scholarly journals Once-Daily, Controlled-Release Tramadol and Sustained-Release Diclofenac Relieve Chronic Pain due to Osteoarthritis: A Randomized Controlled Trial

2008 ◽  
Vol 13 (2) ◽  
pp. 103-110 ◽  
Author(s):  
André D Beaulieu ◽  
Paul M Peloso ◽  
Boulos Haraoui ◽  
William Bensen ◽  
Glen Thomson ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Controlled Release ◽  
Side Effects ◽  
Adverse Events ◽  
Sustained Release ◽  
Controlled Trial ◽  
Hip Osteoarthritis ◽  
Visual Analogue Scale Pain ◽  
Serious Adverse Events ◽  
Once Daily

OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR) tramadol and sustained-release (SR) diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees.METHODS: Patients with at least moderate pain intensity, and having received analgesics over the past three months, underwent a two-to seven-day washout of current analgesics before initiation of 200 mg CR tramadol or 75 mg SR diclofenac. During the eight-week study, patients returned to the clinic biweekly. CR tramadol doses were titrated to a maximum of 200 mg, 300 mg or 400 mg per day. SR diclofenac doses were titrated to 75 mg or 100 mg once daily, or 75 mg twice a day based on pain relief and the presence of side effects. For rescue analgesic, patients took acetaminophen as needed, up to 650 mg three times a day.RESULTS: Forty-five patients on CR tramadol and 52 patients on SR diclofenac were evaluable. Significant improvements from prestudy treatment were shown for visual analogue scale pain (P=0.0001), stiffness (P<0.0005) and physical function (P=0.0001) scores for both treatments. There were no significant differences between the two treatments in the Western Ontario and McMaster Universities subscales, overall pain, pain and sleep, or the clinical effectiveness evaluation. Overall incidence of adverse events was similar in both groups, with more opioid-related adverse events with CR tramadol, and two serious adverse events occurring with the use of SR diclofenac.CONCLUSIONS: CR tramadol is as effective as SR diclofenac in the treatment of pain due to knee or hip osteoarthritis, with the potential for fewer of the serious side effects that characterize nonsteroidal anti-inflammatory drug administration.

scholarly journals EarLy Exercise in blunt Chest wall Trauma: a feasibility trial (ELECT Trial)

2020 ◽  
Author(s):  
Ceri Battle ◽  
Claire O'Neill ◽  
Hannah Toghill ◽  
Luke Newey ◽  
Hayley Hutchings
Keyword(s):  
Chronic Pain ◽  
Adverse Events ◽  
Chest Wall ◽  
Controlled Trial ◽  
Shoulder Girdle ◽  
University Teaching ◽  
Feasibility Trial ◽  
Serious Adverse Events ◽  
Early Exercise ◽  
Chest Wall Trauma

Abstract Background For patients with blunt chest wall trauma, no evidence exists regarding the optimal physiotherapy treatment aimed at addressing the longer-term complications, specifically chronic pain and disability. The overall aim of this phase of work, is to investigate whether early thoracic and shoulder girdle exercises improve chronic pain in patients with blunt chest wall trauma, when compared to normal care. Methods A single centre, parallel, feasibility randomised controlled trial was completed at a University Teaching Hospital in Wales. Adult patients with blunt chest wall trauma, admitted to hospital for greater than 24 hours, with no concurrent, immediately life-threatening injuries, were included. The intervention was a simple physiotherapy programme comprising thoracic and shoulder girdle exercises. Feasibility outcome measures included: Primary: 1) adherence to the protocol by the physiotherapy team (more than 80% of eligible patients randomised), and 2) acceptability of the intervention by the patients (less than 30% of patients dissented to participation). Secondary: 1) ability to retrieve follow up data (response rate of more than 70% of participants) and, 2) safety of the intervention compared to routine care (no more than 10% increase in serious adverse events). Results 14 patients were recruited to the trial. Clinicians randomised 100% of eligible patients during the trial period. All feasibility criteria were fully met. The intervention was safe the number of serious adverse events was comparable between the control and intervention periods. Discussion We have demonstrated that a fully powered randomised clinical trial of the ELECT Trial is feasible. Minor methodological modifications will be made for the full trial. ISRCTN Trial registration number ISRCTN 16197429

scholarly journals Randomized Controlled Trial of Sequential Intravenous (i.v.) and Oral Moxifloxacin Compared with Sequential i.v. and Oral Co-Amoxiclav with or without Clarithromycin in Patients with Community-Acquired Pneumonia Requiring Initial Parenteral Treatment

2002 ◽  
Vol 46 (6) ◽  
pp. 1746-1754 ◽  
Author(s):  
R. Finch ◽  
D. Schürmann ◽  
O. Collins ◽  
R. Kubin ◽  
J. McGivern ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Success ◽  
Controlled Trial ◽  
Community Acquired Pneumonia ◽  
Combination Regimen ◽  
Success Rates ◽  
Serious Adverse Events ◽  
Once Daily ◽  
Comparator Group ◽  
Present Trial

ABSTRACT The objective of the present trial was to compare the efficacy, safety, and tolerability of moxifloxacin (400 mg) given intravenously (i.v.) once daily followed by oral moxifloxacin (400 mg) for 7 to 14 days with the efficacy, safety, and tolerability of co-amoxiclav (1.2 g) administered by i.v. infusion three times a day followed by oral co-amoxiclav (625 mg) three times a day, with or without clarithromycin (500 mg) twice daily (i.v. or orally), for 7 to 14 days in adult patients with community-acquired pneumonia requiring initial parenteral therapy. A total of 628 patients were enrolled and assessed by evaluation of their clinical and bacteriological responses 5 to 7 days and 21 to 28 days after administration of the last dose of study medication. Although the trial was designed, on the basis of predefined outcomes, to demonstrate the equivalence of the two regimens, the results showed statistically significant higher clinical success rates (for moxifloxacin, 93.4%, and for comparator regimen, 85.4%; difference [Δ], 8.05%; 95% confidence interval [CI], 2.91 to 13.19%; P = 0.004) and bacteriological success rates (for moxifloxacin, 93.7%, and for comparator regimen, 81.7%; Δ, 12.06%; 95% CI, 1.21 to 22.91%) for patients treated with moxifloxacin. This superiority was seen irrespective of the severity of the pneumonia and whether or not the combination therapy included a macrolide. The time to resolution of fever was also statistically significantly faster for patients who received moxifloxacin (median time, 2 versus 3 days), and the duration of hospital admission was approximately 1 day less for patients who received moxifloxacin. The treatment was converted to oral therapy immediately after the initial mandatory 3-day period of i.v. administration for a larger proportion of patients in the moxifloxacin group than patients in the comparator group (151 [50.2%] versus 57 [17.8%] patients). There were fewer deaths (9 [3.0%] versus 17 [5.3%]) and fewer serious adverse events (38 [12.6%] versus 53 [16.5%]) in the moxifloxacin group than in the comparator group. The rates of drug-related adverse events were comparable in both groups (38.9% in each treatment group). The overall incidence of laboratory abnormalities was similar in both groups. Thus, it is concluded that monotherapy with moxifloxacin is superior to that with a standard combination regimen of a β-lactam and a β-lactamase inhibitor, co-amoxiclav, with or without a macrolide, clarithromycin, in the treatment of patients with community-acquired pneumonia admitted to a hospital.

scholarly journals 1288. Phase 1 First-in-Human Single- and Multiple-Ascending Dose Trial Demonstrates Pharmacokinetics (PK) and Tolerability of SPR720, an Oral DNA GyrB Inhibitor for Mycobacterial Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S659-S659
Author(s):  
Angela Talley ◽  
Archie Thurston ◽  
Grayson Moore ◽  
Myriah M Satterfield ◽  
Erika L Manyak ◽  
...  
Keyword(s):  
Adverse Events ◽  
Healthy Volunteers ◽  
Controlled Trial ◽  
Phase 1 ◽  
Safety Data ◽  
Elderly Subjects ◽  
Independent Contractor ◽  
Serious Adverse Events ◽  
Healthy Elderly ◽  
Dose Proportional

Abstract Background SPR720 (phosphate pro-drug of SPR719) is a novel aminobenzimidazole bacterial DNA gyrase (GyrB) inhibitor in development for non-tuberculous mycobacterial lung disease (NTM-LD) and pulmonary tuberculosis. SPR719 has broad-spectrum activity versus clinically relevant mycobacteria in vitro and in murine and hollow fiber (HF) infection models. In this first-in-human single ascending dose (SAD) /multiple ascending dose (MAD) study, the safety, tolerability and pharmacokinetics (PK) of SPR720/SPR719 were evaluated in healthy volunteers. Methods This was a Phase 1 randomized, double-blind, placebo-controlled trial with 7 SAD cohorts (including a food effect cohort) and 5 MAD cohorts. Healthy volunteers (n=8/cohort, 3:1 randomization) received SPR720 or placebo in single oral doses of ranging from 100 mg to 2000 mg or repeat total daily doses ranging from 500 mg to 1500 mg for 7 or 14 days. Safety monitoring and PK sampling occurred throughout the trial. Plasma and urine concentrations of SPR720/SPR719 were measured by validated LC-MS/MS methods. PK parameters were calculated using non-compartmental analysis. Results A total of 96 subjects (including 8 healthy elderly subjects, age ≥ 65 years) were randomized and received study drug. SPR720 was well-tolerated at daily doses up to 1000 mg for up to 14 days. Across SAD/MAD cohorts, the most common adverse events were gastrointestinal (nausea, vomiting and diarrhea) and headache, all of mild or moderate severity and dose dependent. No serious adverse events were reported. Across SAD cohorts, a dose proportional and greater-than-dose proportional increase in SPR719 plasma Cmax and AUC0-24, respectively were observed. SPR720 was rapidly absorbed with a mean SPR719 t1/2 of 2.9-4.5 h. Dosing with food decreased SPR719 plasma AUC by ~20%. No clinically meaningful effect of age on plasma AUC was observed. In the MAD cohorts, SPR719 plasma exposure declined approximately 40% between Day 1 and Day 7, suggesting induction of an elimination pathway. However, plasma AUC0-24 was similar at Days 7 and 14. Conclusion Together with HF pharmacodynamic data, human PK and safety data for SPR720 suggest that predicted therapeutic exposures can be attained with a well-tolerated once-daily dose. Further evaluation in a Phase 2 NTM-LD trial is planned. Disclosures Angela Talley, MD, Spero Therapeutics (Employee, Shareholder) Archie Thurston, Jr., PhD, Spero Therapeutics (Consultant) Grayson Moore, BA, RN, Spero Therapeutics, Inc. (Shareholder, Independent Contractor) Vipul Kumar, PhD, Spero Therapeutics (Employee, Shareholder) Suzanne Stokes, PhD, Spero Therapeutics (Employee, Shareholder) Aaron Dane, MSc, Spero theraputics (Consultant) David Melnick, MD, Spero Therapeutics (Employee)Spero Therapeutics (Employee)

Once-Daily Treatment for Mixed Anxiety/Depressive States: A Comparison of Slow Release Amitriptyline and Fluphenazine with Nortriptyline

1977 ◽  
Vol 5 (2) ◽  
pp. 109-113 ◽  
Author(s):  
R V Magnus ◽  
A A Schiff
Keyword(s):  
Side Effects ◽  
Sustained Release ◽  
Slow Release ◽  
Anxiolytic Effect ◽  
Daily Treatment ◽  
Dry Mouth ◽  
Double Blind ◽  
Once Daily ◽  
Therapeutic Advantage ◽  
Depressive States

Patients suffering from mixed anxiety/depressive states referred to a psychiatric out-patient clinic completed a four week course of either a once-daily tablet of 30 mg nortriptyline with 1· 5 mg fluphenazine, or a sustained release capsule of 50 mg amitriptyline once daily, on a double-blind basis. Depression improved satisfactorily on either treatment, but there was a greater reduction of anxiety on fluphenazine/nortriptyline. Drowsiness, however, occurred more frequently among the patients on amitriptyline, suggesting the sedative properties of this drug did not substitute adequately for a specific anxiolytic effect. Dry mouth was also noticeably more frequent with amitriptyline. As might be expected on pharmacokinetic and physiological grounds, the results suggest that the sustained release characteristics of the amitriptyline preparation lead to a maximization of side-effects during the day without conferring any therapeutic advantage.

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 Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial

2021 ◽  
Author(s):  
Kathryn E. Stephenson ◽  
Boris Julg ◽  
C. Sabrina Tan ◽  
Rebecca Zash ◽  
Stephen R. Walsh ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Adverse Events ◽  
Antiviral Activity ◽  
Controlled Trial ◽  
Phase 1 ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Cell Counts ◽  
Hiv 1

AbstractHuman immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg–1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg–1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.

A Controlled Trial of Extended-Release Guanfacine and Psychostimulants on Executive Function and ADHD

2018 ◽  
Vol 24 (2) ◽  
pp. 318-325 ◽  
Author(s):  
Judy P. M. van Stralen
Keyword(s):  
Executive Function ◽  
Adverse Events ◽  
Extended Release ◽  
Rating Scale ◽  
Controlled Trial ◽  
Severity Of Illness ◽  
P Value ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Stimulant Therapy

Objective: To evaluate the effectiveness of guanfacine extended-release (GXR) versus placebo as adjunct therapy to usual care stimulant therapy in improving executive function in children aged 6 to 12 years diagnosed with ADHD. Method: In this single center, double-blind placebo-controlled crossover trial, subjects continued to take their psychostimulant and were randomly assigned at baseline to receive active treatment or placebo first. Efficacy measures included Behavioural Rating Inventory of Executive Function (BRIEF-P), ADHD Rating Scale IV (ADHD-RS IV), and Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) scales. Safety measures included adverse events and vital signs. Results: Significant benefits of GXR plus psychostimulant were observed on BRIEF-P ( p value = .0392), ADHD-RS-IV ( p < .0001), CGI-S ( p = .0007), and CGI-I ( p = .003). There were no serious adverse events and no new safety signals. Conclusion: Use of GXR as adjunctive therapy to stimulant therapy significantly improves executive function in children with ADHD.

Effectiveness of enteral ivabradine for heart rate control in septic shock: A randomised controlled trial

2021 ◽  
pp. 0310057X2110099
Author(s):  
Priyankar K Datta ◽  
Vimi Rewari ◽  
Rashmi Ramachandran ◽  
Preet M Singh ◽  
Bikash R Ray ◽  
...  
Keyword(s):  
Heart Rate ◽  
Septic Shock ◽  
Adverse Events ◽  
Standard Therapy ◽  
Controlled Trial ◽  
Cardiac Pacemaker ◽  
Stroke Volume Index ◽  
Volume Index ◽  
Serious Adverse Events ◽  
Group I

Persistent tachycardia in patients with septic shock predicts poor outcome. This study sought to investigate the effect of the cardiac pacemaker current inhibitor ivabradine on heart rate and cardio-circulatory function in patients with septic shock. After informed consent, 60 patients with septic shock and persistent tachycardia (heart rate >95 /minute) were prospectively randomly assigned to receive either standard therapy for septic shock (group S) or standard therapy along with enteral ivabradine (group I) for the initial 96 hours after enrolment. Primary outcome was the difference in heart rate between the two groups during the first 96 hours. Secondary outcomes included the effect of ivabradine on haemodynamic, oxygenation, myocardial function and organ function parameters, incidence of adverse events and 30-day overall survival. Heart rate was lower in group I compared to group S (median difference in area under the curve –25.6 (95% confidence intervals –31.4 to –15.9) /minute; P <0.001). Vasopressor requirements, blood lactate levels, Sequential Organ Failure Assessment scores and E/e′ ratio were lower in group I compared to group S. Stroke volume index and ejection fraction were higher in group I while cardiac index and oxygen delivery parameters were maintained similar to group S. There was no difference in 30-day mortality or in the incidence of serious adverse events. Enteral ivabradine is effective in reducing heart rate, and improving haemodynamic parameters and cardiac function in patients with septic shock and persistent tachycardia, without increasing the incidence of adverse events.

A Practical Approach to the Use of Acitretin for the Treatment of Psoriasis

2010 ◽  
Vol 16a (2) ◽  
pp. 62-68
Author(s):  
Tina Bhutani ◽  
Kristine Busse
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Plaque Psoriasis ◽  
Practical Approach ◽  
Serious Adverse Events ◽  
Oral Retinoid ◽  
Systemic Agents ◽  
Term Maintenance

This clinical review outlines a practical approach to the use of acitretin in the treatment of psoriasis. Acitretin is approved by the Food and Drug Administration for the treatment of adult patients with chronic moderate to severe plaque psoriasis. It is an oral retinoid and is the only systemic agent that is not clinically immunosuppressive; it works primarily by enhancing differentiation and maturation of cells. Side effects associated with this medication are usually mild and manageable; serious adverse events are rare. Therefore, it can be used for long-term maintenance therapy or in combination with other topical or systemic agents and phototherapy.

Escitalopram versus risperidone for the treatment of behavioral and psychotic symptoms associated with Alzheimer's disease: a randomized double-blind pilot study

2011 ◽  
Vol 23 (9) ◽  
pp. 1515-1519 ◽  
Author(s):  
Yoram Barak ◽  
Igor Plopski ◽  
Shelly Tadger ◽  
Diana Paleacu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Events ◽  
Controlled Trial ◽  
Treated Group ◽  
Psychotic Symptoms ◽  
Completion Rates ◽  
Double Blind ◽  
Once Daily ◽  
Risperidone Group

ABSTRACTBackground: Antipsychotics are frequently used to treat psychosis, aggression and agitation in patients with Alzheimer's disease (AD), but safety warnings abound. Escitalopram was investigated since citalopram has demonstrated some effectiveness in AD. We compared escitalopram and risperidone for psychotic symptoms and agitation associated with AD.Methods: Inpatients with AD, who had been hospitalized because of behavioral symptoms, were recruited to a six-week randomized, double-blind, controlled trial. Participants (n = 40) were randomized to once daily risperidone 1 mg or escitalopram 10 mg.Results: The NPI total score improved in both groups. Onset was earlier in the risperidone-treated group, but improvement did not significantly differ between groups by study end. Completion rates differed for escitalopram (75%) and risperidone (55%), mainly due to adverse events. There were no adverse events in the escitalopram group, while in the risperidone group two patients suffered severe extrapyramidal symptoms and four patients suffered acute physical illness necessitating transfer to general hospital.Conclusion: Escitalopram and risperidone did not differ in efficacy in reducing psychotic symptoms and agitation in patients with AD. Completion rates were higher for escitalopram-treated patients. Replication in larger trials with ambulatory patients is needed.

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