Topical Ketoprofen Patch (100 mg) for the Treatment of Ankle Sprain: A Randomized, Double-Blind, Placebo-Controlled Study

Background Topical nonsteroidal anti-inflammatory drugs offer the advantage of enhanced drug delivery to local affected tissues with low plasma levels and an expected reduced incidence of systemic adverse events (mainly peptic ulcer disease and gastrointestinal hemorrhage). Hypothesis To test the efficacy and tolerability of a 100-mg patch of ketoprofen applied once a day. Study Design Randomized controlled clinical trial; Level of evidence, 1. Methods The 2-week trial included patients suffering painful (spontaneous pain ≥50 mm on a 0- to 100-mm visual analog scale), benign (grade I or II), recent (<2 days) ankle sprains as a model of general traumatic soft tissue injuries. The primary efficacy criterion was spontaneous pain change after 7 days of treatment in the intention-to-treat population. One hundred sixty-three patients were randomized (ketoprofen, 81; placebo, 82). Results After 1 week of treatment, the decrease in spontaneous pain was -50 ± 20 mm for ketoprofen and -38 ± 24 mm for the placebo, showing a statistically significant intergroup difference (P =. 0007). The majority of the secondary criteria were also statistically significant in favor of the ketoprofen patch. Tolerance was good in both groups, adverse events being mostly local. Conclusion This trial suggested that a 7-day course of treatment with a ketoprofen patch is useful in benign ankle sprain, without revealing unexpected adverse events.

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A Combination of Lactoplantibacillus plantarum Strains CECT7527, CECT7528 and CECT7529 Plus Monacolin K Reduces Blood Cholesterol: Results from a Randomized, Double-Blind, Placebo-Controlled Study

Nutrients ◽

10.3390/nu13041206 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1206

Author(s):

Rafael Guerrero-Bonmatty ◽

Guadalupe Gil-Fernández ◽

Francisco José Rodríguez-Velasco ◽

Jordi Espadaler-Mazo

Keyword(s):

Intervention Group ◽

Study Groups ◽

Statin Treatment ◽

Blood Cholesterol ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Red Yeast Rice ◽

Monacolin K ◽

Double Blind ◽

History Of

Background: Dietary supplements have been proposed to help manage blood cholesterol, including red yeast rice (RYR) extracts, plant sterols and stanols, beta-glucans, and some probiotics. This study was conducted to evaluate the efficacy of RYR (containing 10 mg of monacolin K) combined with 109 CFU of three Lactoplantibacillus plantarum strains (CECT7527, CECT7528, and CECT7529). Methods: A 12-week randomized, double-blinded, placebo-controlled clinical trial was conducted. In total, 39 adult patients were enrolled, having total cholesterol (TC) ≥200 mg/dL, and being statin-naïve or having recently stopped statin treatment because of intolerance. Active product or placebo were taken once daily, and subjects were evaluated at baseline, 6, and 12 weeks. Results: Study groups were comparable at baseline, except for history of recent hypercholesterolemia treatment (81% in active vs. 22% in placebo). Changes in LDL cholesterol and TC became significant compared to placebo (mean difference between groups and standard error of the mean = 23.6 ± 1.5 mg/dL, p = 0.023 and 31.4 ± 1.9 mg/dL, p = 0.011, respectively) upon adjusting for the baseline imbalance in hypercholesterolemia treatment. No adverse effects were noted during the study. Conclusion: This combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo, once adjusting for recent history of hypercholesterolemia treatment.

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Bilateral mandibular block improves pain relief and morphine consumption in mandibular osteotomies: a prospective, randomized, double-blind, placebo-controlled clinical trial

Regional Anesthesia and Pain Medicine ◽

10.1136/rapm-2020-102417 ◽

2021 ◽

Vol 46 (4) ◽

pp. 322-327

Author(s):

Marina Bertuit ◽

Francesca Rapido ◽

Habib Ly ◽

Charlotte Vannucci ◽

Jérôme Ridolfo ◽

...

Keyword(s):

Postoperative Analgesia ◽

Severe Pain ◽

Postoperative Nausea And Vomiting ◽

Sensory Innervation ◽

Morphine Consumption ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Block Group ◽

Double Blind ◽

Double Blind Placebo

BackgroundThe sensory innervation of the lower jaw mainly depends on the third root of the trigeminal nerve, the mandibular nerve (V3). The aim of this single-center, prospective, randomized, double-blind, placebo-controlled study was to evaluate the effectiveness of bilateral V3 block for postoperative analgesia management in mandibular osteotomies.Methods107 patients undergoing mandibular surgery (75 scheduled osteotomies and 32 mandible fractures) were randomized in two groups. A bilateral V3 block was performed in each group, either with ropivacaine 0.75% (block group, n=50) or with a placebo (placebo group, n=57). A postoperative multimodal analgesia was equally provided to both groups. The primary outcome was the cumulative morphine consumption at 24 hours. Secondary outcomes were the occurrence of severe pain and the incidence of postoperative nausea and vomiting (PONV) in the first 24 hours. Data were analyzed on an intention-to-treat basis.ResultsThe cumulative morphine consumption at 24 hours was significantly lower in the block group (median 8.0 mg (IQR 2.0–21.3) vs 12.0 mg (IQR 8.0–22.0), p=0.03), as well as the incidence of severe pain during the 24 hours of follow-up (4.0% vs 22.8%, p<0.01). The mandibular block had no impact on the incidence of PONV.ConclusionBilateral V3 block for mandibular osteotomies is an effective opioid-sparing procedure. It provided better postoperative analgesia in the first 24 hours, and it did not affect PONV incidence.Trial registration numberNCT02618993.

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A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

Vaccines ◽

10.3390/vaccines8020296 ◽

2020 ◽

Vol 8 (2) ◽

pp. 296

Author(s):

Irina Kiseleva ◽

Irina Isakova-Sivak ◽

Marina Stukova ◽

Marianna Erofeeva ◽

Svetlana Donina ◽

...

Keyword(s):

Adverse Events ◽

Influenza Vaccine ◽

Phase 1 ◽

Healthy Adults ◽

Controlled Study ◽

Temperature Sensitive ◽

Serious Adverse Events ◽

Double Blind ◽

Human Influenza Virus ◽

Live Attenuated Influenza Vaccine

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted.

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Rice Bran Supplement Containing A Functional Substance, the Novel Peptide Leu-Arg-Ala, has Anti-Hypertensive Effects: A Double-Blind, Randomized, Placebo-Controlled Study

Nutrients ◽

10.3390/nu11040726 ◽

2019 ◽

Vol 11 (4) ◽

pp. 726

Author(s):

Ogawa ◽

Shobako ◽

Fukuhara ◽

Satoh ◽

Kobayashi ◽

...

Keyword(s):

Blood Pressure ◽

Placebo Group ◽

Adverse Events ◽

Rice Bran ◽

Test Group ◽

Normal Blood ◽

Controlled Study ◽

The Novel ◽

Normal Blood Pressure ◽

Double Blind

The anti-hypertensive effect of processed rice bran (PRB) was recently reported, for which the novel peptide Leu-Arg-Ala (LRA) was identified as the functional substance. The purpose of this study was to assess the anti-hypertensive effects of a rice bran supplement containing PRB in individuals with high-normal blood pressure (systolic blood pressure (SBP): 130–139 mmHg and/or diastolic blood pressure (DBP): 85–89 mmHg) or grade 1 hypertension (SBP: 140–159 mmHg and/or DBP: 90–99 mmHg). One hundred individuals with high-normal blood pressure or grade 1 hypertension were recruited to participate in this double-blind, randomized, placebo-controlled study. Participants were randomly allocated to the placebo group (n = 50) or the test group (n = 50). Each group took four test tablets (43 μg LRA/day) or four placebo tablets daily. The decrease in blood pressure in the test group compared with the placebo group was the primary outcome. Adverse events were recorded and hematological/urinary parameters measured to determine the safety of the supplement, which was the secondary outcome. In total, 87 participants completed the study. The SBP of the test group at 12 weeks was significantly lower than that of the placebo group (p = 0.0497). No serious adverse events were observed. Daily consumption of a rice bran supplement containing PRB can safely improve mildly elevated blood pressure.

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Efficacy and safety of galcanezumab for prevention of migraine headache in Japanese patients with episodic migraine: A phase 2 randomized controlled clinical trial

Cephalalgia Reports ◽

10.1177/2515816320932573 ◽

2020 ◽

Vol 3 ◽

pp. 251581632093257 ◽

Cited By ~ 1

Author(s):

Fumihiko Sakai ◽

Akichika Ozeki ◽

Vladimir Skljarevski

Keyword(s):

Migraine Headache ◽

Japanese Patients ◽

Episodic Migraine ◽

Secondary Outcome ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Life Questionnaire ◽

Efficacy And Safety ◽

Double Blind ◽

Secondary Endpoints

Objective: This study was designed to assess the efficacy and safety of galcanezumab in comparison with placebo for the prevention of migraine in Japanese patients with episodic migraine. Methods: In this double-blind, placebo-controlled study, which was conducted over 6 months, randomized adult patients received subcutaneous injections of galcanezumab (120 mg n = 115, 240 mg n = 114) or placebo ( n = 230) once monthly. The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days. The key secondary outcome measures were response rates (≥50%, ≥75%, and 100%); the Migraine-Specific Quality-of-Life Questionnaire Role Function-Restrictive score; monthly migraine headache days requiring acute treatment; and Patient Global Impression of Severity (PGI-S). Results: The mean change from baseline in monthly migraine headache days over months 1–6 was significantly ( p < 0.001) greater for the 120-mg galcanezumab dose (−3.60 days) and the 240-mg galcanezumab dose (−3.36 days) compared with placebo (−0.59 days). Both the 120-mg and 240-mg doses of galcanezumab were superior compared with placebo for each of the key secondary endpoints except for PGI-S (only the 240-mg dose was superior). The most commonly reported treatment-emergent adverse events were local injection-site reactions; erythema, swelling, pruritus, and pain were more commonly reported by patients who were treated with galcanezumab than those treated with placebo. Conclusion: The number of monthly migraine headache days was reduced with both doses of galcanezumab, and both doses were safe and well tolerated in Japanese patients with episodic migraine.

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Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.4.1574 ◽

1998 ◽

Vol 16 (4) ◽

pp. 1574-1581 ◽

Cited By ~ 298

Author(s):

A N Serafini ◽

S J Houston ◽

I Resche ◽

D P Quick ◽

F M Grund ◽

...

Keyword(s):

Pain Relief ◽

Bone Metastases ◽

Active Drug ◽

Opioid Analgesic ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Complete Relief ◽

Double Blind ◽

Double Blind Placebo ◽

To Receive

PURPOSE To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

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Efficacy of Phenazone in the Treatment of Acute Migraine Attacks: A Double-Blind, Placebo-Controlled, Randomized Study

Cephalalgia ◽

10.1111/j.1468-2982.2004.00764.x ◽

2004 ◽

Vol 24 (10) ◽

pp. 888-893 ◽

Cited By ~ 15

Author(s):

H Göbel ◽

A Heinze ◽

U Niederberger ◽

T Witt ◽

V Zumbroich

Keyword(s):

Adverse Events ◽

Randomized Study ◽

Controlled Study ◽

Acute Migraine ◽

Serious Adverse Events ◽

Double Blind ◽

Double Blind Placebo ◽

Number Of Patients ◽

Significant Difference ◽

Main Target

In this study we compared the efficacy of 1000 mg phenazone with that of placebo in the treatment of acute migraine attacks in a randomized double-blind, placebo-controlled study of 208 patients. The main target criterion was the number of patients with a pain reduction from severe or moderate to slight or no pain 2 h after taking the pain medication. The percentage of patients satisfying the main target criterion was 48.6% for phenazone and 27.2% ( P < 0.05) for placebo. Freedom from pain after 2 h was reported by 27.6% with phenazone treatment and 13.6% ( P < 0.05) with placebo. Compared with placebo, the phenazone treatment also resulted in a significant improvement in the associated migraine symptoms of nausea, phonophobia and photophobia. Of patients treated with phenazone 11.4%, and 5.8% of those treated with placebo reported adverse events. There was no significant difference between the groups with regard to numbers of patients with adverse events. No serious adverse events occurred. The results show that phenazone at a dosage of 1000 mg is effective and well tolerated in the treatment of acute migraine attacks.

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Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-209213 ◽

2016 ◽

Vol 76 (5) ◽

pp. 811-820 ◽

Cited By ~ 77

Author(s):

Thomas Bardin ◽

Robert T Keenan ◽

Puja P Khanna ◽

Jeff Kopicko ◽

Maple Fung ◽

...

Keyword(s):

Adverse Events ◽

Laboratory Data ◽

Standard Of Care ◽

Phase Iii ◽

Controlled Study ◽

Inadequate Response ◽

Double Blind ◽

Significant Treatment ◽

End Points ◽

Registration Number

ObjectivesDetermine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial.MethodsPatients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data.ResultsPatients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively.ConclusionLesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy.Trial registration numberNCT01493531.

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Variability in the Reporting Terminology of Adverse Events and Complications in Ankle Fracture Fixation: A Systematic Review

Foot & Ankle International ◽

10.1177/1071100719879930 ◽

2019 ◽

Vol 41 (2) ◽

pp. 170-176

Author(s):

Stefan A. St George ◽

Hooman Sadr ◽

Chayanin Angthong ◽

Murray Penner ◽

Peter Salat ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Fracture Fixation ◽

Ankle Fracture ◽

Soft Tissue Injuries ◽

Classification Systems ◽

Level Of Evidence ◽

Implant Complications ◽

Frequency Of Use ◽

Standardized Reporting

Background: Classification systems for the reporting of surgical complications have been developed and adapted for many surgical subspecialties. The purpose of this systematic review was to examine the variability and frequency of reporting terms used to describe adverse events and complications in ankle fracture fixation. We hypothesized that the terminology used would be highly variable and inconsistent, corroborating previous results that have suggested a need for standardized reporting terminology in orthopedics. Methods: Ankle fracture outcome studies meeting predetermined inclusion and exclusion criteria were selected for analysis by 2 independent observers. Terms used to define adverse events and complications were identified and recorded. Discrepancies were resolved by consensus with the aid of a third observer. All terms were then compiled and assessed for variability and frequency of use throughout the studies involved. Reporting terminology was subsequently grouped into 10 categories. Results: In the 48 studies analyzed, 301 distinct terms were utilized to describe complications or adverse events. Of these terms, 74.4% (224/301) were found in a single study each. Only 1 term, “infection,” was present in 50% of studies, and only 19 of 301 terms (6.3%) were used in at least 10% of papers. The category that was most frequently reported was “infection,” with 89.6% of studies reporting on this type of adverse event using 25 distinct terms. Other categories were “wound healing complications” (72.9% of papers, 38 terms), “bone/joint complications” (66.7% of papers, 35 terms), “hardware/implant complications” (56.3% of papers, 47 terms), “revision” (56.3% of papers, 35 terms), “cartilage/soft tissue injuries” (45.8% of papers, 31 terms), “reduction/alignment issues” (45.8% of papers, 29 terms), “medical complications” (43.8% of papers, 32 terms), “pain” (29.2% of papers, 16 terms), and “other complications” (20.8% of papers, 13 terms). There was a 78.6% interobserver agreement in the identification of terms across the 48 studies included. Conclusion: The reporting terminology utilized to describe complications and adverse events in ankle fracture fixation was found to be highly variable and inconsistent. This variability prevents accurate reporting of complications and adverse events and makes the analysis of potential outcomes difficult. The development of standardized reporting terminology in orthopedics would be instrumental in addressing these challenges and allow for more accurate and consistent outcome reporting. Level of Evidence: Level III; systematic review of Level III studies and above.

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167 Randomized, Double-Blind, Active-Controlled Study of Starting Aripiprazole Lauroxil with 1-Day Initiation in Acutely Ill Patients with Schizophrenia

CNS Spectrums ◽

10.1017/s1092852920000838 ◽

2020 ◽

Vol 25 (2) ◽

pp. 306-307

Author(s):

Peter J. Weiden ◽

Amy Claxton ◽

Yangchun Du ◽

Sergey Yagoda ◽

David Walling ◽

...

Keyword(s):

Adverse Events ◽

Outpatient Setting ◽

Controlled Study ◽

Injection Site Pain ◽

Efficacy And Safety ◽

Double Blind ◽

Secondary Analyses ◽

Site Pain ◽

Over Time ◽

Funding Acknowledgements

Abstract:Objective:Evaluate efficacy and safety of a 2-month dose of aripiprazole lauroxil (AL) with a 1-day initiation regimen during hospitalization for an acute exacerbation of schizophrenia.Methods:In the phase 3b double-blind ALPINE study, adults with schizophrenia were randomized to AL (AL NanoCrystal® Dispersion + oral aripiprazole 30 mg day 1; AL 1064 mg day 8 and every 8 weeks) or paliperidone palmitate (PP 234 mg day 1; PP 156 mg day 8 and every 4 weeks). Patients were discharged after 2 weeks of hospitalization and followed through week 25. Primary endpoint was within-group changes in PANSS total score from baseline to week 4 (observed cases). Secondary analyses included within-group changes at weeks 9 and 25 (observed) and between-group comparisons at weeks 4, 9, and 25 (MMRM). Adverse events (AEs) were monitored throughout the study.Results:200 patients were randomized (AL, n=99; PP, n=101); 56.6% and 42.6%, respectively, completed the study. Within-group changes from baseline in PANSS were −17.4 for AL and −20.1 for PP at week 4 (both groups, P<0.001) and continued to decline at weeks 9 (AL, −19.8; PP, −22.5) and 25 (AL, −23.3; PP, −21.7). The change in PANSS over time was similar between groups. AEs occurring in ≥10% of patients in either group were injection site pain (AL, 17.2%; PP, 24.8%), akathisia (AL, 9.1%; PP, 10.9%), and weight increased (AL, 9.1%; PP, 16.8%).Conclusions:AL and PP were effective and well-tolerated for initiating treatment of schizophrenia in the hospital and continuing in the outpatient setting.Funding Acknowledgements:This study was funded by Alkermes, Inc.

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