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This multicenter, randomized trial showed significant benefit of propranolol for the treatment of infantile hemangiomas. Infantile hemangiomas are the most common soft-tissue tumors of childhood, occurring in 3 to 10% of infants. 1 – 4 Lesions are usually not developed at birth and are generally diagnosed during the first 4 to 6 weeks of life, with most growth during the first 5 months. 5 The characteristic evolution of nearly all infantile hemangiomas is proliferation, stabilization, and slow, spontaneous involution. Although most lesions follow an uncomplicated clinical course, approximately 12% result in complications requiring referral to a specialist. 6 , 7 Many infantile hemangiomas leave permanent sequelae, with potential psychological effects in the children and their parents. 8 , 9 Historically, systemic glucocorticoids . . .

Clinical decompensation of cirrhosis is associated with poor prognosis. Clinically significant portal hypertension (CSPH), defined by a hepatic venous pressure gradient (HVPG) ≥10 mm Hg, is the strongest predictor of decompensation. This study aimed at assessing whether lowering HVPG with β blockers could decrease the risk of decompensation or death in compensated cirrhosis with CSPH. This study on β blockers to prevent decompensation of cirrhosis with portal hypertension (PREDESCI) was an investigator-initiated, double-blind, randomised controlled trial done in eight hospitals in Spain. We enrolled patients with compensated cirrhosis and CSPH without high-risk varices. All participants had HVPG measurements with assessment of acute HVPG-response to intravenous propranolol. Responders (HVPG-decrease ≥10%) were randomly assigned to propranolol (up to 160 mg twice a day) versus placebo and non-responders to carvedilol (≤25 mg/day) versus placebo. Doses were individually determined during an open-label titration period after which randomisation was done with 1:1 allocation by a centralised web-based system. The primary endpoint was incidence of cirrhosis decompensation (defined as development of ascites, bleeding, or overt encephalopathy) or death. Since death in compensated cirrhosis is usually unrelated to the liver, an intention-to-treat analysis considering deaths unrelated to the liver as competing events was done. This study is registered with ClinicalTrials.gov, number NCT01059396. The trial is now completed. Between Jan 18, 2010, and July 31, 2013, 631 patients were evaluated and 201 were randomly assigned. 101 patients received placebo and 100 received active treatment (67 propranolol and 33 carvedilol). The primary endpoint occurred in 16 (16%) of 100 patients in the β blockers group versus 27 (27%) of 101 in the placebo group (hazard ratio [HR] 0·51, 95% CI 0·26–0·97, p=0·041). The difference was due to a reduced incidence of ascites (HR 0·42, 95% CI 0·19–0·92, p=0·03). The overall incidence of adverse events was similar in both groups. Six patients (four in the β blockers group) had severe adverse events. Long-term treatment with β blockers could increase decompensation-free survival in patients with compensated cirrhosis and CSPH, mainly by reducing the incidence of ascites. Spanish Ministries of Health and Economy.

Background Alcohol craving and relapse occur after the reactivation of alcohol reward memory. Previous studies suggest that drug-associated memory undergoes reconsolidation once retrieved by drug-associated stimuli. This study hypothesized that propranolol administration during memory reconsolidation induced by conditioned stimulus (CS) would significantly attenuate alcohol craving. Methods A total of 40 patients with alcohol dependence who met the diagnostic criteria for alcohol dependence in DSMV were enrolled. The patients were randomized located into the memory retrievalpropranolol group ( n  = 20) and the memory retrievalplacebo group ( n  = 20) using the random number table. The memory retrievalpropranolol group used propranolol combined with a memory retrieval reconsolidation procedure, while the memory retrievalplacebo group used a placebo combined with a memory retrieval reconsolidation procedure. The Visual Analog Scale (VAS) was used to evaluate the degree of alcohol craving induced by images at stages of baseline measures, relevance learning, and memory test. The systolic blood pressure, diastolic blood pressure, and heartrate were applied to evaluate cue responsiveness. Repeated measures analysis of variance was used to compare the craving degree and independent samples t-tests were used for comparing demographic characteristics, scale scores between alcohol-dependent patient groups, and pre-post differences in heart rate, systolic blood pressure, and diastolic blood pressure at each experimental phase. Results Relevance learning stage: Compared with before learning, the levels of systolic blood pressure, diastolic blood pressure, and heart rate of the two groups increased in varying degrees after learning conditional stimulationrelevance learning CS+(all P  < 0.05). Compared with pre-learning, both groups showed increased VAS scores during the Retrieval phase with statistically significant differences ( F  = 47.294、25.015, all P  < 0.001). The memory test stage, after re-exposure to learned CS+, both groups showed varying degrees of increase in heart rate, systolic blood pressure, and diastolic blood pressure, with all differences reaching statistical significance (all P  < 0.05). During the test phase, statistically significant between-group differences were found in heart rate difference, systolic blood pressure difference and diastolic blood pressure difference between the two groups (all P  < 0.05). the retrieval-propranolol group demonstrated decreased VAS scores with statistical significance ( F  = 56.017, P  < 0.001), while the retrieval-placebo group showed no statistically significant alterations in VAS scores ( F  = 0.183, P  > 0.05). Conclusions Our study demonstrated that propranolol administration after CS-induced retrieval could disrupt alcohol-associated memory reconsolidation and reduce alcohol craving. The finding provided a potential translational method to treat alcohol use disorder. Trial registration The protocol was registered at www.chictr.org.cn on October 13, 2023 (Chinese Clinical Trial Registry, identification number ChiCTR2300076633, Retrospectively registered).

Background Cerebral cavernous malformations (CCMs) are vascular malformations characterized by clusters of enlarged leaky capillaries in the central nervous system. They may result in intracranial haemorrhage, epileptic seizure(s), or focal neurological deficits, and potentially lead to severe disability. Globally, CCMs represent the second most common intracranial vascular malformation in humans, and their familial form (FCCMs) accounts for one-fifth of cases. Neurosurgical excision, and perhaps stereotactic radiosurgery, is the only available therapeutic option. Case reports suggest that propranolol might modify disease progression. Methods Treat_CCM is a prospective, randomized, open-label, blinded endpoint (PROBE), parallel-group trial involving six Italian clinical centres with central reading of brain magnetic resonance imaging (MRI) and adverse events. Patients with symptomatic FCCMs are randomized (2:1 ratio) either to propranolol (40–80 mg twice daily) in addition to standard care or to standard care alone (i.e. anti-epileptic drugs or headache treatments). The primary outcome is intracranial haemorrhage or focal neurological deficit attributable to CCMs. The secondary outcomes are MRI changes over time (i.e. de novo CCM lesions, CCM size and signal characteristics, iron deposition, and vascular leakage as assessed by quantitative susceptibility mapping and dynamic contrast enhanced permeability), disability, health-related quality of life, depression severity, and anxiety (SF-36, BDI-II, State-Trait Anxiety Inventory). Discussion Treat_CCM will evaluate the safety and efficacy of propranolol for CCMs following promising case reports in a randomized controlled trial. The direction of effect on the primary outcome and the consistency of effects on the secondary outcomes (even if none of them yield statistically significant differences) of this external pilot study may lead to a larger sample size in a definitive phase 2 trial. Trial registration ClinicalTrails.gov, NCT03589014 . Retrospectively registered on 17 July 2018.

The objective of this phase 1 study was to evaluate the pharmacokinetics (PK), pharmacodynamics, and cardiac effect following administration of ponesimod (a selective sphingosine‐1‐phosphate receptor modulator) and propranolol in healthy adults. In treatment period (TP) 1, participants received ponesimod (2 mg). In TP2, if resting heart rate (HR) was ≥ 55 bpm, the ponesimod up‐titration regimen was initiated. Participants were randomized to TP2A (placebo plus ponesimod up‐titration) or TP2B (80 mg propranolol plus ponesimod up‐titration). Concomitant administration resulted in an increased bradyarrhythmic effect on HR versus ponesimod alone. The mean maximum difference in mean hourly HR from time‐matched baseline for TP2B compared with TP2A during the first 12 h post‐dose was −12.4 bpm. This was observed after the first dose of ponesimod, persisted for the first 4 doses, then decreased to −7.4 bpm post‐up‐titration. The lowest mean of the HRnadir in TP2B was 48.9 bpm (95% CI: 46.4–51.3). There was no significant difference in the occurrence of 1st degree AV block between groups and no occurrences of 2nd or higher degree AV block. No clinically relevant changes were observed in the PK of ponesimod or propranolol. Overall, 88.5% of participants experienced ≥ 1 AE during the study. In TP2, the most reported TEAEs (≥ 5%) considered related to ponesimod were fatigue (12 [25.5%]) and dizziness (10 [21.3%]). No deaths were reported. Co‐administration of ponesimod with propranolol resulted in a greater HR‐lowering effect compared to ponesimod alone, without significant changes in PK parameters or serious cardiac adverse events in healthy adults.

This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups ( p  = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury ( p  = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI ( p  = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p  = 0.001), GCS (r = − 0.125, p  = 0.02), and serum S100B (r = 0.205, p  = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI. Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28–30, 2024, in Estoril, Lisbon, Portugal.

Background Propranolol, a non-selective beta-blocker, commonly used to prevent variceal bleed, but might precipitate circulatory dysfunction in severe ascites. Midodrine, an alpha-1 adrenergic agonist improves renal perfusion and systemic hemodynamics. Addition of midodrine might facilitate higher maximum tolerated dose (MTD) of propranolol, thereby less risk of variceal bleed in cirrhosis patients with severe ascites. Methods 140 patients with cirrhosis and severe/refractory ascites were randomized- propranolol and midodrine (Gr.A, n  = 70) or propranolol alone (Gr.B, n  = 70). Primary outcome was incidence of bleed at 1 year. Secondary outcomes included ascites control, achievement of target heart rate (THR), HVPG response and adverse effects. Results Baseline characteristics were comparable between two groups. Cumulative incidence of bleed at 1 year was lower in Gr.A than B (8.5%vs.27.1%, p -0.043). The MTD of propranolol was higher in Gr.A (96.67 ± 36.6 mg vs. 76.52 ± 24.4 mg; p -0.01) and more patients achieved THR (84.2%vs.55.7%, p -0.034). Significantly higher proportion of patients in Gr.A had complete resolution of ascites [17.1%vs.11.4%, p -0.014), diuretic tolerance (80%vs.60%, p -0.047) at higher doses( p -0.02) and lesser need for paracentesis. Patients in Gr.A also had greater reduction in variceal grade (75.7%vs.55.7%; p -0.01), plasma renin activity (54.4% from baseline) ( p  = 0.02). Mean HVPG reduction was greater in Gr.A than B [4.38 ± 2.81 mmHg(23.5%) vs. 2.61 ± 2.87 mmHg(14.5%), p -0.045]. Complications like post-paracentesis circulatory dysfunction and spontaneous bacterial peritonitis on follow-up were higher in Gr.B than A (22.8%vs.51.4%, p  = 0.013 and 10%vs.15.7%, p  = 0.03, respectively). Conclusion Addition of midodrine facilitates effective use of propranolol in higher doses and greater HVPG reduction, thereby preventing first variceal bleed, reduced paracentesis requirements with fewer ascites- related complications in patients with cirrhosis with severe/refractory ascites.

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. This study evaluated safety and efficacy of propranolol eye micro-drops in preterm newborns with ROP. Methods: A multicenter open-label trial, planned according to the Simon optimal two-stage design, was performed to analyze safety and efficacy of propranolol micro-drops in newborns with stage 2 ROP. To this end, hemodynamic and respiratory parameters were monitored, and blood samples were collected weekly, for 3 wk. Propranolol plasma levels were also monitored. The progression of the disease was evaluated with serial ophthalmologic examinations. Results: Twenty-three newborns were enrolled. Since the fourth of the first 19 newborns enrolled in the first stage of the study showed a progression to stage 2 or 3 with plus, the second stage was prematurely discontinued. Even though the objective to complete the second stage was not achieved, the percentage of ROP progression (26%) was similar to that obtained previously with oral propranolol administration. However, no adverse effects were observed and propranolol plasma levels were significantly lower than those measured after oral administration. Conclusion: Propranolol 0.1% eye micro-drops are well tolerated, but not sufficiently effective. Further studies are required to identify the optimal dose and administration schedule.

Background The Induction of labor is the most common obstetric procedure in daily practice. Introducing propranolol as a new drug to augment the action of prostaglandins will help in the induction process and decrease CS rates. Several researchers have used propranolol in the augmentation of labor. Aim This pilot study compares propranolol and misoprostol versus misoprostol alone for labor induction in primigravids. Methods This is a Randomized clinical trial, single-blinded, placebo-controlled trial at Ain Shams University Maternity hospital. This study included 128 pregnant full-term primigravid women candidates for labor induction, randomized into two groups. All candidates underwent labor induction with 25 µg of vaginal misoprostol. Group I received 20 mg of oral propranolol tablets, while group II received sugary pills as a placebo. Candidates who responded successfully to induction were assessed for possible augmentation of labor by amniotomy or oxytocin infusion. The Primary outcome was induction to delivery interval, while the secondary outcomes were the duration of the latent phase, mode of delivery, and APGAR score of the neonate. Results The induction-delivery time was (11.8 ± 8.1 h. vs. 12.6 ± 8.9 h., P value = 0.027) and the duration of the latent phase of labor (7.9 ± 5.6 h. vs. 9.2 ± 6.03 h., P value = 0.017) were significantly shorter in the group of misoprostol and propranolol compared to the group of misoprostol and placebo. There was no statistically significant difference between both groups’ mode of delivery, indications for cesarean section, misoprostol, and oxytocin doses, or neonatal outcome. (P value > 0.05). Conclusion Propranolol, when used with misoprostol for induction of labor, results in augmentation of action of misoprostol and a significantly shorter induction-delivery interval. Trial registration We retrospectively registered this trial in clinicaltrial.gov on 01/09/2020 (NCT04533841). https://clinicaltrials.gov/ct2/show/NCT04533841

BackgroundStroke-induced transient immune suppression is believed to contribute to post-stroke infections. The β-adrenergic receptor antagonist, propranolol, has been shown to prevent stroke-associated pneumonia (SAP) via reversing post-stroke immunosuppression in preclinical studies and in retrospective analysis in stroke patients. However, whether propranolol can reduce the risk of SAP has not been tested in prospective, randomised controlled trials.AimTo describe the rationale and design of a multicentre, prospective, open-label, endpoint-blinded, randomised controlled study to evaluate the safety and efficacy of propranolol hydrochloride injection for the prevention of SAP in patients with intracerebral haemorrhage (ICH) (PROCHASE).DesignIn this investigator-initiated trial, we compare the safety of the standard medical treatment to standard medical treatment plus intravenous propranolol hydrochloride administration (5 mg daily on days 1–7) in patients with ICH and the efficacy of this intervention to reduce the occurrence of SAP. All patients will be followed up for 90±7 days.Study outcomesThe primary efficacy outcome is SAP within 7±1 days diagnosed by the defined algorithm based on a diagnosis of SAP recommendations from the pneumonia in stroke consensus group. The primary safety outcome is defined as severe or moderate bradycardia within 7±1 days. The secondary outcome is a modified Rankin score of 0–3 at 90±7 days after randomisation.DiscussionThe PROCHASE trial aims to generate clinical evidence regarding the safety and efficacy of propranolol in preventing SAP in patients with ICH.