scholarly journals Trimethoprim-sulfamethoxazole Versus Azithromycin for the Treatment of Undifferentiated Febrile Illness in Nepal: A Double-blind, Randomized, Placebo-controlled Trial

2020 ◽  
Author(s):  
Abhishek Giri ◽  
Abhilasha Karkey ◽  
Sabina Dangol ◽  
Amit Arjyal ◽  
Sunil Pokharel ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Enteric Fever ◽  
Controlled Trial ◽  
Febrile Illness ◽  
Blood Cultures ◽  
Clearance Time ◽  
Double Blind ◽  
Fever Clearance Time ◽  
Secondary Endpoints ◽  
Fever Treatment

Abstract Background Azithromycin and trimethoprim-sulfamethoxazole (SXT) are widely used to treat undifferentiated febrile illness (UFI). We hypothesized that azithromycin is superior to SXT for UFI treatment, but the drugs are noninferior to each other for culture-confirmed enteric fever treatment. Methods We conducted a double-blind, randomized, placebo-controlled trial of azithromycin (20 mg/kg/day) or SXT (trimethoprim 10 mg/kg/day plus sulfamethoxazole 50 mg/kg/day) orally for 7 days for UFI treatment in Nepal. We enrolled patients >2 years and <65 years of age presenting to 2 Kathmandu hospitals with temperature ≥38.0°C for ≥4 days without localizing signs. The primary endpoint was fever clearance time (FCT); secondary endpoints were treatment failure and adverse events. Results From June 2016 to May 2019, we randomized 326 participants (163 in each arm); 87 (26.7%) had blood culture–confirmed enteric fever. In all participants, the median FCT was 2.7 days (95% confidence interval [CI], 2.6–3.3 days) in the SXT arm and 2.1 days (95% CI, 1.6–3.2 days) in the azithromycin arm (hazard ratio [HR], 1.25 [95% CI, .99–1.58]; P = .059). The HR of treatment failures by 28 days between azithromycin and SXT was 0.62 (95% CI, .37–1.05; P = .073). Planned subgroup analysis showed that azithromycin resulted in faster FCT in those with sterile blood cultures and fewer relapses in culture-confirmed enteric fever. Nausea, vomiting, constipation, and headache were more common in the SXT arm. Conclusions Despite similar FCT and treatment failure in the 2 arms, significantly fewer complications and relapses make azithromycin a better choice for empirical treatment of UFI in Nepal. Clinical Trials Registration NCT02773407.

scholarly journals Efficacy of artemether-lumefantrine and artesunate-amodiaquine for treating uncomplicated falciparum malaria in children

2012 ◽  
Vol 52 (5) ◽  
pp. 260
Author(s):  
Tri Faranita ◽  
Ayodhia Pitaloka Pasaribu ◽  
Muhammad Ali ◽  
Munar Lubis ◽  
Syahril Pasaribu
Keyword(s):  
Treatment Failure ◽  
Falciparum Malaria ◽  
Controlled Trial ◽  
Parasite Clearance ◽  
Uncomplicated Falciparum Malaria ◽  
Clearance Time ◽  
Parasite Clearance Time ◽  
Fever Clearance Time ◽  
Late Treatment ◽  
Cure Rates

Background Artesunate-amodiaquine (ASAQ) has been usedas a firsdine treatment for uncomplicated faldparum malariain Indonesia since 2004. Its efficacy depends on amodiaquineresistance of the infecting parasites. Artemether-lumefantrine(AL) has been shown to be highly efficacious in treatinguncomplicated faldparum malaria in several countries. However,there have been few studies on these anti-malarial medicationsin Indonesia.Objective To compare the efficacy of AL to ASAQ for treatinguncomplicated faldparum malaria in children.Methods An open, randomized, controlled trial wasconducted in school-aged children in the Mandailing NatalRegency, North Sumatera Province, Indonesia, from Octoberto December 2010. A total of 280 pediatric, uncomplicatedfalciparum malaria patients were randomly assigned to receiveeither AL or ASAQ for 3 days. Participants were followed-up ondays 1,2,3,7, 14, 28 and 42 following the first medication dose.The outcomes noted were adequate clinical and parasitologicalresponse (ACPR), parasite reduction, parasite clearance time,fever clearance time and adverse events. Analysis was basedon intention-to-treat.Results In this study, ACPRs on day 42 were 86.4% and 90.7%for the ASAQ and AL groups, respectively (p=0.260). On days 7and 14, the AL group had higher cure rates than that of the ASAQgroup (P<0.05). Early treatment failure, late treatment failure andparasitological failure for both groups were similar. We also foundfaster parasite clearance time and higher parasite reduction in theAL group than in the ASAQ group. However, fever clearancetime was shorter in the ASAQ group. The incidence of adverseevents such as nausea, vomiting, malaise, and pruritus were similarbetween the two groups (P=0.441).Conclusion AL had higher efficacy than ASAQ for the treatment of uncomplicated falciparum malaria in children.[Paediatr rndones. 2012;52:260-6].

scholarly journals Randomized, controlled trial of lasmiditan over four migraine attacks: Findings from the CENTURION study

Cephalalgia ◽  
2021 ◽  
Vol 41 (3) ◽  
pp. 294-304 ◽  
Author(s):  
Messoud Ashina ◽  
Uwe Reuter ◽  
Timothy Smith ◽  
Judith Krikke-Workel ◽  
Suzanne R Klise ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Study Drug ◽  
Statistical Testing ◽  
Control Group ◽  
Double Blind ◽  
Treatment Groups ◽  
Primary Endpoints ◽  
Registration Number ◽  
Secondary Endpoints ◽  
Common Teaes

Background We present findings from the multicenter, double-blind Phase 3 study, CENTURION. This study was designed to assess the efficacy of and consistency of response to lasmiditan in the acute treatment of migraine across four attacks. Methods Patients were randomized 1:1:1 to one of three treatment groups – lasmiditan 200 mg; lasmiditan 100 mg; or a control group that received placebo for three attacks and lasmiditan 50 mg for either the third or fourth attack. The primary endpoints were pain freedom at 2 h (first attack) and pain freedom at 2 h in ≥2/3 attacks. Secondary endpoints included pain relief, sustained pain freedom and disability freedom. Statistical testing used a logistic regression model and graphical methodology to control for multiplicity. Results Overall, 1471 patients treated ≥1 migraine attack with the study drug. Both primary endpoints were met for lasmiditan 100 mg and 200 mg ( p < 0.001). All gated secondary endpoints were met. The incidence of treatment-emergent adverse events (TEAEs) was highest during the first attack. The most common TEAEs with lasmiditan were dizziness, paresthesia, fatigue, and nausea; these were generally mild or moderate in severity. Conclusions These results confirm the early and sustained efficacy of lasmiditan 100 mg and 200 mg and demonstrate consistency of response across multiple attacks. Trial Registration Number: NCT03670810

Optimizing chair time in infusion centers using intravenous cetirizine premedication for the prevention of hypersensitivity infusion reactions.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13508-e13508
Author(s):  
Julio Antonio Peguero ◽  
Ahmed Ayad ◽  
Stacia Young-Wesenberg ◽  
Teresa Yang ◽  
Janine North ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Quality Care ◽  
Primary Objective ◽  
Double Blind ◽  
Acute Urticaria ◽  
Number Of Patients ◽  
Study Results ◽  
Secondary Endpoints ◽  
Infusion Reactions ◽  
Anti Cd20

e13508 Background: Oncology infusion centers are increasingly focused on improving operational efficiencies and patient satisfaction, while maintaining quality care. One key component is optimizing chair time, which has been especially important for patient safety during the COVID-19 pandemic to reduce risk of transmission. Many infusions require antihistamine premedication to reduce the risk of hypersensitivity infusion reactions (IRs). The two IV options are IV diphenhydramine and IV cetirizine, which have a quicker onset than oral options and can be administered IV push. In treating acute urticaria, IV cetirizine was shown to be comparable to IV diphenhydramine, with fewer side effects, and it may be effective for preventing IRs with improved chair time. Methods: A randomized, double-blind phase 2 study evaluating premedication with single dose IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 34 patients receiving paclitaxel, rituximab, its biosimilar or obinutuzumab (first cycle, retreatment after 6 months or with persistent IRs). The primary objective was the incidence of IRs after premedication. Secondary endpoints included sedation due to antihistamines and time to readiness for discharge. Sedation was reported by patients on a scale of 0-4 (0 = none to 4 = extremely severe). No formal statistical analyses were planned given the exploratory nature of the study. Results: Adults primarily with cancer (n = 31 [91%]) were enrolled during the COVID-19 pandemic, from March 25 to November 23, 2020. The median age was 65 and 67 years in the IV cetirizine and diphenhydramine groups, respectively. The number of patients with IRs was 2/17 (11.8%) with IV cetirizine versus 3/17 (17.6%) with IV diphenhydramine. The mean sedation score in the IV cetirizine group compared to the IV diphenhydramine group was lower at all time points, including at discharge (0.1 vs 0.4, respectively). Mean time to discharge was 24 minutes less with IV cetirizine (4.3 hours [1.5]) versus IV diphenhydramine (4.7 hours [1.2]). This difference was greater (30 minutes less) in those ≥65 years of age (4.4 [1.3] vs 4.9 [1.0] hours). Regardless of whether patients received paclitaxel (n = 9) or an anti-CD20 (n = 25), patients had less chair time when premedicated with IV cetirizine. There were fewer treatment-related adverse events (AEs) with IV cetirizine (2 events) than with IV diphenhydramine (4 events). Conclusions: This was the first randomized, controlled trial evaluating IV antihistamine premedication for IRs and chair time. It was shown that IV cetirizine can prevent IRs, with less sedation, fewer related AEs and reduced chair time compared to IV diphenhydramine. This improves infusion center operations and patient experience. Clinical trial information: NCT04189588.

scholarly journals Neurologic Safety of Etomidate-Based Sedation during Upper Endoscopy in Patients with Liver Cirrhosis Compared with Propofol: A Double-Blind, Randomized Controlled Trial

2020 ◽  
Vol 9 (8) ◽  
pp. 2424
Author(s):  
Jang Han Jung ◽  
Bomi Hyun ◽  
Jin Lee ◽  
Dong Hee Koh ◽  
Jung Hee Kim ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Cardiovascular Events ◽  
Controlled Trial ◽  
Early Discharge ◽  
Double Blind ◽  
Increased Risk ◽  
Overt Hepatic Encephalopathy ◽  
Secondary Endpoints ◽  
Number Connection Test ◽  
Severe Degree

(1) Background: Although etomidate-based sedation is an effective and safe protocol in endoscopic procedures, there is a lack of evidence regarding the safety of etomidate in patients with liver cirrhosis (LC). This study aimed to compare the neurologic safety and efficacy of etomidate and propofol for endoscopic sedation in patients with LC. (2) Methods: From December 2017 to December 2019, consecutive cirrhotic patients who underwent sedative endoscopy using either etomidate or propofol were randomly recruited. The primary endpoint was the number connection test (NCT), and the secondary endpoints included factors for the safety of sedatives during endoscopy. (3) Results: 63 patients were enrolled in each of the etomidate and propofol groups. The NCT times were significantly lower in the etomidate group than in the propofol group. Furthermore, severe or very severe degree of encephalopathy was higher in the propofol group but was not significantly different. Pharmacological properties and the overall incidence of respiratory and cardiovascular events did not differ significantly between the groups. (4) Conclusion: Etomidate-based sedation exacerbates neither subclinical nor overt hepatic encephalopathy. It guarantees efficacies similar to those of propofol regarding rapid sedation, fast recovery, and early discharge, with no increased risk of adverse respiratory or cardiovascular events in patients with LC.

scholarly journals Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial

Thorax ◽  
2019 ◽  
Vol 75 (1) ◽  
pp. 50-56 ◽  
Author(s):  
David Currow ◽  
Sandra Louw ◽  
Philip McCloud ◽  
Belinda Fazekas ◽  
John Plummer ◽  
...  
Keyword(s):  
Sustained Release ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Oral Morphine ◽  
Immediate Release ◽  
Morphine Group ◽  
Double Blind ◽  
Intention To Treat ◽  
Palliative Care Services ◽  
Secondary Endpoints

IntroductionMorphine may decrease the intensity of chronic breathlessness but data from a large randomised controlled trial (RCT) are lacking. This first, large, parallel-group trial aimed to test the efficacy and safety of regular, low-dose, sustained-release (SR) morphine compared with placebo for chronic breathlessness.MethodsMultisite (14 inpatient and outpatient cardiorespiratory and palliative care services in Australia), parallel-arm, double-blind RCT. Adults with chronic breathlessness (modified Medical Research Council≥2) were randomised to 20 mg daily oral SR morphine and laxative (intervention) or placebo and placebo laxative (control) for 7 days. Both groups could take ≤6 doses of 2.5 mg, ‘as needed’, immediate-release morphine (≤15 mg/24 hours) as required by the ethics review board. The primary endpoint was change from baseline in intensity of breathlessness now (0–100 mm visual analogue scale; two times per day diary) between groups. Secondary endpoints included: worst, best and average breathlessness; unpleasantness of breathlessness now, fatigue; quality of life; function; and harms.ResultsAnalysed by intention-to-treat, 284 participants were randomised to morphine (n=145) or placebo (n=139). There was no difference between arms for the primary endpoint (mean difference −0.15 mm (95% CI −4.59 to 4.29; p=0.95)), nor secondary endpoints. The placebo group used more doses of oral morphine solution during the treatment period (mean 8.7 vs 5.8 doses; p=0.001). The morphine group had more constipation and nausea/vomiting. There were no cases of respiratory depression nor obtundation.ConclusionNo differences were observed between arms for breathlessness, but the intervention arm used less rescue immediate-release morphine.Trial registration numberACTRN12609000806268.

A randomized, double-blind trial of fluorouracil plus placebo versus fluorouracil plus oral leucovorin in patients with metastatic colorectal cancer.

1993 ◽  
Vol 11 (10) ◽  
pp. 1888-1893 ◽  
Author(s):  
L R Laufman ◽  
R M Bukowski ◽  
M A Collier ◽  
B A Sullivan ◽  
R A McKinnis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Failure ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Controlled Trial ◽  
Double Blind ◽  
Time To Treatment Failure ◽  
To Receive ◽  
Toxicity Pattern

PURPOSE A prospectively randomized trial was performed to determine whether the combination of fluorouracil (FU) plus leucovorin (FU-LV) administered orally is more effective than equitoxic FU for patients with metastatic colorectal cancer. PATIENTS AND METHODS A double-blind, placebo-controlled trial design was used to eliminate observer bias. An escalating FU dosing schedule was used to achieve equal toxicity. End points were response, time to treatment failure (TTF), and eight quality-of-life (QL) parameters. A crossover arm allowed FU-treated patients to receive FU-LV combination treatment after treatment failure. RESULTS Response rate was 32% for FU-LV versus 23% for FU (P = .15). Median TTF was 22 versus 16 weeks (P = .27). Median survival time was 44 versus 54 weeks (P = .26). QL was the same for both treatments, except for days of hospitalization, which was greater for FU-LV (P < .001). Toxicities were similar to those previously reported for FU-LV and FU alone. CONCLUSION Oral LV-FU produces the same efficacy and toxicity pattern as has been reported for intravenous LV-FU. When FU-LV is compared with equitoxic doses of FU, there is no difference in patient outcome. These results suggest that patients with advanced disease should receive FU at doses adequate to produce toxicity.

A randomized, controlled trial of fingolimod (FTY720) in Japanese patients with multiple sclerosis

2012 ◽  
Vol 18 (9) ◽  
pp. 1269-1277 ◽  
Author(s):  
T Saida ◽  
S Kikuchi ◽  
Y Itoyama ◽  
Q Hao ◽  
T Kurosawa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Phase Ii ◽  
Clinical Efficacy ◽  
Controlled Trial ◽  
Japanese Patients ◽  
Double Blind ◽  
Parallel Group ◽  
Safety Outcomes ◽  
Secondary Endpoints ◽  
Caucasian Patients

Background: Fingolimod (FTY720) has previously shown clinical efficacy in phase II/III studies of predominantly Caucasian populations with multiple sclerosis (MS). Objectives: To report six-month efficacy and safety outcomes in Japanese patients with relapsing MS treated with fingolimod. Methods: In this double-blind, parallel-group, phase II study, 171 Japanese patients with relapsing MS were randomized to receive once-daily fingolimod 0.5 mg or 1.25 mg, or matching placebo for six months. The primary and secondary endpoints were the percentages of patients free from gadolinium (Gd)-enhanced lesions at months 3 and 6, and relapses over six months, respectively; safety outcomes were also assessed. Results: 147 patients completed the study. Higher proportions of patients were free from Gd-enhanced lesions at months 3 and 6 with fingolimod (0.5 mg: 70%, p = 0.004; 1.25 mg: 86%, p < 0.001) than with placebo (40%). Odds ratios for the proportions of relapse-free patients over six months favoured fingolimod versus placebo but were not significant. Adverse events related to fingolimod included transient bradycardia and atrioventricular block at treatment initiation, and elevated liver enzyme levels. Conclusions: This study demonstrated the clinical efficacy of fingolimod for the first time in Japanese patients with MS, consistent with the established effects of fingolimod in Caucasian patients.

scholarly journals 2226. Impact of Prior and Concomitant Antibacterial Therapy on Outcomes in the ASPECT-NP Randomized, Controlled Trial of Ceftolozane/Tazobactam (C/T) vs. Meropenem (MEM) in Patients with Ventilated Nosocomial Pneumonia (NP)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S760-S760
Author(s):  
Richard G Wunderink ◽  
Christopher Bruno ◽  
Ignacio Martin-Loeches ◽  
Marin Kollef ◽  
Jean-Francois Timsit ◽  
...  
Keyword(s):  
Antibacterial Therapy ◽  
Controlled Trial ◽  
Treatment Options ◽  
Study Drug ◽  
Drug Susceptibility ◽  
Double Blind ◽  
Gram Negative ◽  
Randomized Controlled ◽  
Secondary Endpoints ◽  
The Impact

Abstract Background NP is a frequent healthcare-acquired infection associated with high mortality; rising resistance rates among causative Gram-negative pathogens require new treatment options. In the randomized, controlled, double-blind, phase 3 ASPECT-NP trial, C/T (at double the initially approved dose) was noninferior to MEM for ventilated NP in both primary and key secondary endpoints. Here we evaluate the impact of prior and concomitant Gram-negative antibacterial therapy on outcomes in that trial. Methods Mechanically ventilated patients with ventilator-associated or hospital-acquired pneumonia were randomized 1:1 to 3 g C/T or 1 g MEM, both by 1-h IV infusion every 8 hours for 8–14 days. Patients could receive ≤24 hours of active antibacterial therapy within ≤72 hours prior to first dose; longer durations were permitted in case of prior treatment failure (i.e., signs and/or symptoms of the current episode of ventilated NP persisted/worsened despite ≥48 hours of treatment). At sites with MEM-resistant Pseudomonas aeruginosa rates ≥15%, patients could optionally receive up to 72 h of adjunctive empiric aminoglycoside (amikacin was recommended) until study drug susceptibility was confirmed. Primary and key secondary endpoints, respectively, were 28-d all-cause mortality and clinical response at test of cure (TOC; 7–14 days after the end of therapy) in the intent to treat (ITT) population (all randomized patients). Results In the C/T arm, 285/362 (79%) ITT patients received prior systemic Gram-negative therapy and 103/362 (28%) received adjunctive aminoglycoside, compared with 288/364 (79%) and 112/364 (31%) patients, respectively, in the MEM arm. In the microbiologic ITT population, causative pathogens in patients failing prior therapy at the time of enrollment (C/T 15%, MEM 11%) were mainly Klebsiella spp (33%), P. aeruginosa (17%), Escherichia coli (14%), and Acinetobacter baumannii (8%). Mortality and cure rates were comparable between C/T and MEM regardless of receipt of prior systemic or adjunctive Gram-negative therapy (table). Conclusion Prior and adjunctive Gram-negative antibacterial therapy did not affect the relative efficacy of C/T (at the 3-g dose) vs. MEM in these high-risk patients with Gram-negative ventilated NP. Disclosures All authors: No reported disclosures.

scholarly journals Pharmaceutical-grade Chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT)

2017 ◽  
Vol 76 (9) ◽  
pp. 1537-1543 ◽  
Author(s):  
Jean-Yves Reginster ◽  
Jean Dudler ◽  
Tomasz Blicharski ◽  
Karel Pavelka
Keyword(s):  
Placebo Group ◽  
Knee Osteoarthritis ◽  
Chondroitin Sulfate ◽  
Controlled Trial ◽  
European Medicines Agency ◽  
Double Blind ◽  
Knee Oa ◽  
Symptomatic Knee Osteoarthritis ◽  
Symptomatic Knee ◽  
Secondary Endpoints

ObjectivesChondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis consistent with the European Medicines Agency guideline.MethodsA prospective, randomised, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day)-controlled trial assessing changes in pain on a Visual Analogue Scale (VAS) and in the Lequesne Index (LI) as coprimary endpoints. Minimal-Clinically Important Improvement (MCII), Patient-Acceptable Symptoms State (PASS) were used as secondary endpoints.Results604 patients (knee osteoarthritis) diagnosed according to American College of Rheumalogy (ACR) criteria, recruited in five European countries and followed for 182 days. CS and celecoxib showed a greater significant reduction in pain and LI than placebo. In the intention-to-treat (ITT) population, pain reduction in VAS at day 182 in the CS group (−42.6 mm) and in celecoxib group (−39.5 mm) was significantly greater than the placebo group (−33.3 mm) (p=0.001 for CS and p=0.009 for celecoxib), while no difference observed between CS and celecoxib. Similar trend for the LI, as reduction in this metric in the CS group (−4.7) and celecoxib group (−4.6) was significantly greater than the placebo group (−3.7) (p=0.023 for CS and p=0.015 for celecoxib), no difference was observed between CS and celecoxib. Both secondary endpoints (MCII and PASS) at day 182 improved significantly in the CS and celecoxib groups. All treatments demonstrated excellent safety profiles.ConclusionA 800 mg/day pharmaceutical-grade CS is superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in symptomatic knee osteoarthritis (OA) patients. This formulation of CS should be considered a first-line treatment in the medical management of knee OA.

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