Double-dummy là gì

Double-blind, randomized, double-dummy clinical trial comparing the efficacy of ketorolac trometamol and naproxen for acute low back pain

PubMed Central

Plapler, Pérola Grinberg; Scheinberg, Morton Aaron; Ecclissato, Christina da Cunha; Bocchi de Oliveira, Monalisa Fernanda; Amazonas, Roberto Bleuel

2016-01-01

Background Nonsteroidal anti-inflammatory drugs [NSAIDs] are the most common type of medication used in the treatment of acute pain. Ketorolac trometamol [KT] is a nonnarcotic, peripherally acting nonsteroidal anti-inflammatory drug with analgesic effects comparable to certain opioids. Objective The aim of this study was to compare the efficacy of KT and naproxen [NA] in the treatment of acute low back pain [LBP] of moderate-to-severe intensity. Patients and methods In this 10-day, Phase III, randomized, double-blind, double-dummy, noninferiority trial, participants with acute LBP of moderate-to-severe intensity as determined through a visual analog scale [VAS] were randomly assigned in a 1:1 ratio to receive sublingual KT 10 mg three times daily or oral NA 250 mg three times daily. From the second to the fifth day of treatment, if patient had VAS >40 mm, increased dosage to four times per day was allowed. The primary end point was the reduction in LBP as measured by VAS. We also performed a post hoc superiority analysis. Results KT was not inferior to NA for the reduction in LBP over 5 days of use as measured by VAS scores [P=0.608 for equality of variance; P=0.321 for equality of means] and by the Roland–Morris Disability Questionnaire [P=0.180 for equality of variance test; P=0.446 for equality of means] using 95% confidence intervals. The percentage of participants with improved pain relief 60 minutes after receiving the first dose was higher in the KT group [24.2%] than in the NA group [6.5%; P=0.049]. The most common adverse effects were heartburn, nausea, and vomiting. Conclusion KT is not inferior in efficacy and delivers faster pain relief than NA. PMID:27382251

Chinese herbal medicine [Ma Zi Ren Wan] for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial

PubMed Central

2013-01-01

Background Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. Methods/Design This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients [Rome III] with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm [Ma Zi Ren Wan and western medicine placebo], western medicine arm [senna and Chinese medicine placebo] or placebo arm [Chinese medicine placebo and western medicine placebo]. Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement [CSBM] during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. Discussion This study is the first study to compare a Chinese Herbal Medicine [Ma Zi Ren Wan] with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other

Chinese herbal medicine [Ma Zi Ren Wan] for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial.

PubMed

Zhong, Linda L D; Cheng, Chung Wah; Chan, Yawen; Chan, King Hong; Lam, Ting Wa; Chen, Xiao Rui; Wong, Chi Tak; Wu, Justin C Y; Bian, Zhao Xiang

2013-11-04

Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients [Rome III] with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm [Ma Zi Ren Wan and western medicine placebo], western medicine arm [senna and Chinese medicine placebo] or placebo arm [Chinese medicine placebo and western medicine placebo]. Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement [CSBM] during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. This study is the first study to compare a Chinese Herbal Medicine [Ma Zi Ren Wan] with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine

Chuanhu Anti-Gout Mixture versus Colchicine for Acute Gouty Arthritis: A Randomized, Double-Blind, Double-Dummy, Non-Inferiority Trial

PubMed Central

Wang, YanGang; Wang, Luan; Li, EnZe; Li, Yang; Wang, ZhongChao; Sun, XiaoFang; Yu, XiaoLong; Ma, Lin; Wang, YunLong; Wang, YouXin

2014-01-01

Background The Chuanhu anti-gout mixture has been used for many years in the treatment of gout in Chinese Traditional Medicine, and current methods for treatments for acute gouty arthritis have been either less effective or have had serious side effects. Methods In this 12-week, double-blind, double-dummy, non-inferiority study, outpatient individuals with newly diagnosed acute gouty arthritis were randomly assigned to receive Chuanhu anti-gout mixture or colchicine. Both the study investigators and the participants were masked to the treatment assignments. The primary outcome was the recurrence rate of acute gouty arthritis, and the secondary outcomes were changes in white blood cells [WHC] and C-reactive protein [CRP]. This trial is registered at ISRCTN.org as trial ISRCTN65219941. Results A total of 176 patients were randomly assigned to receive either the Chuanhu anti-gout mixture or Colchicine. The overall recurrence rates in the Chuanhu anti-gout mixture group [CH group] and the Colchicine group [Col group] were 12.50% vs 14.77% [difference -2.22%, 95% confidence interval [95% CI]: -10.78%~6.23%], meeting the predefined non-inferiority criterion of 15%, as did the data for WHC and CRP. The incidence of adverse events [mainly diarrhea] was less in the Col group than in the CH group [2.27% vs 28.41%, 95% CI 0.01~0.26]. In addition, changes in blood uric acid, alanine aminotransferase, aspartate aminotransferase and creatinine in the CH group were significantly larger compared to those in the Col group [P53 and ≤91 mmol/mol] [N = 482] were randomized to 24 weeks' double-blind, double-dummy treatment with linagliptin 5 mg or placebo in study 1, or to linagliptin 5 mg or placebo in study 2; all patients continued treatment with metformin and empagliflozin 10 mg [study 1] or metformin and empagliflozin 25 mg [study 2]. The primary endpoint was change from baseline [defined as the last value before first intake of randomized, double-blind treatment] in HbA1c at week 24. At week 24, HbA1c [mean baseline 7.82-8.04 [62-64 mmol/mol]] was significantly reduced with linagliptin vs placebo; adjusted mean [SE] differences in change from baseline in HbA1c with linagliptin vs placebo were -.32% [.10] [-3.59 [1.08] mmol/mol] [ P = .001] for patients on empagliflozin 10 mg and metformin, and -0.47% [0.10] [-5.15 [1.04] mmol/mol] [ P < 0.001] for patients on empagliflozin 25 mg and metformin. Adverse events were reported in more patients receiving placebo than in those receiving linagliptin: 55.5% vs 48.4% in study 1 and 58.9% vs 52.7% in study 2. Linagliptin as add-on to empagliflozin and metformin for 24 weeks improved glycaemic control vs placebo, and was well tolerated. © 2016 John Wiley & Sons Ltd.

Efficacy and safety of acarbose chewable tablet in patients with type 2 diabetes: a multicentre, randomized, double-blinded, double-dummy positive controlled trial.

PubMed

Wu, Qian Lin; Liu, Yu Ping; Lu, Ju Ming; Wang, Chang Jiang; Yang, Tao; Dong, Ji Xiang; Li, Cheng Jiang; Ma, Jian Hua; Xue, Yao Ming; Sun, Rui Hua; Wei, Dong; Tian, Hao Ming

2012-08-01

To evaluate the effect and safety of HbA1c and glycemic control of acarbose chewable tablets in patients with type 2 diabetic. A multicentre, randomized, double-blinded, double-dummy, positive controlled clinical trial was conducted. Two hundred thirty-four Chinese patients with type 2 diabetic were enrolled in eight clinical centres, who were divided randomly into the acarbose chewable tablet group [experimental group, n = 116] and the acarbose treatment group [control group, n = 118]. Two hundred seven patients [88.5%] took part in the 12-week trial. At the beginning and end of the clinical trial, HbA1c and blood glucose as well as safety indexes were measured. After the treatment, the level of finger two-hour postprandial blood glucose [PPBG] was decreased 4.15 mmol/L [26.82%] and 3.54 mmol/L [22.77%], respectively, in the experiment group and the control group. The levels of venous two-hour PPBG in the experiment group and the control group were decreased 4.04 mmol/L [25.38%] and 2.75 mmol/L [17.26%], respectively, with the means of HbA1c lowering 11.67% and 12.44%, respectively. Fasting blood glucose [FBG] also was reduced significantly in both groups. Patients in both groups showed obvious weight reduction [P < 0.0001]. There were no significant differences in the incidence of adverse events between the two groups. In summary, acarbose chewable tablets have a definite curative effect in treating type 2 diabetic patients as HbA1c and blood glucose levels decreased significantly after the 12-week treatment. © 2012 Wiley Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Interaction of clopidogrel and statins in secondary prevention after cerebral ischaemia – a randomized, double-blind, double-dummy crossover study

PubMed Central

Siepmann, Timo; Heinke, Denise; Kepplinger, Jessica; Barlinn, Kristian; Gehrisch, Siegmund; Grählert, Xina; Schwanebeck, Uta; Reichmann, Heinz; Puetz, Volker; Bodechtel, Ulf; Gahn, Georg

2014-01-01

Aims Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 [CYP] 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to CYP 2C9-metabolized fluvastatin, reduces clopidogrel-mediated platelet inhibition. Methods We performed a randomized, double-blind, double-dummy, two period crossover study in 13 patients with cerebral ischaemia [8F, 5 M], aged 64.1 ± 8.0 years [mean ± SD]. After a 14 day period in which all patients received 75 mg clopidogrel day−1, patients additionally received either 20 mg simvastatin day−1 or 80 mg fluvastatin day−1 for 14 days. Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite [CAM] plasma concentrations and routine laboratory parameters including prothrombin time [PT] Quick percent value were assessed at baseline and following each treatment phase. Results Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value [decrease from 109 ± 10.5% to 103 ± 11%, P < 0.05] when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel. Conclusions Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation. After co-administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1 + 2. PMID:24803100

Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind, Double Dummy, Randomized Study.

PubMed

Furtado, Remo Holanda de Mendonça; Giugliano, Robert Patrick; Strunz, Celia Maria Cassaro; Filho, Cyrillo Cavalheiro; Ramires, José Antonio Franchini; Filho, Roberto Kalil; Neto, Pedro Alves Lemos; Pereira, Alexandre Costa; Rocha, Tânia Rúbia; Freire, Beatriz Tonon; D'Amico, Elbio Antonio; Nicolau, José Carlos

2016-08-01

Proton-pump inhibitors [PPIs] are often prescribed to patients receiving dual antiplatelet therapy [DAPT]. However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine. Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine. We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily [bid] or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12™ [Accumetrics; San Diego, CA, USA], depicting aggregability as percent inhibition of platelet aggregation [IPA]. We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel [from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025], with no statistical significant changes observed in the ranitidine group [from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310]. The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance [p = 0.07, 95 % confidence interval [CI] -1.19 to 26.59]; after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance [32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04]. Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel. NCT01896557.

A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone

PubMed Central

Kopecky, Ernest A.; Smith, Michael D.; Fleming, Alison B.

2016-01-01

Objective. Evaluate the human abuse potential [HAP] of an experimental, microsphere-in-capsule formulation of extended-release oxycodone [oxycodone DETERx®] [herein “DETERx”]. Design. Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. Setting. Clinical research site. Subjects. There were 39 qualifying subjects [72% male, 85% white, mean age of 27 years] with 36 completing all four Double-blind Treatment Periods. Methods. The four phases encompassed: 1] Screening; 2] Drug Discrimination; 3] Double-blind Treatment; and 4] Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx—administered as either a crushed intranasal [IN] or an intact oral [PO] preparation—with immediate-release oxycodone IN [OXY-IR IN] and with an intact IN and PO placebo DETERx control. Results. For primary pharmacokinetic [PK] assessments, abuse quotient [Cmax/Tmax] was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN [6.24, 8.60, and 69.6 ng/mL/h, respectively]. For drug liking, the primary subjective pharmacodynamic [PD] endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN [P ≤ 0.0001 for each]; DETERx IN was less liked than DETERx PO [P ≤ 0.05], mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO [P ≤ 0.007 for each]. Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated. Conclusions. Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested. PMID:26814256

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

PubMed

Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

2016-06-01

A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction [SD-rATG] showed improved efficacy compared with conventional divided-dose [DD-rATG] administration. The present multicenter, double-blind/double-dummy STAT trial [Single dose vs. Traditional Administration of Thymoglobulin] evaluated SD-rATG versus DD-rATG induction for noninferiority in early [7-day] safety and tolerability. Ninety-five patients [randomized 1:1] received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction [p = 0.6], and a conditional probability of 50 years: a double-blind, double-dummy, randomized controlled trial.

PubMed

Sengupta, Gairik; Hazra, Avijit; Kundu, Anup; Ghosh, Anirban

2011-12-01

Drug treatment can defer surgical intervention in benign prostatic hyperplasia [BPH], a common disorder in elderly men, and is widely practiced. Various herbal formulations have been used for the treatment of BPH, but few have been compared with established modern medicines in head-to-head clinical trials. We compared the effectiveness and tolerability of an oral formulation, comprising standardized extracts of Murraya koenigii and Tribulus terrestris leaves being marketed in India under Ayurvedic license, versus tamsulosin in the treatment of symptomatic BPH. A double-blind, double-dummy, parallel-group, randomized controlled trial was conducted with treatment-naive ambulatory patients with BPH aged >50 years. Patients received either the plant drug in a dose of 2 capsules BID or tamsulosin 400 μg once daily for 12 weeks with 2 interim follow-up visits at the end of 4 and 8 weeks. The double-dummy technique was used to ensure double-blinding. The primary effectiveness measure was reduction in the International Prostate Symptom Score [IPSS]. Proportion of patients becoming completely or relatively symptom free [IPSS 0.05]. At week 12, no significant difference was shown between the two groups in BG or haemoglobin A[1c] [HbA[1c]] [p > 0.05]. However, the effect on HbA[1c] in repaglinide group was stronger than that in nateglinide group [p < 0.05]. After 12-week treatment, area under the curve [AUC] of BG decreased [p < 0.05], and AUC of insulin and C-peptide [CP] increased in both groups [p < 0.05]. The effects of nateglinide on AUC of BG, insulin and CP were similar to that of repaglinide [p > 0.05]. There was no significant difference between the two groups in AUC of BG, insulin or CP in week 12 [p > 0.05]. Furthermore, homeostasis model assessment of insulin resistance [HOMA-IR] and beta-cell function indexes measured by HOMA-beta, DeltaI[30]/DeltaG[30] and [DeltaI[30]/DeltaG[30]]/HOMA-IR were improved significantly in both groups during 12 weeks [p < 0.05]. The effects of improving HOMA-IR and beta-cell function indexes in nateglinide group were comparable with that of repaglinide group [p > 0.05]. The efficacy of repaglinide and nateglinide in FBG, postprandial glucose excursion and early-phase insulin secretion is similar. But the

Bupropion and Naltrexone for Smoking Cessation: A Double-Blind Randomized Placebo-Controlled Clinical Trial

PubMed Central

Mooney, Marc E.; Schmitz, Joy M.; Allen, Sharon; Grabowski, John; Pentel, Paul; Oliver, Andrew; Hatsukami, Dorothy K.

2016-01-01

Combination of non-nicotine pharmacotherapies has been under-examined for cigarette smoking cessation. A randomized, double-blind, parallel-group double-dummy study evaluated two medications, bupropion [BUP] and naltrexone [NTX], in treatment-seeking cigarette smokers [N = 121] over a 7-week treatment intervention with 6-month follow-up. Smokers were randomized to either BUP [300 mg/day] + Placebo [PBO] or BUP [300 mg/day] + NTX [50 mg/day]. The primary outcome was biochemically-verified [saliva cotinine, carbon monoxide] 7-day, point-prevalence abstinence. BUP+NTX was associated with significantly higher point-prevalence abstinence rates after 7-weeks of treatment [BUP+NTX, 54.1%; BUP+PBO, 33.3%], p = 0.0210, but not at 6-month follow-up [BUP+NTX, 27.9%; BUP+PBO, 15.0%], p = 0.09. Continuous abstinence rates did not differ, p = 0.0740 [BUP+NTX, 26.2%; BUP+PBO, 13.3%]. Those receiving BUP+NTX reported reduced nicotine withdrawal, p = 0.0364. The BUP+NTX combination was associated with elevated rates of some side effects, but with no significant difference in retention between the groups. PMID:27213949