Double-Blind Multicenter Research Articles

Pilot Study of Home-Based Virtual Reality Fitness Training in Post-Discharge Rehabilitation for Patients with Spinal Cord Injury: A Randomized Double-Blind Multicenter Trial.

Spinal cord injury (SCI) patients require continuous rehabilitation post-discharge to ensure optimal recovery. This study investigates the effectiveness of home-based virtual reality fitness training (VRFT) as a convenient and accessible rehabilitation method for SCI patients. This randomized, double-blind, multicenter trial will enroll 120 participants, assigning them to either an 8-week VRFT program (exercise group) or a control group engaging in regular daily activities. The outcomes measured include muscle function, cardiopulmonary fitness, body composition, and physical performance. Our study will determine the safety and feasibility of VRFT in a home setting for SCI patients and evaluate whether these patients can effectively participate in such a program post-discharge. The results of this study are expected to inform future exercise protocols for SCI rehabilitation, offering valuable insights into the utility of VRFT as a therapeutic tool.

N-Acetylcysteine and a Specialized Preventive Intervention for Individuals at High Risk for Psychosis: A Randomized Double-Blind Multicenter Trial.

Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of N-acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients. In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months. While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ± 13.4%, PSM + NAC: 72.7 ± 13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ± 15.3%, PSM + PLC: 39.0 ± 17.4%). However, a log-rank chi-square test in Kaplan-Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281-2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295-2.314). The number of adverse events (AE) did not differ significantly between the four groups. The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.

Efficacy and Safety of Chinese Herbal Medicine in Patients with Acute Intracerebral Hemorrhage: Protocol for a Randomized Placebo-Controlled Double-Blinded Multicenter Trial

Introduction: The popular traditional Chinese medicine (TCM) compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) through effects on brain edema, hematoma absorption, and the immune system. This study is to assess whether FYTF-919 is safe and effective as compared to matching placebo treatment in patients with acute ICH. Methods: The ongoing Chinese Herbal medicine in patients with Acute INtracerebral hemorrhage (CHAIN) is a multicenter, prospective, randomized, double-blind placebo-controlled trial of FYTF-919 in patients with acute ICH at 20–30 hospital sites in China. Eligible ICH patients presenting within 48 h after symptom onset are randomly allocated to receive either FYTF-919 (100 mL per day × 28 d, oral) or matching placebo. A sample size of 1,504 patients is estimated to provide 90% power (α 0.05) to detect a ≥20% improvement in average utility-weight scores on the modified Rankin scale (UW-mRS) assessed at 90 days, with 6% non-adherence and 10% lost to follow-up. The primary efficacy outcome is UW-mRS at 90 days. Secondary outcomes include binary measures of the mRS, neurological impairment on the National Institute of Health Stroke Scale, and health-related quality of life on the EuroQol EQ-5D-5L scale at different time points over 6 months of follow-up. The key safety measure is serious adverse events. Conclusion: CHAIN is on schedule to provide reliable evidence over the benefits of a popular herbal TCM for the treatment of acute ICH.

Randomised Double-blind Placebo-Controlled Multicentre Trial for the Effects of Yokukansan in Smokers with Depressive Tendencies.

Randomised Double-blind Placebo-Controlled Multicentre Trial for the Effects of Yokukansan in Smokers with Depressive Tendencies.

Treatment of Persistent COVID-19 Smell Dysfunction with Olfactory Training, Co-Ultramicronized Palmitoylethanolamide with Luteolin, or Combined Therapy:  Results of Double-Blinded Multicenter Clinical Trial

Treatment of Persistent COVID-19 Smell Dysfunction with Olfactory Training, Co-Ultramicronized Palmitoylethanolamide with Luteolin, or Combined Therapy:  Results of Double-Blinded Multicenter Clinical Trial

Mucosal Healing Effectiveness and Safety of Anaprazole, a Novel PPI, vs. Rabeprazole in Patients With Duodenal Ulcers: A Randomized Double-Blinded Multicenter Phase II Clinical Trial.

Background: Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs have shown great efficacy, many scientists are still devoted to developing more effective PPIs with better safety profile. Herein, we aimed to compare the safety and efficacy of anaprazole in duodenal mucosal healing, a novel PPI, to that of rabeprazole.Methods: In this multicenter, randomized, positive-controlled, double-blinded, parallel-group phase II clinical trial, a total of 150 qualified patients with endoscopically confirmed active duodenal ulcers were randomized (1:1:1) to receive rabeprazole 10 mg, anaprazole 20 mg or anaprazole 40 mg for 4 weeks. The ulcer healing rates after 4 weeks of treatment were compared between groups by independent central review and investigator review. In addition, symptoms and safety were evaluated.Results: Based on the independent central review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole and 40 mg anaprazole groups were 88.0, 85.1, and 87.5%, respectively, in the FAS population and 88.9, 86.0, and 90.9%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is −2.9% (95% CI, −16.5–10.7%), and −0.5% (95% CI, −13.5–12.5%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Based on the investigator review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole, and 40 mg anaprazole groups were 72.0, 70.2, and 77.1%, respectively, in the FAS population and 75.6, 72.1, and 79.5%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is −1.8% (95% CI, −19.8–16.3%), and 5.1% (95% CI, −12.2–22.3%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Most patients (>90%) eventually achieved complete symptom relief. The incidence rates of adverse events were of no significant differences among the treatment groups. Potential possible better liver tolerance was observed in two anaprazole dose groups than rabeprazole 10 mg group.Conclusion: Both at a dosage of 20 and 40 mg daily, anaprazole, is effective with good safety profile in the treatment of active duodenal ulcers in this Phase 2 study, which allows anaprazole to be advanced to a phase III clinical trial.Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04503629&cntry=&state=&city=&dist=, Identifier: CTR20181464, NCT04503629.

The SNAP Trial: 2-Year Results of a Double-Blind Multicenter Randomized Controlled Trial of a Silicon Nitride Versus a PEEK Cage in Patients After Lumbar Fusion Surgery.

Study Design:Randomized controlled trial.Objectives:Lumbar interbody fusion with cages is performed to provide vertebral stability, restore alignment, and maintain disc and foraminal height. Polyetheretherketone (PEEK) is commonly used. Silicon nitride (Si3N4) is an alternative material with good osteointegrative properties. This study was designed to assess if Si3N4 cages perform similar to PEEK.Methods:A non-inferiority double-blind multicenter RCT was designed. Patients presenting with chronic low-back pain with or without leg pain were included. Single- or double-level instrumented transforaminal lumbar interbody fusion (TLIF) using an oblique PEEK or Si3N4 cage was performed. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ). The non-inferiority margin for the RMDQ was 2.6 points on a scale of 24. Secondary outcomes included the Oswestry Disability Questionnaire (ODI), Visual Analogue Scales (VAS), SF-36 Physical Function, patient and surgeon Likert scores, radiographic evaluations for subsidence, segmental motion, and fusion. Follow-up was planned at 3, 6, 12, and 24-months.Results:Ninety-two patients were randomized (i.e. 48 to PEEK and 44 to Si3N4). Both groups showed good clinical improvements on the RMDQ scores of up to 5-8 points during follow-up. No statistically significant differences were observed in clinical and radiographic outcomes. Mean operative time and blood loss were statistically significantly higher for the Si3N4 cohort. Although not statistically significant, there was a higher incidence of complications and revisions associated with the Si3N4 cage.Conclusions:There was insufficient evidence to conclude that Si3N4 was non-inferior to PEEK.

Impact of rosuvastatin on atherosclerosis in people with HIV at moderate cardiovascular risk: a randomised, controlled trial.

People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease. This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population. A double-blind multicentre, randomised, placebo-controlled trial was performed. Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10-15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 : 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid--intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov: NCT01813357). Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011]. In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.

KL 37 Statins for prevention of pre-eclampsia

Pre-eclampsia is associated with serious maternal and perinatal morbidity and in low resource nations accounts for over 20% of all maternal and perinatal mortality. An effective prophylaxis or targeted therapy against pre-eclampsia is desperately needed. Statins inhibit sFlt-1 secretion from endothelial and trophoblast cells in vitro and increase PlGF levels in vivo. Statins may therefore offer a targeted and non-invasive prophylaxis against pre-eclampsia. Previously however, statins taken during pregnancy, especially lipophilic statins that cross plasma membranes, have been linked with major congenital malformations. After adjustment for underlying maternal diabetes however, a large subsequent registry showed no such association between first trimester statin use and congenital anomalies. Nevertheless, uncertainty remains about the safety of statins used after the first trimester on long-term childhood development. We investigated whether statins might offer a potential therapy for pre-eclampsia by conducting the StAmP trial, Statins to Ameliorate Pre-Eclampsia. This double blind multicenter, placebo-controlled randomized trial assessed the effect of a hydrophilic statin Pravastatin on s-FLT1 levels in women with early onset pre-eclampsia. The preliminary results of Stamp and other reports of statins to ameliorate pre-eclampsia will be discussed.

A Prospective, Randomized, Double-Blind Multicenter Study Comparing Continuous Diffusion of Oxygen Therapy to Sham Therapy in the Treatment of Diabetic Foot Ulcers.

Background:Over the past generation, preclinical data have suggested that there is a potential physiologic benefit to applying oxygen topically to wounds. However, we are unaware of any studies in the literature that have robustly assessed whether this would lead to a higher proportion of healing in similarly treated people without oxygen. Therefore, the purpose of this study was to assess this in people being treated for chronic diabetic foot ulcers (DFUs).Methods:We enrolled and randomized 100 subjects with DFUs (79% male, aged 58.3 ± 12.1 years) to receive either active continuous diffusion of oxygen (CDO) therapy using an active CDO device, or an otherwise fully operational sham device that provided moist wound therapy (MWT) without delivering oxygen. Patients were followed until closure or 12 weeks, whichever was sooner. Patients, treating physicians and independent evaluators were blinded to the study arm. All patients received identical offloading, dressings and follow-up.Results:There were no significant differences in assessed descriptive characteristics between the treatment arms (P > .05 for all). A significantly higher proportion of people healed in the active arm compared to sham (46% vs 22%, P = .02). This relative effect became greater in more chronic wounds (42.5% vs 13.5%, P = .006). Patients randomized to the active device experienced significantly faster rates of closure relative to the sham (P < .001).Conclusions:The results of this study suggest that continuously diffused oxygen over a wound leads to significantly higher rates of closure, and faster time to closure, compared to similarly treated patients receiving standard therapy coupled with a sham device. Furthermore, the relative efficacy appears to improve the more the therapy may be needed (more chronic and larger wounds).

SUN-LB280: Double Blind Multicenter Phase III Gortec Trial Evaluating the Efficacy of Oral Immune Modulating Formulae Therapy During Adjuvant Chemoradiotherapy in Head and Neck Squamous Cell Carcinoma (HNSCC)

SUN-LB280: Double Blind Multicenter Phase III Gortec Trial Evaluating the Efficacy of Oral Immune Modulating Formulae Therapy During Adjuvant Chemoradiotherapy in Head and Neck Squamous Cell Carcinoma (HNSCC)

Re: Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE)

Re: Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE)

Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE)

BackgroundIncontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy. ObjectiveTo evaluate the efficacy and the safety and tolerability of combination (solifenacin 5mg and mirabegron 50mg) versus solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of solifenacin 5mg. Design, setting, and participantsOAB patients remaining incontinent despite daily solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25mg increasing to 50mg after week 4. Outcome measurements and statistical analysisThe primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (solifenacin plus mirabegron) with one treatment alone (solifenacin) tested the superiority of combination versus solifenacin 5mg, noninferiority (and potential superiority) of combination versus solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus solifenacin monotherapy. Results and limitationsA total of 2174 patients were randomised to combination (n=727), solifenacin 5mg (n=728), or solifenacin 10mg (n=719). At EOT, combination was superior to solifenacin 5mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001), and incontinence noted in a 3-d diary (p=0.014). Combination was noninferior to solifenacin 10mg for key secondary end points and superior to solifenacin 10mg for improving daily micturitions. All treatments were well tolerated. ConclusionsAdding mirabegron 50mg to solifenacin 5mg further improved OAB symptoms versus solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5mg. Patient summaryIn this 12-wk study, overactive bladder patients who remained incontinent despite initial solifenacin 5mg treatment received additional treatment with mirabegron 50mg. Combining mirabegron 50mg with solifenacin 5mg was superior to solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated. Trial registrationClinicalTrials.gov NCT01908829.

Tolerability and Feasibility of Beta-Blocker Titration in HFpEF Versus HFrEF: Insights From the CIBIS-ELD Trial

ObjectivesThis study evaluated the tolerability and feasibility of titration of 2 distinctly acting beta-blockers (BB) in elderly heart failure patients with preserved (HFpEF) and reduced (HFrEF) left ventricular ejection fraction. BackgroundBroad evidence supports the use of BB in HFrEF, whereas the evidence for beta blockade in HFpEF is uncertain. MethodsIn the CIBIS-ELD (Cardiac Insufficiency Bisoprolol Study in Elderly) trial, patients >65 years of age with HFrEF (n = 626) or HFpEF (n = 250) were randomized to bisoprolol or carvedilol. Both BB were up-titrated to the target or maximum tolerated dose. Follow-up was performed after 12 weeks. HFrEF and HFpEF patients were compared regarding tolerability and clinical effects (heart rate, blood pressure, systolic and diastolic functions, New York Heart Association functional class, 6-minute-walk distance, quality of life, and N-terminal pro–B-type natriuretic peptide). ResultsFor both of the BBs, tolerability and daily dose at 12 weeks were similar. HFpEF patients demonstrated higher rates of dose escalation delays and treatment-related side effects. Similar HR reductions were observed in both groups (HFpEF: 6.6 beats/min; HFrEF: 6.9 beats/min, p = NS), whereas greater improvement in NYHA functional class was observed in HFrEF (HFpEF: 23% vs. HFrEF: 34%, p < 0.001). Mean E/e′ and left atrial volume index did not change in either group, although E/A increased in HFpEF. ConclusionsBB tolerability was comparable between HFrEF and HFpEF. Relevant reductions of HR and blood pressure occurred in both groups. However, only HFrEF patients experienced considerable improvements in clinical parameters and left ventricular function. Interestingly, beta-blockade had no effect on established and prognostic markers of diastolic function in either group. Long-term studies using modern diagnostic criteria for HFpEF are urgently needed to establish whether BB therapy exerts significant clinical benefit in HFpEF. (Comparison of Bisoprolol and Carvedilol in Elderly Heart Failure [HF] Patients: A Randomised, Double-Blind Multicentre Study [CIBIS-ELD]; ISRCTN34827306)

6% Hydroxyethyl Starch (130/0.4) vs. Ringer’s Lactate Before Spinal Anaesthesia for Caesarean Delivery; The Randomized Double-blind Multicentre CAESAR Trial

Mercier, F. J.*; Diemunsch, P.†; Duclay-Bouthors, A. S.‡; Mignon, A.§; Fischler, M.∥; Malinovsky, J. M.¶; Bolandard, F.#; Aya, A. G.**; Raucoules-Aimé, M.††; Chassard, D.‡‡; Keita, H.§§; Rigouzza, A.∥∥; Le Gouez, A.* Author Information

P16 Methylation as an Early Predictor for Cancer Development From Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study

BackgroundSilencing of P16 through methylation and locus deletion is the most frequent early events in carcinogenesis. The aim of this study is to prospectively determine if early P16 methylation is a predictor for oral cancer development. MethodsPatients (n=181) with mild or moderate oral epithelial dysplasia (OED) were recruited into the double blind multicentre cohort. P16 methylation was analyzed using the MethyLight assay. Progression of OEDs was monitored for a minimum 3year follow-up period. FindingsP16 methylation-informative cases (n=152) were enrolled in the prospective multicenter cohorts with an ultimate compliance of 96.7%. OED-derived squamous cell carcinomas were observed in 21 patients (14.3%) during the follow-up (median, 41.0months). The cancer progression rate from the P16 methylation-positive patients was significantly increased when compared to P16 methylation-negative patients [27.1% vs 8.1%; adjusted odds ratio=4.6; P=0.006]. When the P16 methylation-positive criteria were used as a biomarker for early prediction of cancer development from OEDs, sensitivity and specificity of 62% and 76% were obtained, respectively. InterpretationP16 methylation is unequivocally a marker for determining the malignant potential of OED and there is no need for further research regarding this aspect. FundingNational Basic Research Programs of China (2011CB504201 and 2015CB553902), Beijing Science and Technology Commission (Z090507017709016), and Beijing Municipal Administration of Hospital (XM201303) to Dajun Deng. The funding agencies have no role in the actual experimental design, patient recruitment, data collection, analysis, interpretation, or writing of this manuscript.

Early report of a randomized comparative clinical trial of Strattice™ reconstructive tissue matrix to lightweight synthetic mesh in the repair of inguinal hernias

Biologic grafts are rarely used for inguinal herniorrhaphy. The aim of this study was to compare the clinical outcomes between patients undergoing a Lichtenstein's hernioplasty with a porcine mesh versus a standard synthetic. A prospective, randomized, double-blinded multicenter, evaluation of inguinal hernia repair was conducted between 2008 and 2010. Lichtenstein hernioplasty was performed using Strattice™ or lightweight polypropylene (Ultrapro) mesh. Quality of life, pain, overall complication rate, and recurrence were measured. One hundred and seventy-two patients were randomized to Strattice™ (n = 84) or Ultrapro (n = 88). At 3 months postoperatively, there were no differences on the occurrence or type of wound events [RR: 0.98 (95% CI 0.52-1.86, p = 0.69), Strattice™ (15 events) vs. Ultrapro (16 events)]. The mean level of impairment caused by the hernia, assessed by Activities Assessment Scale (AAS), significantly decreased postoperatively in both groups at 3 months (31% Strattice™ and 37% Ultrapro). Patients in the Strattice group reported significantly less postoperative pain during postoperative days 1 through 3 compared to Ultrapro patients. However, the amount of postoperative pain at 3 months, as assessed by the mean worst pain score on a visual analog scale and the Brief Pain Index, was similar between groups (95% CI 1.0-29.3). No hernia recurrences were observed in either group. Strattice™ is safe and effective in repairing inguinal hernia, with comparable intra-operative and early postoperative morbidity to synthetic mesh. Long-term follow-up is necessary in order to know whether the clinical outcomes of Strattice are equivalent to standard synthetic mesh in patients undergoing Lichtenstein's hernioplasty.

Nitrous Oxide for Early Analgesia in the Emergency Setting: A Randomized, Double‐blind Multicenter Prehospital Trial

Although 50% nitrous oxide (N(2) O) and oxygen is a widely used treatment, its efficacy had never been evaluated in the prehospital setting. The objective of this study was to demonstrate the efficacy of premixed N(2) O and oxygen in patients with out-of-hospital moderate traumatic acute pain. This prospective, randomized, multicenter, double-blind trial enrolled patients with acute moderate pain (numeric rating scale [NRS] score between 4 and 6 out of 10) caused by trauma. Patients were assigned to receive either 50/50 N(2) O and oxygen 9 L/min (N(2) O group) or medical air (MA) 9 L/min (MA group), in ambulances from two nurse-staffed fire department centers. After the first 15 minutes, every patient received N(2) O and oxygen. The primary endpoint was pain relief at 15 minutes (T15), defined as a NRS ≤ 3 of 10. The NRS was measured every 5 minutes. Secondary endpoints were treatment safety and adverse events, time to analgesia, and patient and investigator satisfaction with analgesia. Sixty patients were included with no differences between groups in age (median = 34 years, interquartile range [IQR] = 23 to 53 years), sex (37 males, 66%), and initial median NRS of 6 (IQR = 5 to 6). At T15, 67% of the patients in the N(2) O group had an NRS score of 3 or lower versus 27% of those in the MA group (delta = 40%, 95% confidence interval [CI] = 17% to 63%; p < 0.001). The median pain scores were lower in the N(2) O group at T15, 2 (IQR = 1 to 4) versus 5 (IQR = 3 to 6). There was a difference at 5 minutes that persisted at all subsequent time points. Four patients (one in the N(2) O group) experienced adverse events (nausea) during the protocol. This study demonstrates the efficacy of N(2) O for the treatment of pain from acute trauma in adults in the prehospital setting.

Abstract 176: A Randomized, Double-Blind Multicenter Trial Comparing Vasopressin and Adrenaline in Patients with Cardiac Arrest at the Emergency Department (Preadmission Intravenous Vasopressin, Adrenaline Outcome Trial [PIVOT

Aims Recently, vasopressin has been used in cardiac arrest patients. In human studies on vasopressin, clinical trials have produced conflicting results. We aimed to compare vasopressin and adrenaline in the treatment of cardiac arrest at the Emergency Department (ED). Methods This was a randomised, double-blind, multi-centre, parallel-design clinical trial involving four hospitals. All cardiac arrest patients (confirmed by the absence of pulse, unresponsiveness and apnea) aged above 16 were eligible (age 21 and above for one hospital). The exclusion criteria were traumatic cardiac arrest or contraindicated cardio-pulmonary resuscitation (CPR). Eligible patients were randomly assigned to receive adrenaline (1 mg) or vasopressin (40 IU) in the ED. The primary outcome was survival to hospital discharge (defined as patient discharged alive or survival to 30 days post arrest). Results We recruited 727 eligible patients (adrenaline= 353; vasopressin= 374) whose baseline characteristics in both groups were comparable. After adjustment for race, medical history, bystander CPR and prior adrenaline given, more patients survived to hospital admission with vasopressin (22•2%) than adrenaline (16•7%) (p=0•047, RR=1•43, 95% CI=1•02- 2•04). No significant differences were noted for return of spontaneous circulation. Eight patients (2•3%) from the adrenaline and 11 (2•9%) from the vasopressin group survived to hospital discharge. After adjusting for race, medical history, bystander CPR and previous adrenaline given, there was no significant difference (p=0•274, RR= 1•72, 95% CI=0•65 -4•51). Post hoc analysis suggested improved outcomes for vasopressin in patients with prolonged arrest times. Conclusion Vasopressin seems to improve survival to admission in patients with prolonged cardiac arrest but not long term survival. Further studies on the effect of vasopressin on patients with prolonged arrest are needed. (ClinicalTrials.gov number, NCT00358579 )

Efficacy evaluation of highly purified intra-articular hyaluronic acid (Sinovial ®) vs hylan G-F20 (Synvisc ®) in the treatment of symptomatic knee osteoarthritis. A double-blind, controlled, randomized, parallel-group non-inferiority study

Knee osteoarthritis is a major cause of disability and pain. This phase III, double-blind (patient and observer blinded,) multicenter, randomized, non-inferiority study was conducted to demonstrate the non-inferiority of the highly purified intra-articular injection of hyaluronic acid (Sinovial(®)) in comparison to Hylan G-F20 (Synvisc(®)) in the treatment of knee osteoarthritis. A total of 381 patients were randomly assigned to receive either the test drug, 16 mg/2 ml (0.8%) highly purified ia hyaluronic acid of biofermentative origin (Sinovial(®)), or the comparative drug, 16 mg/2 ml of 0.8% hylan G-F20 (Synvisc(®)). The duration of the treatment was 2 weeks (three injections at 1-week interval), followed by an observation period of 6 months. The primary efficacy variable was the improvement in mean Western Ontario and McMaster Universities (WOMAC) pain subscore from baseline to the final visit (week 26), compared between the two treatment groups. The acceptable margin for non-inferiority was chosen to be 8 mm. At week 26, WOMAC pain subscores decreased by a mean of 32.5 for both Sinovial(®) and Synvisc(®). These results met prespecified criteria for non-inferiority for both the Intent-to-Treat and Per-Protocol populations. There were no statistically significant differences between groups at 26 weeks, although Sinovial(®)-treated patients tended to have a slightly better outcome for select variables, as they did at earlier time-points, some of which reached statistical significance. Both hyaluronic acid preparations were well-tolerated, with no statistically significant differences in tolerability profile between groups. Sinovial(®) and Synvisc(®) treatments were found to be equivalent, both in terms of efficacy and safety. NCT00556608 (ClinicalTrials.gov Identifier).