Versus Placebo Research Articles

Effect of Intravenous Tirofiban Versus Placebo on First-Pass Successful Reperfusion in Endovascular Stroke Thrombectomy: Insights From the RESCUE BT Randomized Clinical Trial.

First-pass successful reperfusion (FPSR), defined as a successful/complete reperfusion achieved after a single thrombectomy pass, is predictive of favorable outcome in patients with acute ischemic stroke with large-vessel occlusion. It is unknown whether intravenous tirofiban is effective in increasing the rate of FPSR in acute anterior large-vessel occlusion stroke. Patients who had acute large-vessel occlusion stroke presenting within 24 hours and underwent endovascular thrombectomy were analyzed from the RESCUE BT (Intravenous Tirofiban for Patients With Large Vessel Occlusion Stroke) clinical trial, of which the main analysis was neutral. The RESCUE BT trial randomized patients to receive either intravenous tirofiban or placebo before endovascular thrombectomy. The primary end point was FPSR, defined as successful reperfusion (extended thrombolysis in cerebral infarction scale 2b50, 2c, or 3) at first thrombectomy attempt. A modified Poisson regression analysis assessed the association between intravenous tirofiban treatment and FPSR. Of 948 enrolled patients, 463 patients were randomized to the tirofiban group and 485 to the placebo group. The mean age was 67 years, and 41.0% of the patients were women. FPSR was achieved more often in the tirofiban group (30.5% versus 23.5%; adjusted risk ratio, 1.24 [95% CI, 1.01-1.51]; P=0.04). FPSR was associated with a favorable shift to lower modified Rankin Scale disability levels at 90 days (common odds ratio, 1.42 [95% CI, 1.08-1.86]; P=0.01). In this post hoc analysis of the RESCUE BT trial, treatment with intravenous tirofiban before endovascular thrombectomy was associated with increased FPSR in patients with acute ischemic stroke due to large-vessel occlusion in the anterior circulation. FPSR was associated with reduced 90-day levels of disability. URL: http://chictr.org; Unique Identifier: ChiCTR-INR-17014167.

Diabetes Risk Factors in People With HIV Receiving Pitavastatin Versus Placebo for Cardiovascular Disease Prevention : A Randomized Trial.

REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) led to new guidelines for statin use among people with HIV (PWH) with low to moderate risk for atherosclerotic cardiovascular disease (ASCVD). Little is known about the natural history of diabetes mellitus (DM) or mechanisms contributing to statin effects on DM among this population. To determine the contribution of known DM risk factors to excess risk for DM with pitavastatin in REPRIEVE. Phase 3, primary ASCVD prevention trial over a median of 5.6 years of follow-up. (ClinicalTrials.gov: NCT02344290). Global, multicenter trial. 7731 PWH aged 40 to 75 years with low to moderate ASCVD risk (by the pooled cohort equations from the American College of Cardiology and American Heart Association) without DM at study entry. Random 1:1 assignment to pitavastatin, 4 mg daily, or placebo. New-onset DM was determined at each visit by clinical diagnosis requiring initiation of medication treatment for DM. The incidence of new-onset DM was assessed in relation to predefined demographic and metabolic risk factors, stratified by treatment group. Treatment effects of pitavastatin on progression to new DM in key subgroups were determined. Participants with at least 3 DM risk factors (vs. no risk factors) had increased risk for DM in each treatment group (incidence rate, 3.24 per 100 person-years [PY] vs. 0.34 per 100 PY [pitavastatin] and 2.66 per 100 PY vs. 0.27 per 100 PY [placebo]). The incidence of DM was highest in South Asia. In adjusted analyses, high body mass index, prediabetes, and metabolic syndrome components were strongly associated with new-onset DM (all P < 0.005). Pitavastatin was the only statin assessed; DM was assessed clinically. Metabolic risk factors, including prediabetes and obesity, contributed to new-onset DM in statin- and placebo-treated participants. A clinically significant effect of pitavastatin on DM was seen primarily among those with multiple risk factors for DM at entry. Strategies targeting key metabolic risk factors, like obesity and prediabetes, may help protect against DM among PWH. National Heart, Lung, and Blood Institute of the National Institutes of Health.

A Multi-Hospital Comparative Study on the Efficacy of Probiotics Versus Placebo in Preventing Antibiotic-Associated Diarrhea in Adult Patients.

Antibiotic-associated diarrhea (AAD) is a prevalent complication of antibiotic therapy, attributed to disruptions in gut microbiota. Probiotics are increasingly studied for their potential in preventing AAD by restoring microbial balance. The aim of this investigation was to assess the efficacy of probiotics in reducing AAD in adult patients when compared to a placebo. This research was conducted from March 2023 to March 2024 using a randomized, placebo-controlled design at multiple institutions: Khyber Teaching Hospital, Peshawar; Prime Teaching Hospital, Peshawar; Mufti Mahmood Memorial Teaching Hospital, Dera Ismail Khan; Shalamar Hospital, Lahore; University Hospitals of Leicester; and DHQ Teaching Hospital Kohat, enrolling 340 adult patients prescribed systemic antibiotics. Eligible participants were aged 18 years and older, while those with chronic diarrhea, inflammatory bowel disease, immunodeficiency, recent probiotic or antibiotic use, or inability to provide informed consent were excluded. The sample size was calculated using WHO guidelines, resulting in a target of 340 to ensure adequate power. Participants were randomized to receive either probiotics (Lactobacillus rhamnosus GG and Bifidobacterium longum BB536) or placebo, administered within 24 hours of starting antibiotics. Daily monitoring of bowel habits and symptoms was performed using standardized diaries, and adherence was evaluated through pill counts. Statistical analyses were performed using IBMSPSSStatistics for Windows, Version 27 (Released 2020; IBM Corp., Armonk, New York, United States), comparing the incidence, severity, and duration of AADbetween groups, with a significance threshold of p < 0.05. In the probiotic group, 31 patients (18.23%) developed AAD compared to 53 patients (31.17%) in the placebo group (p=0.01). Among those with AAD, the probiotic group experienced a shorter duration (mean 3.5 ± 1.2 days) compared to placebo (mean 5.1 ± 1.8 days, p=0.002). Adherence rates were high in both groups (probiotic: 96.4%, placebo: 95.9%). Significant improvements in bowel habits were reported more frequently in the probiotic group (77.06%) than placebo (50.59%, p=0.02). The hospital stay duration was similar between groups (probiotic: mean 7.8 ± 2.1 days, placebo: mean 8.3 ± 2.4 days, p=0.15). Probiotics significantly reduced the incidence and duration of AAD compared to placebo, with high adherence and favorable patient-reported outcomes.

Once Daily Oral Relugolix Combination Therapy Versus Placebo in Patients With Endometriosis-Associated Pain: Two Replicate Phase 3, Randomised, Double-Blind, Studies (SPIRIT 1 and 2)

The author describes the results of a study to examine the effect of three treatment regimens on pain associated with endometriosis.

Caffeine Gum Improves Reaction Time but Reduces Composure Versus Placebo During the Extra-Time Period of Simulated Soccer Match-Play in Male Semiprofessional Players.

This study aimed to determine whether caffeine gum influenced perceptual-cognitive and physical performance during the extra-time period of simulated soccer match-play. Semiprofessional male soccer players (n = 12, age: 22 ± 3years, stature: 1.78 ± 0.06m, mass: 75 ± 9kg) performed 120-min soccer-specific exercise on two occasions. In a triple-blind, randomized, crossover design, players chewed caffeinated (200mg; caffeine) or control (0mg; placebo) gum for 5min following 90min of soccer-specific exercise. Perceptual-cognitive skills (i.e.,passing accuracy, reaction time, composure, and adaptability) were assessed using a soccer-specific virtual reality simulator, collected pre- and posttrial. Neuromuscular performance (reactive-strength index, vertical jump height, absolute and relative peak power output, and negative vertical displacement) and sprint performance (15 and 30m) were measured at pretrial, half-time, 90min, and posttrial. Caffeine gum attenuated declines in reaction time (pre: 90.8 ± 0.8AU to post: 90.7 ± 0.8AU) by a further 4.2% than placebo (pre: 92.1 ± 0.8AU to post: 88.2 ± 0.8AU; p < .01). Caffeine gum reduced composure by 4.7% (pre: 69.1 ± 0.8AU to post: 65.9 ± 0.8AU) versus placebo (pre: 68.8 ± 0.8AU to post: 68.3 ± 0.8AU; p < .01). Caffeine gum did not influence any other variables (p > .05). Where caffeine gum is consumed by players prior to extra-time, reaction time increases but composure may be compromised, and neuromuscular and sprint performance remain unchanged. Future work should assess caffeine gum mixes with substances like L-theanine that promote a relaxed state under stressful conditions.

53808 Adjuvant Pembrolizumab Versus Placebo in Stage IIB or IIC Melanoma: Exploratory Post Hoc Analyses of Patients with New Primary Melanoma and Other Skin Cancers from the Phase 3 KEYNOTE-716 Study

53808 Adjuvant Pembrolizumab Versus Placebo in Stage IIB or IIC Melanoma: Exploratory Post Hoc Analyses of Patients with New Primary Melanoma and Other Skin Cancers from the Phase 3 KEYNOTE-716 Study

Update on APPEAL, an International Randomized Controlled Trial Evaluating Ciprofloxacin Versus Placebo in Patients Undergoing Shockwave Lithotripsy for Urolithiasis

The blinded APPEAL trial is assessing the effectiveness of antimicrobial prophylaxis in preventing infections after shockwave lithotripsy for urinary stones. This large, pragmatic, international trial will provide trustworthy evidence to inform guidelines and influence global practices.

Effect of Vitamin D Versus Placebo on Fetal Outcomes and Maternal Control in Pregnant Women with pre Gestational Diabetes Mellitus

Effect of Vitamin D Versus Placebo on Fetal Outcomes and Maternal Control in Pregnant Women with pre Gestational Diabetes Mellitus

Comparison of Outcomes of Intravenous Dexamethasone Versus Placebo as Adjunct to Local Anaesthetic Brachial Plexus Block for Upper Limb Surgery

Introduction: Dexamethasone has been tested in combination with different local anesthetics with varying degree of results including increase in intensity and duration of block. Objectives: To compare the outcomes of intravenous dexamethasone versus placebo as adjunct to local anesthetic brachial plexus block for upper limb surgery. Study design: Randomized controlled trial Setting: Department of Anesthesia, pain management and intensive care Holy Family Hospital, Rawalpindi. Study duration: 7th November 2019 till 6th May 2020. Materials &amp; Methods: A total of 10 0 patients of either gender aged 18 to 60 years admitted for upper limb surgery were included. Patients with pregnancy, DM, block failure and contraindication to brachial plexus block were excluded. Patients in group A received a block injection with 30ml of 0.5% bupivacaine along with 2ml of intravenous dexamethasone. Group B patients received 30ml of 0.5% bupivacaine for block injection and 2ml of normal saline intravenously. Block success was confirmed using the sensory and motor examination of the upper limb. Block duration was recorded in hours, opioid consumption was recorded in intravenous morphine equivalents in first 24 hours, visual analogue scores for pain on scale of 0-10 at upper limb at rest was recorded at 8 and 24 hours. Results: In our study, duration of local anesthetic brachial plexus block in dexamethasone and placebo group were 16.12 ± 1.33 hrs and 9.77 ± 1.26 hrs respectively with p-value = 0.0001. Opioid consumption in Morphine Equivalents at 24 hrs in local anesthetic brachial plexus block and placebo group were 16.48 ± 2.60 vs 22.68 ± 3.78 with p-value &lt; 0.0001 respectively. Conclusion: This study concluded that intravenous dexamethasone has better outcomes as compared to intravenous saline as adjunct to local anesthetic brachial plexus block for upper limb surgery.

Efficacy of pharmacologic interventions on magnetic resonance imaging biomarkers in patients with nonalcoholic fatty liver disease: systematic review and network meta-analysis.

Several agents are under investigation for nonalcoholic fatty liver disease (NAFLD). We assessed the comparative efficacy of pharmacologic interventions for patients with NAFLD focusing on magnetic resonance imaging (MRI) biomarkers. We searched Medline, Embase, and CENTRAL. We included randomized controlled trials of more than 12weeks of intervention that recruited patients with biopsy-confirmed or MRI-confirmed NAFLD and assessed the efficacy of interventions on liver fat content (LFC) and fibrosis by means of MRI. We performed random-effects frequentist network meta-analyses and assessed confidence in our estimates using the CINeMA (Confidence in Network Meta-Analysis) approach. We included 47 trials (8583 patients). Versus placebo, thiazolidinediones were the most efficacious for the absolute change in LFC, followed by vitamin E, fibroblast growth factor (FGF) analogs, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with mean differences ranging from -7.46% (95% confidence interval [-11.0, -3.9]) to -4.36% (-7.2, -1.5). No differences between drug classes were evident. Patients receiving GLP-1 RAs or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs were more likely to achieve ≥30% relative reduction in LFC. Among agents, efruxifermin produced the largest reduction in LFC compared to placebo [-13.5% (-18.5, -8.5)], followed by pioglitazone, while being superior to most interventions. The effect of interventions on magnetic resonance elastography assessed fibrosis was small and insignificant. The confidence in our estimates was low to very low. Several drug classes may reduce LFC in patients with NAFLD without a significant effect on fibrosis; nevertheless, trial duration was small, and confidence in the effect estimates was low.

Comparative Meta-Analysis of Retatrutide Versus Placebo and Dulaglutide for Weight Loss and Diabetes Management: Insights From Clinical Trials.

Comparative Meta-Analysis of Retatrutide Versus Placebo and Dulaglutide for Weight Loss and Diabetes Management: Insights From Clinical Trials.

Early Vaginal Progesterone Versus Placebo in Twin Pregnancies for Prevention of Spontaneous Pre-Term Birth

Early Vaginal Progesterone Versus Placebo in Twin Pregnancies for Prevention of Spontaneous Pre-Term Birth

Efficacy of Epsilon Aminocaproic Acid Versus Placebo in Coronary Artery Bypass Graft: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Efficacy of Epsilon Aminocaproic Acid Versus Placebo in Coronary Artery Bypass Graft: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Resting-State Brain Functional Connectivity Predictors of Differential Improvement in Irritability With Sertraline Versus Placebo: Findings From the EMBARC Study

Resting-State Brain Functional Connectivity Predictors of Differential Improvement in Irritability With Sertraline Versus Placebo: Findings From the EMBARC Study

Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial

BackgroundPulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC). However, it is unknown if PH-specific therapy is beneficial in SSc patients with mildly elevated pressure (SSc-MEP, mPAP 21–24 mmHg).MethodsThe SEPVADIS trial is a randomized, double-blind, placebo-controlled phase 2 trial of sildenafil in SSc-MEP patients with a target enrollment of 30 patients from two academic sites in the United States. The primary outcome is change in six-minute walk distance after 16 weeks of treatment. Secondary endpoints include change in pulmonary arterial compliance by RHC and right ventricular function by cardiac magnetic resonance imaging at 16 weeks. Echocardiography, serum N-terminal probrain natriuretic peptide, and health-related quality of life is being measured at 16 and 52 weeks.DiscussionThe SEPVADIS trial will be the first randomized study of sildenafil in SSc-MEP patients. The results of this trial will be used to inform a phase 3 study to investigate the efficacy of treating patients with mild elevations in mPAP.Trial registrationClinicalTrials.gov Identifier NCT04797286.

Long-term Comparative Efficacy of Inebilizumab in the AQP4+ Subpopulation from N-MOmentum Open-label Period Versus Azathioprine and Immunosuppressants and Versus Placebo in Patients with NMOSD (S32.001)

Long-term Comparative Efficacy of Inebilizumab in the AQP4+ Subpopulation from N-MOmentum Open-label Period Versus Azathioprine and Immunosuppressants and Versus Placebo in Patients with NMOSD (S32.001)

Effect of High-Dose Subcutaneous Spesolimab on Skin Manifestations: Results from the Pivotal Effisayil 2 Trial of Flare Prevention in Generalized Pustular Psoriasis

Introduction &amp; Objectives: Generalized pustular psoriasis (GPP) is a chronic, rare and potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is an effective and approved treatment for GPP flares in adults. Effisayil 2 (NCT04399837) was a pivotal, randomized controlled trial that evaluated the efficacy and safety of subcutaneous spesolimab in preventing GPP flares. Here, we report the effect of high-dose spesolimab versus placebo on GPP lesions.&#x0D; Materials &amp; Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to receive one of three subcutaneous spesolimab regimens or placebo for 48 weeks. High-dose spesolimab regimen was loading dose 600 mg, followed by maintenance dose 300 mg every 4 weeks. GPP Physician Global Assessment (GPPGA) subscores for erythema, pustules and scaling/crusting, and total score were compared between high-dose spesolimab and placebo groups at baseline and over the treatment period (scale: 0, clear to 4, severe).&#x0D; Results: Proportion of patients with baseline score of 0 for each GPPGA subscore and total score was generally similar between treatment groups, except erythema; (high-dose spesolimab [n=30] vs placebo [n=31]: erythema, 13.3% vs 22.6%; pustules, 66.7% vs 67.7%; scaling/crusting, 23.3% vs 22.6%; total score, 10.0% vs 12.9%). By Week 4, proportion of patients with scores of 0 increased with high-dose spesolimab versus placebo, (erythema, 33.3% vs 19.4%; pustules, 80.0% vs 41.9%; scaling/crusting, 30.0% vs 19.4%; total score, 26.7% vs 16.1%), and high-dose spesolimab group had fewer flares (10.0% vs 35.5%). This trend was maintained at Week 24 (erythema, 36.7% vs 22.6%; pustules, 63.3% vs 45.2%; scaling/crusting, 36.7% vs 19.4%; total score, 33.3% vs 19.4%) and Week 48 (erythema, 36.7% vs 22.6%; pustules, 66.7% vs 45.2%; scaling/crusting, 43.3% vs 25.8%; total score, 36.7% vs 22.6%). There were no new flares after Week 4 in high-dose spesolimab group; however, flares increased with placebo (45.2% at Week 24; 51.6% at Week 48).&#x0D; Conclusion: Versus placebo, high-dose subcutaneous spesolimab resulted in a greater proportion of patients maintaining GPPGA scores of 0, a lower proportion having flares at Week 4, and no new flares after Week 4. This was sustained at Weeks 24 and 48.

Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial

IntroductionExtensive-stage SCLC (ES-SCLC) prognosis remains poor. The phase 3 RATIONALE-312 study aimed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment for ES-SCLC. MethodsRATIONALE-312 is a randomized, double-blind, placebo-controlled trial, conducted in the People's Republic of China. Eligible patients with previously untreated ES-SCLC were randomized 1:1 to receive four cycles of tislelizumab 200 mg or placebo, with etoposide plus carboplatin or cisplatin intravenously every 3 weeks, followed by tislelizumab 200 mg or placebo as maintenance. The primary end point was overall survival (OS). Secondary end points included progression-free survival and safety. ResultsBetween July 22, 2019 and April 21, 2021, 457 patients were randomized to tislelizumab (n = 227) or placebo (n = 230), plus chemotherapy. Baseline demographics were generally balanced between arms. At the data cutoff (April 19, 2023), the median study follow-up was 14.2 months (interquartile range: 8.6–25.3). Tislelizumab plus chemotherapy exhibited a statistically significant OS benefit versus placebo plus chemotherapy (stratified hazard ratio = 0.75 [95% confidence interval (CI): 0.61–0.93]; one-sided p = 0.0040; median: 15.5 [95% CI: 13.5–17.1] versus 13.5 mo [95% CI: 12.1–14.9], respectively). Progression-free survival was significantly improved in the tislelizumab versus placebo arm (stratified hazard ratio = 0.64 [95% CI: 0.52–0.78]; p < 0.0001; median: 4.7 [95% CI: 4.3–5.5] versus 4.3 mo [95% CI: 4.2–4.4], respectively). Grade greater than or equal to 3 treatment-related adverse events were reported in 86% of patients in each treatment arm and were mostly hematologic. ConclusionsTislelizumab plus chemotherapy exhibited statistically significant clinical benefit and manageable safety compared with placebo plus chemotherapy as first-line treatment in patients with advanced ES-SCLC.

Cannabidiol for Postoperative Pain Control After Arthroscopic Rotator Cuff Repair Demonstrates No Deficits in Patient-Reported Outcomes Versus Placebo: 1-Year Follow-up of a Randomized Controlled Trial.

Cannabidiol (CBD) has been shown recently to positively affect patient pain and satisfaction immediately after arthroscopic rotator cuff repair (ARCR). However, it is unclear whether the addition of CBD to a perioperative regimen could affect postoperative outcomes. To evaluate patient-reported outcomes among patients who underwent ARCR and received buccally absorbed CBD or an identical placebo for early postoperative pain management at 1-year follow-up. Randomized controlled trial; Level of evidence, 2. Eligible patients had previously participated in a multicenter, placebo-controlled, randomized, double-blinded trial that evaluated the analgesic effects of CBD in the immediate postoperative period after ARCR. The experimental group received 25 mg of CBD 3 times/day if <80 kg and 50 mg of CBD 3 times/day if >80 kg for 14 days, with the control group receiving an identical placebo. The following outcomes were assessed at minimum 1-year follow-up: visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE), and patient satisfaction. The rates of achievement of the Patient Acceptable Symptom State (PASS) were compared based on ASES at latest follow-up. Continuous and categorical variables were compared with the Mann-Whitney U test and Fisher exact test, respectively. Follow-up was obtained from 83 of 99 patients (83.8%) who completed the original trial. There were no significant differences between the CBD and control groups with respect to age, sex, body mass index, rate of concomitant procedures, or number of anchors used intraoperatively. At 1-year follow-up, there were no significant differences between the CBD and control groups in VAS pain (0.8 vs 1.2, P = .38), ASES (93.0 vs 91.1, P = .71), SANE (87.6 vs 90.1, P = .24), or satisfaction (97.4 vs 95.4, P = .41). A majority of patients achieved the PASS (81.0% [CBD] vs 77.5% [control]; P = .79). Perioperative use of CBD for pain control among patients undergoing ARCR did not result in any significant deficits in pain, satisfaction, or patient-reported outcomes at 1-year postoperatively compared with a placebo control group. These findings suggest that CBD can be considered in a postoperative multimodal pain management regimen without detrimental effects on outcome. NCT04672252 (ClinicalTrials.gov identifier).

Health-Related Quality of Life with Gilteritinib Versus Placebo Post-Transplant Maintenance for FLT3-ITD+ Acute Myeloid Leukemia (AML): A Quality of Life Analysis from BMT CTN 1506

Health-Related Quality of Life with Gilteritinib Versus Placebo Post-Transplant Maintenance for FLT3-ITD+ Acute Myeloid Leukemia (AML): A Quality of Life Analysis from BMT CTN 1506