Effect of Cotherapy Reduction on Tolerability of Epilepsy Add-On Therapy: A Randomized Controlled Trial

2005 ◽  
Vol 39 (3) ◽  
pp. 418-423 ◽  
Author(s):  
Dean K Naritoku ◽  
Joseph F Hulihan ◽  
Lesley Kraut Schwarzman ◽  
Marc Kamin ◽  
William H Olson
Keyword(s):  
Adverse Events ◽  
Dose Group ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Primary Study ◽  
Open Label ◽  
Open Label Study ◽  
Effective Doses ◽  
Receive Treatment ◽  
To Receive

BACKGROUND: Adverse effects are the most common cause for failure of an antiepileptic drug (AED), especially when an AED is added to existing therapy. With the increased drug load, it may not be possible to titrate the newly added AED to effective doses. Reducing the dosage of AED cotherapy as the new drug is introduced may improve tolerability. OBJECTIVE: To evaluate reduction of AED cotherapy as a strategy to improve tolerability and patient retention when a new AED is added to existing therapy. METHODS: In a 20-week, randomized, open-label study, topiramate was initiated as add-on therapy in adults and adolescents (⩾12 y of age) with inadequately controlled partial-onset seizures. Patients were randomized to receive treatment in which adverse events could be managed by adjustments in AED cotherapy (flex-dose group) or treatment in which AED cotherapy dosages remained fixed (fixed-dose group). Topiramate could be adjusted as needed in both groups. In the flex-dose group, patients exited randomized treatment when topiramate was discontinued. In the fixed-dose group, patients exited when AED cotherapy was reduced due to adverse events or when topiramate was discontinued. The primary study outcome was the percentage of patients exiting randomized treatment due to adverse events. RESULTS: The flex-dose group comprised 297 patients; 302 patients were in the fixed-dose group. Significantly fewer patients in the flex-dose group exited the study due to adverse events (16% vs 23% in the fixed-dose group; p = 0.02). In the flex-dose group, 10% (17 of 168) of patients discontinued topiramate due to adverse events after AED cotherapy was reduced versus 22% (29 of 129) when AED cotherapy was not reduced. CONCLUSIONS: Reduction of AED cotherapy is a useful strategy to improve tolerability and retention when topiramate is initiated as adjunctive therapy.

scholarly journals Pegloticase in combination with methotrexate in patients with uncontrolled gout: A multicenter, open-label study (MIRROR)

2020 ◽  
pp. jrheum.200460 ◽  
Author(s):  
John K. Botson ◽  
John R.P. Tesser ◽  
Ralph Bennett ◽  
Howard M. Kenney ◽  
Paul M. Peloso ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Randomized Study ◽  
Primary Study ◽  
Efficacy And Safety ◽  
Open Label ◽  
Safety Study ◽  
Open Label Study ◽  
Randomized Controlled ◽  
Intent To Treat ◽  
Treat Population

Objective To examine the efficacy and safety of pegloticase in combination with methotrexate in patients with uncontrolled gout in an exploratory, open-label clinical trial (NCT03635957) prior to a randomized, controlled trial. Methods A multicenter, open-label, efficacy and safety study of pegloticase with methotrexate cotreatment was conducted in patients with uncontrolled gout. Patients were administered oral methotrexate (15 mg/week) and folic acid (1 mg/day) 4 weeks prior to and throughout pegloticase treatment. The primary study outcome was the proportion of responders, defined as sUA <6 mg/dL for ≥80% of the time during month 6 (weeks 20, 22, and 24). All analyses were performed on a modified intent-to-treat population, defined as patients who received ≥1 pegloticase infusion. Results Seventeen patients were screened and 14 patients (all men, average age: 49.3 ± 8.7 years) were enrolled. On Day 1, mean sUA was 9.2 ± 2.5 mg/dL and 12 of the 14 patients had visible tophi. At the 6 month timepoint, 11/14 (78.6%, 95%CI 49.2-95.3%) met the responder definition, with 3 patients discontinuing after meeting protocol-defined treatment discontinuation rules (pre-infusion sUA values greater than 6 mg/dL at 2 consecutive scheduled visits). All patients tolerated methotrexate. No new safety concerns were identified. Conclusion In this study, an increased proportion of patients maintained therapeutic response at 6 months when treated concomitantly with methotrexate and pegloticase when compared to the previously reported 42% using pegloticase alone. These results support the need for a randomized study of methotrexate or placebo with pegloticase to validate these open label findings.

Impact of Temperature on Injection-Related Pain Caused by Subcutaneous Administration of Ustekinumab: A Three-arm Crossover Open-label Randomized Controlled Trial

2017 ◽  
Vol 1 (3) ◽  
pp. 117-127
Author(s):  
Yasaman Mansouri ◽  
Yasmin Amir ◽  
Michelle Min ◽  
Raveena Khanna ◽  
Ruiqi Huang ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Subcutaneous Administration ◽  
Open Label ◽  
Post Dose ◽  
Subcutaneous Injections ◽  
Pain Scores ◽  
Observational Cohort ◽  
Vas Scores ◽  
Pre Treatment ◽  
To Receive

Background: Adherence to subcutaneous biologic agents for the treatment of psoriasis can be negatively influenced by injection pain.Objective: To explore the differences in injection site pain when patients are pre-treated with heat or cold, versus no pre-treatment prior to administration of a subcutaneous biologic agent.Methods: In an observational cohort study, patients receiving subcutaneous injections of ustekinumab were randomly assigned to receive pretreatment with ice, heat, or no intervention over three visits. Post-dose, patients rated pain on a 100 mm visual analogue scale (VAS).Results: There was an increase in the VAS score for both heat (2.51, P=0.30) and ice (3.33, P=0.16), compared to no intervention. No differences were found between the two intervention groups (-0.83, P=0.73). On average, females had the same VAS scores with ice compared to that of no intervention (-0.12, P=0.97) and a non–significant decrease of 3.29 points (P=0.38) with heat. Males had increased pain scores by 5.65 points (P=0.07) with ice and by 6.39 points (P=0.04) with heat.Limitations: Pain is a subjective measurement and objective quantification is difficult.Conclusions: On average, neither heat nor cold application reliably reduced pain. Our results do not support the application of heat or cold prior to ustekinumab injection.

Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial

2020 ◽  
pp. 27-37
Author(s):  
Suresh Durgam ◽  
Willie Earley ◽  
Rui Li ◽  
Dayong Li ◽  
Kaifeng Lu ◽  
...  
Keyword(s):  
Safety Profile ◽  
Relapse Prevention ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Controlled ◽  
Time To Relapse

Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97 weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3—9 mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9 mg/d) or placebo for double-blind treatment (up to 72 weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n = 99) or cariprazine (n = 101). Time to relapse was significantly longer in cariprazine — versus placebo-treated patients (P = .0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥ 10% of patients during open-label treatment; there were no cariprazine adverse events ≥ 10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060. Key words: schizophrenia; cariprazine; long-term treatment; relapse prevention; randomized controlled trial; oral antipsychotics

scholarly journals Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study

2020 ◽  
Vol 8 (1) ◽  
pp. e000773
Author(s):  
Carol H Wysham ◽  
Julio Rosenstock ◽  
Marion L Vetter ◽  
Hui Wang ◽  
Elise Hardy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Study ◽  
Registration Number ◽  
Efficacy Measures ◽  
Design And Methods ◽  
To Receive

IntroductionInvestigate the effects of switching from two times per day exenatide to once-weekly exenatide administered by autoinjector (exenatide once-weekly suspension by autoinjector (QWS-AI)) or treatment with exenatide QWS-AI for 1 year.Research design and methodsIn this phase III open-label study, adults with type 2 diabetes were randomized to receive exenatide QWS-AI (2 mg) or exenatide two times per day (5 mcg for 4 weeks, followed by 10 mcg) for 28 weeks. During a subsequent non-randomized 24-week extension, patients who received exenatide two times per day were switched to exenatide QWS-AI and those randomized to exenatide QWS-AI continued this treatment. Efficacy measures included changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), and body weight.ResultsIn total, 315 patients (mean baseline A1C of 8.5%) completed the initial 28 weeks of randomized treatment with exenatide QWS-AI (n=197) or exenatide two times per day (n=118) and were included in the 24-week extension (mean A1C of 7.0% and 7.3%, respectively, at week 28). From weeks 28–52, patients who switched from exenatide two times per day to exenatide QWS-AI had additional A1C reductions of approximately 0.5% (mean A1C change from baseline of –1.4% at week 52) and further reductions from baseline in FPG. Patients who continued exenatide QWS-AI treatment for 52 weeks showed clinically relevant A1C reductions (mean A1C change from baseline of –1.3% at week 52). Body-weight reductions achieved through week 28 were sustained at week 52 in both groups. There were no unexpected safety concerns or changes in the safety profile among patients who switched from exenatide two times per day to exenatide QWS-AI or those who continued exenatide QWS-AI treatment for 52 weeks.ConclusionsSwitching from exenatide two times per day to exenatide QWS-AI resulted in further A1C reductions and maintenance of earlier decreases in body weight, while continued therapy with exenatide QWS-AI for 52 weeks maintained A1C and body-weight reductions, without additional safety or tolerability concerns.Trial registration numberNCT01652716.

scholarly journals The effects of a limited infusion rate of fluid in the early resuscitation of sepsis on glycocalyx shedding measured by plasma syndecan-1: a randomized controlled trial

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jutamas Saoraya ◽  
Lipda Wongsamita ◽  
Nattachai Srisawat ◽  
Khrongwong Musikatavorn
Keyword(s):  
Adverse Events ◽  
Organ Failure ◽  
Fluid Resuscitation ◽  
Infusion Rate ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Endothelial Glycocalyx ◽  
Open Label ◽  
Randomized Controlled ◽  
Standard Rate

Abstract Background Aggressive fluid administration is recommended in the resuscitation of septic patients. However, the delivery of a rapid fluid bolus might cause harm by inducing degradation of the endothelial glycocalyx. This research aimed to examine the effects of the limited infusion rate of fluid on glycocalyx shedding as measured by syndecan-1 in patients with sepsis-induced hypoperfusion. Methods A prospective, randomized, controlled, open-label trial was conducted between November 2018 and February 2020 in an urban academic emergency department. Patients with sepsis-induced hypoperfusion, defined as hypotension or hyperlactatemia, were randomized to receive either the standard rate (30 ml/kg/h) or limited rate (10 ml/kg/h) of fluid for the first 30 ml/kg fluid resuscitation. Subsequently, the fluid rate was adjusted according to the physician’s discretion but not more than that of the designated fluid rate for the total of 6 h. The primary outcome was differences in change of syndecan-1 levels at 6 h compared to baseline between standard and limited rate groups. Secondary outcomes included adverse events, organ failure, and 90-day mortality. Results We included 96 patients in the intention-to-treat analysis, with 48 assigned to the standard-rate strategy and 48 to the limited-rate strategy. The median fluid volume in 6 h in the limited-rate group was 39 ml/kg (interquartile range [IQR] 35–52 ml/kg) vs. 53 ml/kg (IQR 46–64 ml/kg) in the standard-rate group (p < 0.001). Patients in the limited-rate group were less likely to received vasopressors (17% vs 42%; p = 0.007) and mechanical ventilation (20% vs 41%; p = 0.049) during the first 6 h. There were no significantly different changes in syndecan-1 levels at 6 h between the two groups (geometric mean ratio [GMR] in the limited-rate group, 0.82; 95% confidence interval [CI], 0.66–1.02; p = 0.07). There were no significant differences in adverse events, organ failure outcomes, or mortality between the two groups. Conclusions In sepsis resuscitation, the limited rate of fluid resuscitation compared to the standard rate did not significantly reduce changes in syndecan-1 at 6 h. Trial registration Thai Clinical Trials Registry number: TCTR20181010001. Registered 8 October 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=4064

scholarly journals Comparison of Safety and Tolerability of Deutetrabenazine During Titration and Maintenance in Patients with Tardive Dyskinesia

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 164-180
Author(s):  
Amanda Wilhelm ◽  
Karen E. Anderson ◽  
Hubert H. Fernandez ◽  
Hadas Barkay ◽  
Nayla Chaijale ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Adverse Events ◽  
Tardive Dyskinesia ◽  
Dry Mouth ◽  
Fixed Dose ◽  
Open Label ◽  
Serious Adverse Events ◽  
Open Label Extension ◽  
Pharmaceutical Industries ◽  
Flexible Dose

AbstractBackgroundDeutetrabenazine is approved to treat tardive dyskinesia (TD) in adults and is titrated weekly by 6 mg/day, from 12 to 48 mg/day, based on dyskinesia control and tolerability. This analysis compared the safety of deutetrabenazine during titration versus maintenance.MethodsSafety was assessed during titration versus maintenance using integrated data from two 12-week placebo-controlled studies (ARM-TD and AIM-TD) and the open-label extension study. Rates were compared for overall and serious adverse events (AEs), AEs leading to discontinuation, treatment-related AEs, common AEs (≥4%), and specific AEs (parkinsonism, suicidal ideation, akathisia, restlessness).ResultsIn titration versus maintenance, AE rates with placebo (n=130) were: overall, 43.1% vs 25.4%; serious, 4.6% vs 2.3%; leading to discontinuation, 3.1% vs 0; treatment-related, 26.9% vs 10.0%. For placebo, common AEs during titration were somnolence, headache, nausea, fatigue, and dry mouth; none occurred during maintenance. In titration versus maintenance, AE rates in fixed-dose deutetrabenazine 12–36 mg (n=216) were: overall, 33.3–38.9% vs 22.2–29.2%; serious, 2.8–6.9% vs 0–1.4%; leading to discontinuation, 2.8–5.6% vs 0; treatment-related, 8.3–16.7% vs 8.3–13.9%. For fixed-dose deutetrabenazine, common AEs during titration were headache, diarrhea, nasopharyngitis, depression, hypertension, and dry mouth; headache was the only common AE during maintenance. In titration versus maintenance, AE rates with flexible-dose deutetrabenazine (n=168) were: overall, 49.4% vs 32.7%; serious, 3.6% vs 2.4%; leading to discontinuation, 2.4% vs 0.6%. For flexible-dose deutetrabenazine, the only common AE during titration was somnolence; none occurred during maintenance. Rates of parkinsonism, suicidal ideation, akathisia, and restlessness were low and comparable in titration and maintenance.ConclusionsDeutetrabenazine was well-tolerated, with AE rates similar to placebo during both phases; AE rates were higher during titration and decreased during maintenance.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

scholarly journals Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kensuke Nakamura ◽  
◽  
Aiki Marushima ◽  
Yuji Takahashi ◽  
Akio Kimura ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Adverse Events ◽  
Controlled Trial ◽  
Insurance Coverage ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Consciousness Disturbance ◽  
Multicenter Randomized Controlled Trial ◽  
Severe Adverse Events

Abstract Background Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is important. Phenytoin and fosphenytoin, the prodrug of phenytoin with less severe adverse effects, have been recommended as second-line treatments. However, fosphenytoin causes severe adverse events, such as hypotension and arrhythmia. Levetiracetam reportedly has similar efficacy and higher safety for SE; however, evidence to support its use for adult SE is lacking. In the present study, a non-inferiority designed multicenter randomized controlled trial (RCT) is being conducted to compare levetiracetam with fosphenytoin after diazepam as a second-line treatment for SE. Methods This multicenter, prospective, and open-label RCT is conducted in emergency departments. Between December 23, 2019, and March 31, 2023, 176 patients with convulsive SE transported to an emergency room will be randomized into a fosphenytoin group and levetiracetam group at a ratio of 1:1. The definition of SE is “continuous seizures longer than 5 min or discrete seizures longer than 2 min with intervening consciousness disturbance.” In both groups, diazepam is initially administered at 1–20 mg, followed by intravenous fosphenytoin at 22.5 mg/kg or intravenous levetiracetam at 1000–3000 mg. The primary outcome is the seizure cessation rate within 30 min. Seizure recurrence within 24 h, severe adverse events, and intubation rate within 24 h are secondary outcomes. Discussion The present study was approved and conducted as an initiative study of the Japanese Association for Acute Medicine. If non-inferiority is identified, the society will pursue an application for the national health insurance coverage of levetiracetam for SE via a public knowledge-based application. Trial registration Japan Registry of Clinical Trials jRCTs031190160. Registered on December 13, 2019

scholarly journals Effectiveness of Measures to Eradicate Staphylococcus aureus Carriage in Patients with Community-Associated Skin and Soft-Tissue Infections: A Randomized Trial

2011 ◽  
Vol 32 (9) ◽  
pp. 872-880 ◽  
Author(s):  
Stephanie A. Fritz ◽  
Bernard C. Camins ◽  
Kimberly A. Eisenstein ◽  
Joseph M. Fritz ◽  
Emma K. Epplin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Soft Tissue ◽  
Controlled Trial ◽  
Control Group ◽  
Open Label ◽  
Intention To Treat ◽  
Intranasal Mupirocin ◽  
Mupirocin Ointment ◽  
Hygiene Education ◽  
To Receive

Background.Despite a paucity of evidence, decolonization measures are prescribed for outpatients with recurrent Staphylococcus aureus skin and soft-tissue infection (SSTI).Objective.Compare the effectiveness of 4 regimens for eradicating S. aureus carriage.Design.Open-label, randomized controlled trial. Colonization status and recurrent SSTI were ascertained at 1 and 4 months.Setting.Barnes-Jewish and St. Louis Children's Hospitals, St. Louis, Missouri, 2007–2009.Participants.Three hundred patients with community-onset SSTI and S. aureus colonization in the nares, axilla, or inguinal folds.Interventions.Participants were randomized to receive no therapeutic intervention (control subjects) or one of three 5-day regimens: 2% mupirocin ointment applied to the nares twice daily, intranasal mupirocin plus daily 4% chlorhexidine body washes, or intranasal mupirocin plus daily dilute bleach water baths.Results.Among 244 participants with 1-month colonization data, modified intention-to-treat analysis revealed S. aureus eradication in 38% of participants in the education only (control) group, 56% of those in the mupirocin group (P = .03 vs controls), 55% of those in the mupirocin and chlorhexidine group (P = .05), and 63% off those in the mupirocin and bleach group (P = .006). Of 229 participants with 4-month colonization data, eradication rates were 48% in the control group, 56% in the mupirocin only group (P = .40 vs controls), 54% in the mupirocin and chlorhexidine group (P = .51), and 71% in the mupirocin and bleach group (P = .02). At 1 and 4 months, recurrent SSTIs were reported by 20% and 36% of participants, respectively.Conclusions.An inexpensive regimen of dilute bleach baths, intranasal mupirocin, and hygiene education effectively eradicated S. aureus over a 4-month period. High rates of recurrent SSTI suggest that factors other than endogenous colonization are important determinants of infection.Trial Registration.ClinicalTrials.gov identifier: NCT00513799.

Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study

2017 ◽  
Vol 76 (12) ◽  
pp. 2065-2070 ◽  
Author(s):  
Lisa K Stamp ◽  
Peter T Chapman ◽  
Murray Barclay ◽  
Anne Horne ◽  
Christopher Frampton ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Escalation ◽  
Controlled Trial ◽  
Serum Urate ◽  
Extension Study ◽  
Open Label ◽  
Serious Adverse Events ◽  
Open Label Extension ◽  
Randomised Controlled ◽  
Kidney Impairment

ObjectivesTo determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout.MethodsPeople, including those with chronic kidney disease, who completed the first 12 months of a randomised controlled trial continued into a 12-month extension study. Participants randomised to continue current dose for the first 12 months began allopurinol DE at month 12 if SU was ≥6 mg/dL (control/DE). Immediate DE participants who achieved target SU maintained allopurinol dose (DE/DE). The primary endpoints were reduction in SU and adverse events (AEs) at month 24.ResultsThe mean (SE) change in SU from month 12 to 24 was −1.1 (0.2) mg/dL in control/DE and 0.1 (0.2) mg/dL in DE/DE group (p<0.001). There was a significant reduction in the percentage of individuals having a gout flare in the month prior to months 12 and 24 compared with baseline in both groups and in mean tophus size over 24 months, but no difference between randomised groups. There were similar numbers of AEs and serious adverse events between groups.ConclusionsThe majority of people with gout tolerate higher than creatinine clearance-based allopurinol dose and achieve and maintain target SU. Slow allopurinol DE may be appropriate in clinical practice even in those with kidney impairment.Trial registration numberACTRN12611000845932

scholarly journals A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Daniel J. Lovell ◽  
Jason A. Dare ◽  
Megan Francis-Sedlak ◽  
Julie Ball ◽  
Brian D. LaMoreaux ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Fixed Dose ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Adolescent Patients
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