Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase

LBA6008 Background: Lenvatinib (LEN) is an oral tyrosine kinase inhibitor of the VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT signaling networks. Based on efficacy results of the phase 2 study of patients (pts) with 131I-refractory differentiated thyroid cancer (RR-DTC), this phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) was developed. Methods: This randomized, double-blind, placebo (PBO)-controlled study enrolled pts with RR-DTC with documented disease progression within 13 months (mo). Pts were stratified by age (≤65, >65 years), region and ≤1 prior VEGFR-targeted therapies and randomized 2:1 to LEN or PBO (24mg/d, 28-d cycle). Upon progression, pts receiving PBO could crossover to open-label LEN. The primary endpoint was PFS assessed by Independent Radiologic Review; secondary endpoints included overall response rate (ORR; complete response [CR] + PR), overall survival (OS) and safety. Results: 392 pts (63.0 years median age; 51.0% male) were randomized. Pts on LEN had a significantly prolonged PFS vs PBO (hazard ratio 0.21, 95% confidence interval [CI] 0.14–0.31; P <.0001); median PFS was LEN: 18.3 mo (95% CI 15.1–not evaluable), PBO: 3.6 mo (95% CI 2.2–3.7). A LEN PFS benefit was observed in all predefined subgroups; median LEN PFS for pts with prior vs no prior VEGF-therapy was 15.1 mo (n=66) and 18.7 mo (n=195), respectively. Rates (n) of CRs were LEN: 1.5% (4), PBO: 0; PRs were LEN: 63.2% (165), PBO: 1.5% (2).Median exposure duration was LEN: 13.8 mo, PBO: 3.9 mo; median time to LEN response was 2.0 mo. Median OS has not been reached; deaths per arm were LEN: 71 (27.2%), PBO: 47 (35.9%). The 5 most common LEN treatment-related adverse events (TRAEs; any grade) were hypertension (68%), diarrhea (59%), appetite decreased (50%), weight loss (46%), nausea (41%). LEN grade ≥3 TRAEs (≥5%) were hypertension (42%), proteinuria (10%), weight loss (10%), diarrhea (8%), appetite decreased (5%). The dose was reduced in 78.5% of pts and discontinued due to adverse events (AEs) in 14.2% of pts. Conclusions: LEN significantly improved PFS compared with PBO in pts with progressive RR-DTC. There were no unexpected toxicities and AEs were manageable. Clinical trial information: NCT01321554.

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Addition of an oral histamine antagonist to reduce adverse events associated with fumaric acid esters in the treatment of psoriasis: a randomized double-blind placebo-controlled trial

British Journal of Dermatology ◽

10.1111/bjd.13277 ◽

2015 ◽

Vol 172 (3) ◽

pp. 754-759 ◽

Cited By ~ 7

Author(s):

D.M.W. Balak ◽

S. Fallah-Arani ◽

C.M. Venema ◽

H.A.M. Neumann ◽

H.B. Thio

Keyword(s):

Adverse Events ◽

Fumaric Acid ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo ◽

Fumaric Acid Esters ◽

Acid Esters ◽

Histamine Antagonist

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Safety and efficacy of glycopyrrolate as a premedication for endoscopic submucosal dissection: a randomized, double-blind, placebo-controlled study

Endoscopy ◽

10.1055/s-0043-112491 ◽

2017 ◽

Vol 49 (10) ◽

pp. 949-956 ◽

Cited By ~ 1

Author(s):

Eui Kim ◽

Min Um ◽

Kyoung Kim ◽

Jung Kim ◽

Su Kim ◽

...

Keyword(s):

Adverse Events ◽

Endoscopic Submucosal Dissection ◽

Medical Center ◽

Controlled Trial ◽

Controlled Study ◽

Research Information ◽

Serious Adverse Events ◽

Double Blind ◽

Double Blind Placebo ◽

Submucosal Dissection

Abstract Background and study aims Anticholinergic premedication has not been validated for endoscopic submucosal dissection (ESD). In this randomized, double-blind, placebo-controlled trial, we investigated the efficacy and safety of glycopyrrolate as a premedication for ESD. Methods A total of 196 patients undergoing ESD at a single tertiary medical center between December 2014 and February 2016 were randomly allocated to receive one of the following two premedications: glycopyrrolate (0.004 mg/kg intramuscularly [IM]) or placebo (2.0 mL normal saline solution IM). All patients received the premedication 30 minutes prior to ESD in a double-blind manner. The endoscopists reported the ease of performing the procedure and the incidence of secretion-induced hypoxemia, cough, and other procedure-related adverse events. Results Glycopyrrolate and placebo were received by 96 and 100 patients, respectively. ESD was successfully performed in all patients without any serious adverse events related to sedation or ESD. The median visual analog scale for procedure ease was higher in the glycopyrrolate group at 8 (interquartile range [IQR] 7 – 9) vs. 7 (IQR 6 – 8.25); P < 0.001. The proportions of patients with secretion-induced hypoxemia (4.4 % vs. 14.3 %; P = 0.03) and cough (16.7 % vs. 35.7 %; P = 0.005) were lower in the glycopyrrolate group. Conclusions The use of glycopyrrolate as a premedication for ESD significantly improved the ease of performing the procedure and reduced the incidence of secretion-induced hypoxemia and cough during ESD. Glycopyrrolate may be a promising premedication to ensure safe and stable ESD procedures.Trial registration: Clinical Research Information Service (CRIS): KCT0001540.

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Effects of a continuous low-dose clonidine epidural regimen on pain, satisfaction and adverse events during labour: a randomized, double-blind, placebo-controlled trial

European Journal of Anaesthesiology ◽

10.1097/eja.0b013e3283365944 ◽

2010 ◽

Vol 27 (5) ◽

pp. 441-447 ◽

Cited By ~ 18

Author(s):

Florent Wallet ◽

Henri Jacques Clement ◽

Carine Bouret ◽

Felix Lopez ◽

Françoise Broisin ◽

...

Keyword(s):

Adverse Events ◽

Low Dose ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo

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The Lipid lowering and Onset of Renal Disease (LORD) Trial: A randomized double blind placebo controlled trial assessing the effect of atorvastatin on the progression of kidney disease

BMC Nephrology ◽

10.1186/1471-2369-9-4 ◽

2008 ◽

Vol 9 (1) ◽

Cited By ~ 24

Author(s):

Robert G Fassett ◽

Madeleine J Ball ◽

Iain K Robertson ◽

Dominic P Geraghty ◽

Jeff S Coombes

Keyword(s):

Kidney Disease ◽

Renal Disease ◽

Controlled Trial ◽

Lipid Lowering ◽

Double Blind ◽

Double Blind Placebo ◽

Progression Of Kidney Disease

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Methylphenidate for Mild Cognitive Impairment: An Exploratory 3-Day, Randomized, Double-Blind, Placebo-Controlled Trial

Frontiers in Medicine ◽

10.3389/fmed.2021.594228 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yan Press ◽

Boris Punchik ◽

Ella Kagan ◽

Alexander Berzak ◽

Tamar Freud ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Adverse Events ◽

Verbal Memory ◽

Cognitive Assessment ◽

Controlled Trial ◽

Immediate Release ◽

Cognitive Outcome ◽

Double Blind ◽

Double Blind Placebo

Background: To evaluate the efficacy, safety and tolerability of methylphenidate (MPH) for cognitive function in older patients with mild cognitive impairment (MCI).Methods: Male and female subjects aged 65 years and older with a clinical diagnosis MCI were included in an exploratory randomized, double-blind, placebo-controlled trial. Eligible subjects were assigned to either treatment with immediate-release MPH or placebo. The active compound was administered in an increasing-dose stepwise fashion, namely 10 mg MPH on day 1, 20 mg on day 2, and 30 mg on day 3. Subjects remained under observation for 4 h following drug administration and were monitored for changes in blood pressure and for adverse events. Cognitive outcome measures included the Montreal Cognitive Assessment (MoCA) and the Neurotrax Mindstreams computerized cognitive assessment battery.Results: Of 17 subjects enrolled, 15 subjects completed the study, 7 in the active MPH group and 8 in the placebo group. The average age of the participants was 76.1 ± 6.6 years and 10 (66.7%) were men. Following the final dose a significant benefit on memory (predominantly non-verbal memory) was found in the MPH group. While 12 adverse events were reported, they were all rated as mild to moderate.Conclusions: Our finding of modest beneficial effects of MPH on memory tests in older subjects with MCI in this exploratory study is of interest and should be investigated in further studies.

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Treatment of acute bronchitis in adults with extract of Pelargonium Sidoides: a randomised, double-blind, placebo controlled trial

Russian Pulmonology ◽

10.18093/0869-0189-2007-0-6-49-55 ◽

2007 ◽

pp. 49-55

Author(s):

A. G. Chuchalin ◽

B. Berman ◽

V. Lemakher

Keyword(s):

Placebo Group ◽

Adverse Events ◽

Controlled Trial ◽

Alternative Therapy ◽

Acute Bronchitis ◽

Complete Recovery ◽

Primary Outcome Measure ◽

Double Blind ◽

Double Blind Placebo ◽

Pelargonium Sidoides

Acute bronchitis is a wide-spread disease. Although it is generally caused by viruses, antibiotics are used for its treatment too much often. So it is very important to evaluate alternative therapy of acute bronchitis. The aim of the trial was to assess efficacy and safety of Pelargonium Sidoides (EPs 7630 is a registered trademark of Dr. Willmar Schwabe GmbH & Co, Karlsruhe, Germany) compared to placebo in patients with acute bronchitis. Study design: randomised, double-blind, placebo controlled trial with planned interim analysis. The trial centres: 6 outpatient medical centres. Patients: 124 adult patients with acute bronchitis, onset of the disease ≤ 48 h, and severity of symptoms ≥ 5 according to BSS scale gave written informed concert. EPs 7630 or placebo were administered in the dose of 30 drops t.i.d. during 7 days. The primary outcome measure was BSS scoring at the 7th day of the treatment. BSS scoring decreased by 7.2 ± 3.1 in the EPs 7630 group (n = 64) vs 4.9 ± 2.7 in the placebo group (n = 60). 95 % confidence interval (CI, 1.21, 3.56) for difference of the effects between two groups demonstrated significant improvement in the EPs 7630 in 7 days of the treatment compared to the placebo group (p < 0.0001). The EPs 7630 patients had parameters of complete recovery for every of 5 individual symptoms reliably higher compared to placebo patients. During the first 4 days of the treatment therapeutic effect was noted in 68.8 % of the EPs 7630 group vs 33.3 % of the placebo group (p < 0.0001). Health-related quality of life improved better in the EPs 7630 patients compared to the placebo group. Adverse events were found in 25 of 124 patients: 15 / 64 in the EPs 7630 group and 10 / 60 in the placebo group. All the adverse events were considered as non-serious. The efficacy of EPs 7630 in treatment of adults with acute bronchitis was higher compared to placebo. It could be an efficient alternative drug in therapy of acute bronchitis at the absence of indications for antibiotics administration.

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