; https://www.clinicaltrials.gov/ct2/show/NCT04825535International Registered Report Identifier (IRRID)DERR1-10.2196/29726

Evaluation of the Efficacy and Safety of an Herbal Formulation for Rheumatoid Arthritis – a Non-Inferiority Randomized Control Trial

Evaluation of the Efficacy and Safety of an Herbal Formulation for Rheumatoid Arthritis – a Non-Inferiority Randomized Control Trial

Needle-free Mental Incisive Nerve Block:In vitro, Cadaveric, and Pilot Clinical Studies

The present study aimed to optimize Needle-Free Liquid Jet Injection (NFLJI) for Mental Incisive Nerve Blocks (MINB) and evaluate its clinical safety and feasibility. A MINB protocol was developed and optimized by series of NFLJI experiments in soft tissue phantoms and cadavers, then validated in two pilot Randomized Controlled Trials (RCT). The NFLJI penetration depth was found to be directly proportional to the supply pressure and volume. High-pressure NFLJIs (620 kPa or above) created maximum force and total work significantly greater than needle injections. Low-pressure NFLJIs (413 kPa), however, produced results similar to those of needle injections. Additionally, high-pressure NFLJIs created jet impingement pressure and maximum jet penetration pressure higher than low-pressure NFLJIs. Pilot RCTs revealed that high-pressure NFLJI caused a high risk of discomfort (60%) and paresthesia (20%); meanwhile, low-pressure NFLJI was less likely to cause complications (0%). The preliminary success rates of MINB from cadavers using NFLJIs and needles were 83.3% and 87.5%. In comparison, those from RCTs are 60% and 70%, respectively. To conclude, NFLJI supply pressure can be adjusted to achieve effective MINB with minimal complications. Furthermore, the cadaver study and pilot RCTs confirmed the feasibility for further non-inferiority RCT.

Needle-free injection: Dental infiltration anesthesia

This study aimed to develop an optimal Needle-Free Liquid Jet Injection (NFLJI) technique for dental infiltration anesthesia and evaluate its clinical safety and feasibility. The fluid dynamics of NFLJI in the dentoalveolar region were investigated using soft tissue phantoms supported by rigid glass. NFLJIs were performed at different incident angles and recorded using a high-speed camera. Accordingly, an optimal NFLJI for infiltration anesthesia was developed and validated on cadavers, then assessed in two pilot Randomized Controlled Trials (RCT): one for validating the safety of optimal NFLJI technique, the other for evaluating its feasibility and safety. High-speed videos showed that perpendicular NFLJIs induced significantly more regurgitation than oblique NFLJIs, which was confirmed in cadavers. Clinical trials revealed that perpendicular NFLJIs induced a high risk of bleeding (83.3%) and laceration (83.3%), whereas oblique NFLJIs induced a low risk of bleeding (33.3%) and laceration (16.7%). Moreover, the preliminary success rates of oblique NFLJIs and needle injections were both 83.3%. The recruitment took 3–5 weeks with a rate of 100%. Oblique NFLJIs could be a promising approach for dental infiltration anesthesia, causing minimal drug regurgitation with a relatively low risk of complication. The pilot RCTs confirmed the feasibility for conducting a non-inferiority RCT.

Is a homemade cardiopulmonary resuscitation (CPR) trainer non-inferior to a commercially available CPR mannequin in teaching high-quality CPR? A non-inferiority randomized control trial

IntroductionStudies demonstrate that feedback devices help students achieve mastery of critical CPR skills and shorten the time from demonstration to competence. CPR feedback devices are costly and may not be available in low resource settings or in the context of online classes. We have developed a homemade feedback enabled CPR trainer. This trainer consists of a lid with two toilet rolls stacked on top. We have shown it is feasible to generate high quality CPR using this trainer, however the ability for this trainer to successfully be used in skill acquisition is unknown.Our main objective was to assess if learning CPR on a homemade toilet paper trainer was non-inferior to a commercially available mannequin when comparing post-training CPR scores. MethodsWe conducted a parallel non-inferiority randomized control trial using a variable block randomization to a 10-min training session on either a toilet paper or commercial mannequin trainer. Primary outcome was mean overall CPR score as determined by high fidelity mannequin software. A sample size of 62 per group was calculated based on a 90% power to assess for the lower limit of a two-sided 95% confidence interval above the non-inferiority limit of 10%. Results125 participants were randomized to the toilet paper (n = 64) or commercial mannequin trainer (n = 61). There was no difference between groups in age, sex, height, weight or previous CPR training. There was an absolute difference of 2% (CI 95% 3.3 to 7.3%) in mean overall CPR score between groups (toilet paper = 82% (SD 15.9%), commercial mannequin = 84% (SD 15%). ConclusionA homemade CPR trainer was non-inferior to a commercially available trainer. This study provides preliminary evidence supporting the use of a homemade, easily accessible trainer for basic compression-only CPR skill acquisition.

A comparison of the efficacy of normal saline and Savlon solutions in periurethral cleaning to reduce catheter-associated bacteriuria: A randomized control trial

ObjectiveCatheter-associated urinary tract infection (CAUTI) is a common nosocomial infection. However, there has been no randomized control trial (RCT) comparing the efficacy of periurethral cleaning solutions for reducing CAUTI. This study aimed to compare the efficacy of normal saline solution (NSS) and Savlon solution. MethodsA non-inferiority cross-over RCT was conducted to compare the 2 solutions by the incidence of significant bacteriuria (SB) on day 5 after Foley catheterization. Patients admitted to a tertiary referral hospital from June 2018 to August 2019 participated in the study. The acceptable prespecified non-inferiority margin was 10%. ResultsThere were 265 and 275 patients in the NSS and Savlon groups, respectively. The incidence of CAUTI was 2.65/1000 catheter-days, and the median duration of catheterization was 5 days (IQR 4, 7). There was no significant difference between the incidence of SB in the NSS and Savlon groups, as indicated by the adjusted difference of 0.6 (95% CI: -3.1-4.2). ConclusionThis study was the first RCT in patients from multiple hospital units to compare the efficacy of the 2 solutions in the periurethral cleaning process. The study demonstrated non-inferiority of NSS to Savlon solution. Thai Clinical Trials Registry Study IDTCTR20180518001.

Levetiracetam Versus Fosphenytoin as a Second-Line Treatment After Diazepam for Adult Status Epilepticus: A Multicenter Non-Inferiority Randomized Control Trial

Levetiracetam Versus Fosphenytoin as a Second-Line Treatment After Diazepam for Adult Status Epilepticus: A Multicenter Non-Inferiority Randomized Control Trial

Methodological and Reporting Quality of Noninferiority Randomized Controlled Trials Comparing Antibiotic Therapies: A Systematic Review.

Antibiotic noninferiority randomized controlled trials (RCTs) are used for approval of new antibiotics and making changes to antibiotic prescribing in clinical practice. We conducted a systematic review to assess the methodological and reporting quality of antibiotic noninferiority RCTs. We searched MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and the Food and Drug Administration drug database from inception until November 22, 2019, for noninferiority RCTs comparing different systemic antibiotic therapies. Comparisons between antibiotic types, doses, administration routes, or durations were included. Methodological and reporting quality indicators were based on the Consolidated Standards of Reporting Trials reporting guidelines. Two independent reviewers extracted the data. The systematic review included 227 studies. Of these, 135 (59.5%) studies were supported by pharmaceutical industry. Only 83 (36.6%) studies provided a justification for the noninferiority margin. Reporting of both intention-to-treat (ITT) and per-protocol (PP) analyses were done in 165 (72.7%) studies. The conclusion was misleading in 34 (15.0%) studies. The studies funded by pharmaceutical industry were less likely to be stopped early because of logistical reasons (3.0% vs 19.1%; odds ratio [OR] = 0.13; 95% confidence interval [CI], .04-.37) and to show inconclusive results (11.1% vs 42.9%; OR = 0.17; 95% CI, .08-.33). The quality of studies decreased over time with respect to blinding, early stopping, reporting of ITT with PP analysis, and having misleading conclusions. There is room for improvement in the methodology and reporting of antibiotic noninferiority trials. Quality can be improved across the entire spectrum from investigators, funding agencies, as well as during the peer-review process.There is room for improvement in the methodology and reporting of antibiotic noninferiority trials including justification of noninferiority margin, reporting of intention-to-treat analysis with per-protocol analysis, and having conclusions that are concordant with study results.Clinical Trials Registration PROSPERO registration number CRD42020165040.

Methodological aspects of superiority, equivalence, and non-inferiority trials.

Depending on the scientific hypothesis to be addressed, randomized-controlled trials (RCT) are accordingly designed. RCTs that aim to determine whether a novel, experimental therapeutic intervention (either a drug or a treatment) is superior to a placebo or control intervention, are called superiority trials. Less common are the non-inferiority RCTs, designed to assess whether a new intervention is not unacceptably worse than an already existing reference intervention. An equivalence RCT is designed to investigate whether a novel treatment is equivalently effective to another, already existing, control intervention. In equivalence and non-inferiority RCTs, the efficacy of the reference intervention (active comparator) is already established, and therefore, an untreated control group would not be ethical. In this review, using a series of examples derived from equivalence and non-inferiority/superiority RCTs, we describe the main differences and methodological aspects among these three different types of RCTs.

Review of the use of prophylactic drain tubes post‐robotic radical prostatectomy: Dogma or decent practice?

ObjectiveTo assess the necessity of routine prophylactic drain tube use following robot‐assisted radical prostatectomy (RARP).MethodWe performed a literature review using the Medline, Scopus, and Web of Science databases with no restriction of language from January 1900 to January 2020. The following terms we used in the literature search: prostatectomy, radical prostatectomy, robot assisted, drainage, and drain tube.ResultsWe identified six studies that examined the use of routine prophylactic drain tubes following RARP. One of these studies was a randomized study that included 189 patients, with 97 in the pelvic drain (PD) arm and 92 in the no pelvic drain (ND) arm. This non‐inferiority showed an early (90‐day) complication rate of 17.4% in the ND arm versus 26.8% in the PD arm (P < .001). Another non‐inferiority randomized control trial (RCT) showed a complication rate of 28.9% in the PD group versus 20.4% in the ND group (P = .254). Similarly, the other studies found no benefit of routine use of prophylactic drain tube after RARP.ConclusionDrain tubes play a role during robotic‐assisted radical prostatectomy, however, following a review of the current available literature, they can be safely omitted and we suggest that clinicians may be selective in their use.