Controlled Noninferiority Trial Research Articles

P0659 Exploring Ferric Maltol: A Promising Alternative to IV Iron for Managing Chronic Iron Deficiency Anaemia in Inflammatory Bowel Disease Patients

Abstract Background Around 500,000 people in the UK have inflammatory bowel disease (IBD), with one in three affected by iron deficiency anemia (IDA), which leads to fatigue and increased hospital admissions1. Literature recommends timely treatment based on haemoglobin (HB) and ferritin levels4. First-line treatment with iron salts cause side effects, while intravenous (IV) options with IV iron are logistically challenging. Feraccru (oral ferric maltol) offers a promising alternative, improving HB levels in IBD patients, supported by clinical trial data in AEGIS and FRESH study2,3. This study evaluates the safety, tolerability and effectiveness of Feraccru for managing IDA in IBD patients. Methods Patients with mild to moderate IDA secondary to Crohn’s Disease (CD) or Ulcerative Colitis (UC) after failing oral iron salts, were included and prescribed Feraccru 30 mg twice daily. Data was retrospectively collected from electronic records between January 1, 2021, and April 2024. Baseline Hb and ferritin levels were recorded at the start of treatment and at 12 weeks with follow-up between 6–12 months to assess the need for IV iron or blood transfusions. Clinical response was defined as normalisation of HB levels (Male ≥130g/l, female ≥120g/l) and serum ferritin levels (>30 µg/L). Results A total of 83 patients (31 males, 52 females) were enrolled in the study. Of these, 70% (n=58/83) achieved normalisation of HB levels, and 55% (n=44/80) achieved normalisation of serum ferritin. A higher rate of male patients (77%, n=24/31) achieved Hb normalisation compared to females (65%, n=34/52), while females exhibited a higher rate of serum ferritin normalisation (59%, n=29/49) compared to males (48%, n=15/31) as shown in Figure 1. Of the 25 patients who did not achieve clinical response by week 12, 5 discontinued treatments due to adverse events (AEs) and 30% (n=6) who continued for an additional 24 weeks, achieving HB normalisation. A total of 8 AEs were reported which included: 64% stomach cramps (n=5), 12% (n=1) loose stools, 12% (n=1) constipation and 12% (n=1) rectal bleeding as displayed in Figure 2. No serious adverse events (SAEs) were observed. Additionally, only 23% (n=19/83) of patients received IV iron 6–12 months following Feraccru treatment. Conclusion Feraccru was effective in treating IDA in patients with IBD, with 70% achieving HB normalisation and 55% normalising serum ferritin. Adverse events were mild, with no serious events. Only 23% of patients required IV iron, reducing the risk of adverse events, lowering costs, and avoiding the logistical challenges of hospital-based treatments. Feraccru should be considered as an option for IBD patients prior to referring for IV iron. References Crohn’s & Colitis UK. Crohn’s & Colitis UK [Internet]. www.crohnsandcolitis.org.uk. 2022. Available from: https://crohnsandcolitis.org.uk/Gasche C, Berstad A, Befrits R, Beglinger C, Dignass A, Erichsen K, et al. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflammatory Bowel Diseases. 2007 Dec;13(12):1545–53.Howaldt S, Domènech E, Martinez N, Schmidt C, Bokemeyer B. Long-Term Effectiveness of Oral Ferric Maltol vs Intravenous Ferric Carboxymaltose for the Treatment of Iron-Deficiency Anemia in Patients with Inflammatory Bowel Disease: A Randomized Controlled Noninferiority Trial. Inflammatory Bowel Diseases. 2021 May 14.NICE. Anaemia - Iron deficiency [Internet]. NICE. 2021. Available from: https://cks.nice.org.uk/topics/anaemia-iron-deficiency/

Immersive Virtual Reality Versus Mannequin-based Simulation Training for Trauma Resuscitation: A Randomized Controlled Noninferiority Trial.

Despite its high potential, the effect of immersive virtual reality simulation (VRS) in trauma resuscitation training has not been studied. The aim of this study was to test the hypothesis that VRS is non-inferior to mannequin-based simulation (MBS) in trauma resuscitation training. In a single-center, randomized controlled noninferiority trial, we compared individual training with an immersive virtual reality Trauma Simulator to live MBS training in a facilitated group. The primary outcome was the Trauma Score (ranging from 55 to 177) during the MBS assessment. The secondary outcomes were the Trauma Score VRS assessment, System Usability Scale (SUS) (ranging from 0 to 100), and Simulation Sickness Questionnaire (SSQ) (ranging from 0 to 235.62). A total of 38 participants were enrolled in the study. The mean Trauma Score in MBS assessment was 163.2 (SD 7.9) for the control group and 163.1 (SD 13.8) for the intervention group; the difference of means 0.1 (95% confidence interval: -7.3, 7.5; P = .977). The mean Trauma Score in VRS assessment was 134.2 (SD 24.4) for control group and 158.4 (SD 17.6) for intervention group; the difference of means 24.2 (95% confidence interval: 10.1, 38.3; P = .001). The mean SUS of Trauma Simulator was 74.4 (SD 10.5). The median SSQ Total Severity score was 3.7 (IQR 0-18.7). This study showed that VRS led to noninferior effects on trauma resuscitation skills to MBS. Trauma Simulator had good usability, was well received by the participants, and had minimal adverse effects.

Comparison of Ultrasound-guided Single-injection Erector Spinae Plane Block, Retrolaminar Block, and Paravertebral Block for Postoperative Analgesia in Single-incision Video-assisted Thoracoscopic Surgery: A 3-arm, Double-blind, Randomized Controlled Noninferiority Trial.

Effective postoperative analgesia is critical for thoracic surgery. This study compares the analgesic efficacy of the erector spinae plane block (ESPB), retrolaminar block (RLB), and paravertebral block (TPVB) in single-incision video-assisted thoracoscopic surgery (SITS). Seventy-six patients underwent general anesthesia followed by ultrasound-guided nerve blocks with 20mL of 0.5% ropivacaine. Primary outcomes included the area under the curve (AUC) of numeric rating scale (NRS) scores during rest and coughing over 24 hours. Secondary outcomes included perioperative opioid use, plasma biomarkers, and postoperative recovery measures. The AUC for NRS was 107.8±10.53 in the ESPB group, 104.8±8.05 in the RLB group, and 103.6±10.42 in the TPVB group, demonstrating noninferiority for ESPB (difference: 4.2±3.0, 95% CI: -1.82 to 10.22) and RLB (difference: 1.2±2.6, 95% CI: -3.97 to 6.37) compared with TPVB. No statistically significant differences were observed in opioid use, plasma biomarkers, QoR-15 scores, or adverse events. ESPB and RLB provide noninferior analgesia compared with TPVB in SITS patients and are effective alternatives that enhance safety.

Misoprostol as Oral Solution or Oral Tablet for Induction of Labour (MISOBEST): A Randomised Controlled Non-Inferiority Trial.

To assess if off-label oral solution of misoprostol compared with licensed oral tablet of misoprostol approved for induction of labour (IOL) is as efficient in resulting in vaginal delivery within 24 h, using a non-inferiority design. Prospective, randomised, non-inferiority, open-label, blinded endpoint trial. Two tertiary level hospitals, Stockholm, Sweden, January 2022 to May 2023. In all, 874 women, without previous caesarean section, with an unripe cervix and a singleton, cephalic foetus at 37 + 0 to 42 + 0 gestational weeks, with a normal cardiotocography, planned for IOL were included. Women were randomised 1:1 to intervention (25 μg oral solution of misoprostol) or control (25 μg oral tablet of misoprostol) two-hourly for a maximum of eight doses. Subsequent methods of induction followed clinical practice. The primary outcome was vaginal delivery within 24 h tested using non-inferiority testing procedures at a non-inferiority margin of 5 percentage points. Secondary efficacy outcomes were tested for superiority of either treatment. Analyses were by intention-to-treat. There were 207 (47.4%) vaginal deliveries within 24 h for women receiving oral solution and 192 (43.9%) vaginal deliveries within 24 h for women receiving oral tablet, establishing non-inferiority with an absolute risk difference of 3.4% (95% CI -3.2% to 10.0%). Women receiving oral solution required fewer doses to reach active labour than women receiving oral tablet (5.7 vs. 6.1, p = 0.007). There were no significant differences for other secondary or safety outcomes. Off-label oral solution of misoprostol was non-inferior to the licensed oral tablet regarding efficacy of IOL defined as vaginal delivery within 24 h. Clinicaltrials.gov identifier: NCT05424445.

Electroacupuncture versus solifenacin succinate for female overactive bladder: study protocol for a multicentre, randomised, controlled, double-dummy, non-inferiority trial

IntroductionOveractive bladder (OAB) affects approximately 500 million people worldwide, with a higher prevalence in women than in men, significantly impacting the quality of life of female patients. Treatment options for...

Safety and feasibility of triage and rapid discharge of patients with chest pain from emergency room: A pragmatic, randomized noninferiority control trial of the European Society of Cardiology (ESC) 0 to 1 hour pathway vs conventional 0 to 3 hour accelerated diagnostic protocol

Patients presenting with chest pain represent a significant proportion of Emergency Department (ED) attendances but only a minority, typically 10%, have a final diagnosis of myocardial infarction (MI). Prompt discharge of patients without MI will alleviate ED overcrowding as well as improve patient satisfaction and reduce exposure to risk of hospital acquired infections such as Covid 19.The measurement of cardiac troponin (cTn) by a high sensitivity method is recommended by the National Institute for health and Care Excellence (NICE) for rapid categorisation of patients presenting with chest pain. Strategies proposed include measurement on admission and one hour from admission (ESC 0–1-hour pathway, the recent guideline approved pathway which has not been implemented widely), and measurement on admission and three hours from admission (0–3-hour pathway, which is conventional and widely adopted).The primary objective of this study is twofold: firstly, to assess the safety, feasibility, and impact of implementing the ESC (European Society of Cardiology) 0–1-hour pathway in clinical practice by reference to the more established ESC 0–3-hour protocol. The principal outcome measure will be the safety of the ESC 0–1-hour protocol. However, there are concerns that the time from sample draw to result availability (typically around 60 minutes) will impact on the feasibility of the ESC 0–1-hour pathway. Secondly, therefore, our goal is to evaluate whether measurement of high sensitivity troponin by a bedside analyser (point of care testing, POCT), which will produce results in 15 minutes is a feasible alternative to laboratory testing. We will compare the results produced by POCT with the laboratory results in the context of the ESC 0-1 hour and 0–3-hour pathway, as a nested controlled study in the context of a randomised controlled trial. (clinicaltrials.gov: NCT05322395)

In-Person Versus Online Training in Simulations of Helping Babies Breathe: A Randomized Controlled Trial.

Birth asphyxia is a leading cause of neonatal deaths, but simple interventions may prevent it. The Helping Babies Breathe (HBB) course has significantly reduced neonatal mortality ratesin lower and middle-income countries (LMICs) by training healthcare providers (i.e. midwives and nurses) on the essential skills of bag-and-mask ventilation and postnatal care. Although several studies have supported the efficacy of virtual learning in other medical education programs, there is still a lack of knowledge regarding a virtual approach to HBB. This study aims to compare the effectiveness of online versus in-person learning of the HBB course among medical and nursing students. The study is a two-arm parallel randomized non-inferiority controlled trial, that includes medical and nursing students. Participants were randomly assigned to either online or in-person debriefing during the hands-on simulations of HBB. They attended a pre-recorded lecture before being assigned to one of three instructors for the simulation lab. Participants completed a seven-point anonymous Likert-based questionnaire and a standardized Debriefing Assessment for Simulation in Healthcare Student Version (DASH-SV) Short Form. The primary outcome was the Objective Structured Clinical Exam (OSCE) grade. The trial is listed on ClinicalTrials.gov with the registration number NCT05257499. 47 participants completed the study, with similar baseline characteristics in each arm (gender, age, and class). The participants in both arms reported high levels of satisfaction and confidence, with no significant difference between the two arms. The DASH score over 7 was also similar in the online arm(6.27±0.26) compared to the in-person arm (6.55±0.13) (p=0.07). The mean OSCE scorein the online arm (45.8±5.2) was comparable to the mean OSCE score in the in-person arm (41.3±5.0) (p=0.22). Both online and in-person participants failed the OSCE. The survey responses conveyed that online simulation training is comparable to in-person simulation for the HBB course. Both online and in-person participants failed the OSCE most likely because they needed more training on HBB. This could be due to the fact that the material is too new to the students who needed more practice to pass the OSCE. Further research is needed to confirm these results and explore the long-term impact of online neonatal resuscitation training.

Transcutaneous neuromodulation versus oxybutynin for neurogenic detrusor overactivity in persons with spinal cord injury: A randomized, investigator blinded, parallel group, non-inferiority controlled trial

Study design This study is a randomized, investigator-blinded, controlled trial with a non-inferiority design. Objective To investigate the effectiveness of neuromodulation by transcutaneous electrical stimulation of the somatic afferent nerves of the foot in neurogenic detrusor overactivity (NDO) in persons with spinal cord injury (SCI) and compare its effectiveness with oral oxybutynin. Setting The study was conducted in a rehabilitation in-patient ward of a tertiary care hospital. Methods Twenty-nine persons with SCI with NDO, either sex, aged 18 years and above were randomized into two groups, one group receiving oral oxybutynin (5 mg thrice a day for two weeks) and the other transcutaneous electrical stimulation (5 Hz, 200 µs pulse, biphasic, amplitude up to 60 mA, 30 min/day for two weeks). Bladder capacity was evaluated by clinical bladder evaluation (i.e. bladder capacity measured by adding leak volume, voiding volume if any, and post-void residue using a catheter) and cystometric bladder capacity by one-channel cystometry. Maximum cystometric pressure was evaluated by one-channel water cystometry. Data were analyzed with Fisher's Exact, t-test, and Wilcoxon rank sum tests. Results Bladder capacity improved significantly in the oxybutynin and neuromodulation groups as measured by one-channel water cystometry (136 ml vs. 120.57 ml) and clinical evaluation (138.93 ml vs. 112 ml). The increase in the neuromodulation group achieved the pre-decided non-inferiority margin of 30 ml over the oxybutynin group when measured by one-channel water cystometry but not by clinical evaluation. Maximum cystometric pressure did not significantly improve in either group when compared with the baseline. Conclusion Transcutaneous neuromodulation and oxybutynin effectively increased bladder capacity in persons with SCI with NDO. Neuromodulation by once-a-day transcutaneous electrical stimulation was non-inferior to thrice-a-day oxybutynin when evaluated by one-channel water cystometry. Trial registration: Clinical Trials Registry India identifier: CTRI/2018/05/013735.

State of the Science: Evidence‐based treatments for posttraumatic stress disorder delivered via telehealth

AbstractPsychotherapy delivered via telehealth technology is not an artifact of the COVID‐19 pandemic. Indeed, widespread, telehealth‐delivered, evidence‐based psychotherapy preceded the pandemic, as did randomized controlled noninferiority trials supporting this modality. It is, thus, not difficult to predict that telehealth will be an integral part of daily clinical life moving forward. With respect to posttraumatic stress disorder (PTSD) specifically, there is a substantial number of studies on the feasibility, acceptability, and effectiveness of evidence‐based treatments provided via videoconferencing. In this review, we delineate the literature establishing strong support for remote delivery of prolonged exposure (PE) and cognitive processing therapy (CPT); there is also promising support for written exposure therapy (WET) and trauma‐focused cognitive behavioral therapy (TF‐CBT). We also mention adjunctive and integrative modifications to better serve patients with PTSD. One such intervention, behavioral activation and therapeutic exposure (BATE), has several studies supporting telehealth delivery, whereas concurrent treatment of PTSD and substance use disorders using the PE protocol (COPE) and cognitive behavioral therapy for insomnia (CBT‐I) would benefit from further research. Integrating instrumental peer support into telehealth‐delivered PE shows promise in retaining patients in treatment. Finally, we provide ideas to maximize telehealth delivery effectiveness, explore future research directions, and discuss ways to advocate for the expansion of telehealth services from an equity perspective.

MP20-19 Bipolar Enucleation of the Prostate (BipolEP) versus Transurethral Resection of the Prostate: A Prospective Randomized Controlled Non-Inferiority Trial

MP20-19 Bipolar Enucleation of the Prostate (BipolEP) versus Transurethral Resection of the Prostate: A Prospective Randomized Controlled Non-Inferiority Trial

Feeds Alone versus Intravenous Fluids and Feeds for Treatment of Mild Hypernatremia in Otherwise Healthy Neonates – An Open-labeled Randomized Controlled Noninferiority Trial

Background: The treatment of hypernatremia in newborns is usually done by giving intravenous (IV) fluids. Methodology: This study aimed to determine whether treating neonates with hypernatremia using oral feeds was not inferior by a margin of 10% to treatment with IV fluids and feeds in achieving a safe decline in serum sodium. A decrease in serum sodium ≤0.5 mEq/L/h over 24 h of treatment was considered a safe decline. Neonates with serum sodium 150–155 mEq/L were randomized to receive oral feeds ad libitum (Group A) or 5% dextrose +0.45% normal saline (D5 ½ NS) and oral feeds (group B). Results: There were 43 neonates in Group A and 42 neonates in Group B. It was found that a safe decline in serum sodium was seen in 60.5% of Group A neonates and 47.6% of Group B neonates (P = 0.246). There was no significant difference in the duration of treatment or duration of hospital stay. Group B babies had more weight gain compared to Group A. No complications were observed in the groups. Conclusion: Treating mildly hypernatremic neonates with serum sodium 150–155 mEq/L using oral feeds alone may not be inferior to IV fluids with oral feeds in achieving a safe decline in serum sodium.

Efficacy and safety comparison of infrared laser moxibustion and traditional moxibustion in knee osteoarthritis: study protocol for a Zelen-design randomized controlled non-inferiority clinical trial

BackgroundKnee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA.Materials and methodsIn the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial.ConclusionThe results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future.Trial registration: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.

Online-Mediated HIV Pre-exposure Prophylaxis Care and Reduced Monitoring Frequency for Men Who Have Sex With Men: Protocol for a Randomized Controlled Noninferiority Trial (EZI-PrEP Study).

Daily and event-driven HIV pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine is highly effective to prevent HIV in men who have sex with men (MSM). PrEP care generally consists of in-clinic monitoring every 3 months that includes PrEP dispensing, counseling, and screening for HIV and sexually transmitted infections (STIs). However, the optimal frequency for monitoring remains undetermined. Attending a clinic every 3 months for monitoring may be a barrier for PrEP. Online-mediated PrEP care and reduced frequency of monitoring may lower this barrier. The primary objective of this study is to establish the noninferiority of online PrEP care (vs in-clinic care) and monitoring every 6 months (vs every 3 months). The secondary objectives are to (1) examine differences between PrEP care modalities regarding incidences of STIs, HIV infection, and hepatitis C virus infection; retention in PrEP care; intracellular tenofovir-diphosphate concentration; and satisfaction, usability, and acceptability of PrEP care modalities; and (2) evaluate associations of these study outcomes with sociodemographic, behavioral, and psychological characteristics. This study is a 2×2 factorial, 4-arm, open-label, multi-center, randomized, controlled, noninferiority trial. The 4 arms are (1) in-clinic monitoring every 3 months, (2) in-clinic monitoring every 6 months, (3) online monitoring every 3 months, and (4) online monitoring every 6 months. The primary outcome is a condomless anal sex act with a casual partner not covered or insufficiently covered by PrEP (ie, "unprotected act") as a proxy for HIV infection risk. Eligible individuals are MSM, and transgender and gender diverse people aged ≥18 years who are eligible for PrEP care at 1 of 4 participating sexual health centers in the Netherlands. The required sample size is 442 participants, and the planned observation time is 24 months. All study participants will receive access to a smartphone app, which contains a diary. Participants are requested to complete the diary on a daily basis during the first 18 months of participation. Participants will complete questionnaires at baseline and 6, 12, 18, and 24 months. Dried blood spots will be collected at 6 and 12 months for assessment of intracellular tenofovir-diphosphate concentration. Incidence rates of unprotected acts will be compared between the online and in-clinic arms, and between the 6-month and 3-month arms. Noninferiority will be concluded if the upper limit of the 2-sided 97.5% CI of the incidence rate ratio is <1.8. The results of the main analysis are expected in 2024. This trial will demonstrate whether online PrEP care and monitoring every 6 months is noninferior to standard PrEP care in terms of PrEP adherence. If noninferiority is established, these modalities may lower barriers for initiating and continuing PrEP use and potentially reduce the systemic burden for PrEP providers. ClinicalTrials.gov NCT05093036; https://tinyurl.com/28b8ndvj. DERR1-10.2196/51023.

Wearable Integrated Volitional Control Electrical Stimulation Device as Treatment for Paresis of the Upper Extremity in Early Subacute Stroke Patients: A Randomized Controlled Non-inferiority Trial

ObjectiveTo investigate the effect of a wearable integrated volitional control electrical stimulation (WIVES) device that has been developed as more compact and simpler to use in daily life compared with conventional integrated volitional control electrical stimulation (IVES) devices. DesignRandomized controlled non-inferiority trial. SettingConvalescent rehabilitation ward. ParticipantsPatients with paresis of the upper extremity (UE) after early subacute stroke (N=20). InterventionsEligible patients were randomized to receive IVES treatment or WIVES treatment for 8 hours per day for 28 days in daily living, in addition to standard rehabilitation treatment. In both groups, the extensor digitorum communis on the affected side was the target muscle for stimulation. Main Outcome MeasurePrimary outcomes were assessed with Fugl–Meyer Assessment of the UE (FMA-UE) before and after treatment. Non-inferiority was determined with a specified margin of non-inferiority. ResultsTwenty patients completed the trial (IVES group: n=10, WIVES group: n=10). FMA-UE improved in both groups. The mean change in FMA-UE was 4.7 for the IVES group and 6.0 for the WIVES group (P>.05, 95% confidence interval: −6.73 to 4.13). The mean difference between the groups was 1.3, and the upper 95% confidence interval did not exceed the non-inferiority margin. ConclusionThe effectiveness of WIVES treatment is non-inferior to that of IVES treatment. As a portable device, IVES may facilitate the use of affected upper extremities in daily living and may help improve paresis of the UE.

Robot-assisted Simple Enucleation Versus Standard Robot-assisted Partial Nephrectomy for Low- or Intermediate-complexity, Clinical T1 Renal Tumors: A Randomized Controlled Noninferiority Trial

BackgroundAlthough partial nephrectomy has become the gold standard for T1 renal tumors whenever technically feasible, simple enucleation has shown superior results. To the best of our knowledge, no randomized controlled trials comparing these two surgical approaches have been published. ObjectiveTo compare the surgical margin status for robot-assisted simple enucleation (RASE) and standard robot-assisted partial nephrectomy (sRAPN) for clinical T1 renal tumors. Design, setting, and participantsThis is a prospective, randomized, controlled, noninferiority trial. A total of 380 patients aged 18–80 yr with newly diagnosed, sporadic, unilateral clinical T1 renal tumors (RENAL score <10) were enrolled and randomized to RASE or sRAPN. The primary endpoint was the positive surgical margin (PSM) rate, with a noninferiority margin of 7.5% set. The study was registered on ClinicalTrials.gov (NCT03624673). Outcome measurements and statistical analysisWe defined noninferiority for RASE versus standard RAPN as an upper 95% confidence interval (CI) bound of <7.5% for the difference in the proportion of patients with a PSM. Results and limitationsA cohort of 380 patients was enrolled and randomly assigned to RASE (n = 190) or sRAPN (n = 190). On intention-to-treat analysis for patients with malignant tumors, 2.3% of patients in the RASE group and 3.0% in the sRAPN group had a PSM. The RASE group showed noninferiority to the sRAPN group within a 7.5% margin (difference −0.7%, 95% CI −4.0% to 2.7%). Per-protocol analysis also demonstrated noninferiority of RASE. The RASE group had a shorter median operative time (145 vs 155 min; p = 0.018) and a lower rate of tumor bed suturing (8.9% vs 43%; p < 0.001) in comparison to the sRAPN group. Estimated blood loss was considerably lower in the sRAPN group than in the RASE group (p = 0.046). The rate of recurrence did not differ between the groups (p > 0.9). ConclusionsRASE for the management of low- to intermediate-complexity tumors is noninferior to sRAPN in terms of the PSM rate. Long-term follow-up is needed to draw conclusions regarding oncological outcomes. Patient summaryWe carried out a trial to compare simple tumor enucleation versus partial nephrectomy for renal tumors. The outcome we assessed was the proportion of patients with a positive surgical margin. Our results show that simple tumor enucleation is not inferior to partial nephrectomy for this outcome. Longer follow-up is needed to assess other cancer control outcomes.

Selective Removal to Soft Dentine versus Full Pulpotomy for Management of Proximal Deep Carious Lesions: A Randomized Controlled Non-Inferiority Trial

The management of the deep carious lesion with reversible pulpitis is a dilemma for the dentist. The current study compared selective removal to soft dentine (SRSD) and full pulpotomy (FP) for treating proximal deep carious lesions in teeth with reversible pulpitis. Visual-tactile examination and bitewing radiographs were used to determine the depth of carious lesion, and American Association of Endodontists recommendations were used to formulate pulp diagnosis. Sixty mandibular molar teeth from healthy patients between the ages of 16–35 years and a diagnosis of proximal deep carious lesion with reversible pulpitis were included. Teeth were randomly allocated to two study groups. SRSD group (n = 30): soft dentine was preserved over the pulpal aspect. A hard-setting calcium hydroxide cement liner and resin-modified glass ionomer cement base were applied over the remaining soft carious dentine. FP group (n = 30): complete caries removal followed by mineral trioxide aggregate FP was performed. The teeth in both groups were restored with composite resin restoration. The established criteria for outcome assessment of SRSD and pulpotomy were used. Accordingly, only asymptomatic teeth with no radiological evidence of periapical rarefaction were considered successful at the 12-month follow-up. Two-sample t test, Pearson χ² test/Fisher’s exact test, and percentage agreement were used for statistical evaluation. According to the per-protocol analysis, the success rate of both SRSD and FP treatment was 95.45% and 95.65%, respectively, and the actual difference between the two treatments was 1% (95% CI: [−10, 9]). The data suggests that both treatments (SRSD and FP) appear to have a good success rate (>95%) when used to manage permanent mandibular molar teeth with proximal deep carious lesion and reversible pulpitis. As SRSD is a noninvasive procedure, it should be favored over FP in these instances.

Is a Lower Dose of More Bioavailable Iron (18-mg Ferrous Bisglycinate) Noninferior to 60-mg Ferrous Sulfate in Increasing Ferritin Concentrations While Reducing Gut Inflammation and Enteropathogen Detection in Cambodian Women? A Randomized Controlled Noninferiority Trial

BackgroundGlobal guidelines recommend untargeted iron supplementation for women in regions of anemia prevalence ≥40%, such as Cambodia. However, the potential harms of untargeted iron on the gut have not been rigorously studied in women and likely vary depending on iron dose and form. ObjectivesWe investigated if a lower dose of a highly bioavailable iron amino acid chelate was as effective as the standard dose of iron salts in increasing ferritin concentrations and whether any differences were observed in gut inflammation or enteropathogen detection. MethodsA double-blind, randomized placebo-controlled noninferiority trial was conducted in Cambodia. Nonpregnant women (n = 480, 18–45 y) were randomly assigned to 60-mg ferrous sulfate, 18-mg ferrous bisglycinate, or placebo for 12 wk. Nonfasting blood and stool specimens were collected at baseline and 12 wk. Ferritin and fecal calprotectin were measured with an ELISA. A molecular assay was used to detect 11 enteropathogens in a random subset of n = 100 women. Generalized linear mixed-effects models were used to estimate the adjusted mean difference in ferritin concentrations at 12 wk (primary outcome), as compared with our ‘a priori’ noninferiority margin of 20 μg/L. ResultsBaseline anemia and iron deficiency prevalence was low (17% and 6%, respectively). The adjusted mean difference in ferritin concentrations between the iron groups was 14.6 (95% confidence interval [CI]: 7.6, 21.6) μg/L. Mean ferritin concentration at 12 wk was higher in the ferrous sulfate (99 [95% CI: 95, 103] μg/L, P < 0.001) than in ferrous bisglycinate (84 [95% CI: 80, 88] μg/L) and placebo groups (78 [95% CI: 74, 82] μg/L). No differences in fecal calprotectin concentrations or enteropathogen detection were observed across groups at 12 wk. ConclusionsFerrous bisglycinate (18-mg) was not as effective as ferrous sulfate (60-mg) in increasing ferritin concentrations and did not differentially influence biomarkers of gut health in this predominantly iron-replete population of Cambodian women.This trial was registered at clinicaltrials.gov registry as NCT04017598.

Robot-assisted Partial Nephrectomy with the Newly Developed KangDuo Surgical Robot Versus the da Vinci Si Surgical System: A Double-center Prospective Randomized Controlled Noninferiority Trial

BackgroundThe KangDuo surgical robot (KD-SR) was recently developed in China. ObjectiveTo compare the safety and efficacy of the KD-SR versus the da Vinci Si Surgical System (DV-SS-Si) for robot-assisted partial nephrectomy (RAPN). Design, setting, and participantsA double-center prospective randomized controlled noninferiority trial of patients aged 18–75 yr with a suspicion of T1a N0M0 renal cancer (RENAL nephrometry score ≤9) was conducted. InterventionRAPN with the KD-SR versus the DV-SS-Si. Outcome measurements and statistical analysisThe primary endpoint was the success rate of operation. The operation was successful if (1) there was no open or laparoscopic conversion, (2) the warm ischemia time was <30 min for RENAL nephrometry scores of 4–6 or 40 min for RENAL nephrometry scores of 7–9, and (3) the pathological margin was negative. The secondary endpoint was the estimated glomerular filtration rate (eGFR). A threshold of 10% was set to demonstrate noninferiority. Results and limitationsFrom September 2020 to March 2021, 100 participants were enrolled, of whom 99 (49 in the KD-SR group and 50 in the DV-SS-Si group) were finally included in the full analysis set and 98 (49 in the KD-SR group and -49 in the DV-SS-Si group) in the per-protocol set. Baseline demographic and clinical characteristics were similar between the two groups. All surgeries were completed successfully. The eGFR at postoperative weeks 4–12 and adverse events were similar between the two groups. The docking time and suture time per stitch were longer in the KD-SR group. The main limitation was that a negative margin was considered as the primary outcome rather than survival. ConclusionsThe KD-SR achieved noninferior outcomes as compared with the DV-SS-Si regarding safety and efficacy for T1a tumors. Patient summaryThe first trial comparing the KangDuo surgical robot (KD-SR) versus the da Vinci Si Surgical System for robot-assisted partial nephrectomy showed that the KD-SR is a viable option for minimally invasive treatment of T1a renal tumors.

Biportal endoscopic versus microscopic discectomy for lumbar herniated disc: a randomized controlled trial

BACKGROUND CONTEXTBiportal endoscopic discectomy has been frequently performed in recent years and has shown acceptable clinical outcomes. However, evidence regarding its efficacy and safety remains limited. PURPOSEThis study aimed to compare the clinical efficacy and safety of biportal endoscopic with that of open microscopic discectomy in patients with single-level herniated lumbar discs. STUDY DESIGNProspective, randomized, multicenter, open-label, assessor-blind, non-inferiority controlled trial. PATIENT SAMPLESixty-four participants suffering from low back and leg pain with a single-level herniated lumbar disc and required discectomy. OUTCOME MEASURESOutcomes were assessed with the use of patient-reported outcome measures (PROMs), visual analog scale (VAS) pain score for surgical site, low back and lower extremity, Oswestry Disability Index (ODI) for lumbar disabilities, European Quality of Life-5 Dimensions value for quality of life, and painDETECT for neuropathic pain. Surgery-related outcomes such as hospital stay, operation time, and opioid usage were collected. Adverse events occurring during the follow-up period were also noted. METHODSAll participants were randomly assigned in a 1:1 ratio to undergo biportal endoscopic (biportal group) or microscopic discectomy (microscopy group). The primary outcome was the difference in ODI scores at 12-months post surgically based on a modified intention-to-treat strategy, with a non-inferiority margin of 12.8 points. The secondary outcomes included PROMs, surgery-related outcomes, and adverse events. RESULTSThe ODI score at the 12-month follow-up was 11.97 in the microscopy group and 13.89 in the biportal group (mean difference, 1.92; 95% confidence interval [CI], -3.50 to 7.34), showing the non-inferiority of biportal group. The results for the secondary outcomes were similar to those for the primary outcome. Creatinine phosphokinase ratios were low in the biportal group. Early surgical site pain was slightly lower in the biportal group (mean difference of VAS pain score at 48-hr, -0.98; 95% CI, -1.77 to -0.19). Adverse events including reoperation showed no significant difference between the groups. CONCLUSIONBiportal endoscopic discectomy was non-inferior to microscopic discectomy over a 12 month period. Biportal endoscopic discectomy is suggested to be a relatively safe and effective surgical technique with the slight advantage of reduced muscle damage. However, the clinical implications of surgical site pain should be carefully considered.

The Clinical Effectiveness of Blended Cognitive Behavioral Therapy Compared With Face-to-Face Cognitive Behavioral Therapy for Adult Depression: Randomized Controlled Noninferiority Trial

BackgroundInternet-based cognitive behavioral therapy (iCBT) has been demonstrated to be cost- and clinically effective. There is a need, however, for increased therapist contact for some patient groups. Combining iCBT with traditional face-to-face (FtF) consultations in a blended format may produce a new treatment format (B-CBT) with multiple benefits from both traditional CBT and iCBT, such as individual adaptation, lower costs than traditional therapy, wide geographical and temporal availability, and possibly lower threshold to implementation.ObjectiveThe primary aim of this study is to compare directly the clinical effectiveness of B-CBT with FtF-CBT for adult major depressive disorder.MethodsA 2-arm randomized controlled noninferiority trial compared B-CBT for adult depression with treatment as usual (TAU). The trial was researcher blinded (unblinded for participants and clinicians). B-CBT comprised 6 sessions of FtF-CBT alternated with 6-8 web-based CBT self-help modules. TAU comprised 12 sessions of FtF-CBT. All participants were aged 18 or older and met the diagnostic criteria for major depressive disorder and were recruited via a national iCBT clinic. The primary outcome was change in depression severity on the 9-item Patient Health Questionnaire (PHQ-9). Secondary analyses included client satisfaction (8-item Client Satisfaction Questionnaire [CSQ-8]), patient expectancy (Credibility and Expectancy Questionnaire [CEQ]), and working (Working Alliance Inventory [WAI] and Technical Alliance Inventory [TAI]). The primary outcome was analyzed by a mixed effects model including all available data from baseline, weekly measures, 3-, 6, and 12-month follow-up.ResultsA total of 76 individuals were randomized, with 38 allocated to each treatment group. Age ranged from 18 to 71 years (SD 13.96) with 56 (74%) females. Attrition rate was 20% (n=15), which was less in the FtF-CBT group (n=6, 16%) than in the B-CBT group (n=9, 24%). As many as 53 (70%) completed 9 or more sessions almost equally distributed between the groups (nFtF-CBT=27, 71%; nB-CBT=26, 68%). PHQ-9 reduced 11.38 points in the FtF-CBT group and 8.10 in the B-CBT group. At 6 months, the mean difference was a mere 0.17 points. The primary analyses confirmed large and significant within-group reductions in both groups (FtF-CBT: β=–.03; standard error [SE] 0.00; P<.001 and B-CBT: β=–.02; SE 0.00; P<.001). A small but significant interaction effect was observed between groups (β=.01; SE 0.00; P=.03). Employment status influenced the outcome differently between groups, where the B-CBT group was seen to profit more from not being full-time employed than the FtF group.ConclusionsWith large within-group effects in both treatment arms, the study demonstrated feasibility of B-CBT in Denmark. At 6 months’ follow-up, there appeared to be no difference between the 2 treatment formats, with a small but nonsignificant difference at 12 months. The study seems to demonstrate that B-CBT is capable of producing treatment effects that are close to FtF-CBT and that completion rates and satisfaction rates were comparable between groups. However, the study was limited by small sample size and should be interpreted with caution.Trial RegistrationClinicalTrials.gov NCT02796573; https://clinicaltrials.gov/ct2/show/NCT02796573International Registered Report Identifier (IRRID)RR2-10.1186/s12888-016-1140-y