Effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery: multicentre, double blind, randomised controlled trial

Abstract Objective To assess the effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery. Design Phase III, randomised, double blind, placebo controlled trial. Setting 34 centres in France, December 2017 to March 2019. Participants 1222 adults (>50 years) requiring major non-cardiac surgery with an expected duration of more than 90 minutes. The anticipated time frame for recruitment was 24 months. Interventions Participants were randomised to receive either dexamethasone (0.2 mg/kg immediately after the surgical procedure, and on day 1) or placebo. Randomisation was stratified on the two prespecified criteria of cancer and thoracic procedure. Main outcomes measures The primary outcome was a composite of postoperative complications or all cause mortality within 14 days after surgery, assessed in the modified intention-to-treat population (at least one treatment administered). Results Of the 1222 participants who underwent randomisation, 1184 (96.9%) were included in the modified intention-to-treat population. 14 days after surgery, 101 of 595 participants (17.0%) in the dexamethasone group and 117 of 589 (19.9%) in the placebo group had complications or died (adjusted odds ratio 0.81, 95% confidence interval 0.60 to 1.08; P=0.15). In the stratum of participants who underwent non-thoracic surgery (n=1038), the primary outcome occurred in 69 of 520 participants (13.3%) in the dexamethasone group and 93 of 518 (18%) in the placebo group (adjusted odds ratio 0.70, 0.50 to 0.99). Adverse events were reported in 288 of 613 participants (47.0%) in the dexamethasone group and 296 of 609 (48.6%) in the placebo group (P=0.46). Conclusions Dexamethasone was not found to significantly reduce the incidence of complications and death in patients 14 days after major non-cardiac surgery. The 95% confidence interval for the main result was, however, wide and suggests the possibility of important clinical effectiveness. Trial registration ClinicalTrials.gov NCT03218553 .

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Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo-controlled trial

Stroke and Vascular Neurology ◽

10.1136/svn-2021-000942 ◽

2021 ◽

pp. svn-2021-000942

Author(s):

Jingyi Liu ◽

Ximing Nie ◽

Hongqiu Gu ◽

Qi Zhou ◽

Haixin Sun ◽

...

Keyword(s):

Placebo Group ◽

Tranexamic Acid ◽

Intracerebral Haemorrhage ◽

Intracranial Haemorrhage ◽

Primary Outcome ◽

Controlled Trial ◽

Intracerebral Haematoma ◽

Spot Sign ◽

Double Blind ◽

Risk Of Death

BackgroundStudies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion.MethodsWe did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days.ResultsOf the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency.ConclusionsAmong patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.

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Continuous bilateral thoracic paravertebral blockade for analgesia after cardiac surgery: a randomised, controlled trial

Perfusion ◽

10.1177/0267659117715507 ◽

2017 ◽

Vol 32 (7) ◽

pp. 591-597 ◽

Cited By ~ 5

Author(s):

Geoff G. Lockwood ◽

Leilani Cabreros ◽

Dorota Banach ◽

Prakash P. Punjabi

Keyword(s):

Cardiac Surgery ◽

Primary Outcome ◽

Controlled Trial ◽

Morphine Consumption ◽

Controlled Study ◽

Double Blind ◽

Clinical Trial Registration ◽

Subcutaneous Infusion ◽

Randomised Controlled Study ◽

Randomised Controlled

Background: Continuous bilateral thoracic paravertebral blockade has been used for analgesia after cardiac surgery, but its efficacy has never been formally tested. Method: Fifty adult patients were enrolled in a double-blind, randomised, controlled study of continuous bilateral thoracic paravertebral infusion of 0.5% lidocaine (1 mg.kg-1.hr-1) for analgesia after coronary surgery. Control patients received a subcutaneous infusion of lidocaine at the same rate through catheters inserted at the same locations as the study group. The primary outcome was morphine consumption at 48 hours using patient-controlled analgesia (PCA). Secondary outcomes included pain, respiratory function, nausea and vomiting. Serum lidocaine concentrations were measured on the first two post-operative days. Results: There was no difference in morphine consumption or in any other outcome measure between the groups. Serum lidocaine concentrations increased during the study, with a maximum of 5.9 mg.l-1. There were no adverse events as a consequence of the study. Conclusion: Bilateral paravertebral infusion of lidocaine confers no advantage over systemic lidocaine infusion after cardiac surgery. Clinical trial registration: ISRCTN13424423 ( https://www.isrctn.com )

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Biomarker prediction of efficacy to vandetanib plus gemcitabine in a phase II double blind multicenter randomized placebo-controlled trial in locally advanced or metastatic pancreatic carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4104 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4104-4104 ◽

Cited By ~ 1

Author(s):

John P. Neoptolemos ◽

Daniel Palmer ◽

William Greenhalf ◽

Paula Ghaneh ◽

Richard Jackson ◽

...

Keyword(s):

Phase Ii ◽

Logistic Regression Model ◽

Primary Outcome ◽

Controlled Trial ◽

Locally Advanced ◽

Prospective Evaluation ◽

Double Blind ◽

Once Daily ◽

Intention To Treat ◽

Clinical Trial Information

4104 Background: We investigated the potential of biomarkers to predict efficacy of vandetanib and gemcitabine in patients with locally advanced (N = 41) or metastatic (N = 101) pancreatic cancer in a phase II double-blind multicentre randomised placebo-controlled trial. Methods: All patients were 18y or above, (ECOG = 0-2), with at least 3 mths life expectancy had gemcitabine (1000mg/m2 30min iv wkly for 7 wks, followed by a 1wk break, then cycles of wkly treatment for 3wks with a 1-wk break) and randomly assigned to 300mg/d vandetanib or placebo once daily until disease progression. The primary outcome was overall survival (OS) by intention to treat. A panel of potential biomarkers was tested to predict best survival with vandetanib and gemcitabine. Results: 142 patients were randomised, median FU = 24·9 mths with 131 deaths. The median (95% CI) OS in the 70 gemcitabine-placebo patients was 8·95 (6·55-11·7) mths and 8·83 (7·11-11·6) mths in the 72 gemcitabine-vandetanib patients (HR = 1·21, 95% CI = 0·85, 1·73; log rank X21df = 1·1; P = 0·303). A CTCAE V.4.02 rash grade 2 or above occurred in 4 (6 %) of 70 placebo patients versus 14 (19%) of 72 vandetanib patients. The median OS for the 14 vandetanib patients and with rash was 11·92 (10·89 – NA) mths, 7·76 (4·34 – 11·5) mths for the 58 vandetanib patients and without rash and 8·95 (6·55 – 11·7) mths for the gemcitabine-placebo patients (log rank Χ2 2df = 7·23; P = 0·03). We identified two biomarkers that could select patients for response to vandetanib (JN101, JN102). The biomarker combination was present in 26 patients with median OS of 12.1 (10.9, 16.0) mths versus 8.15 (6.67, 11.7) mths for 23 patients with the same biomarker profile in the placebo group (HR = 0.53 [0.29, 0.97], p = 0.0396). A logistic regression model showed that patients with JN102 were more likely to develop a rash (OR =0.81 [0.713, 0.925] p = 0.002). Conclusions: A two biomarker combination and a rash grade 2 or above may predict response to vandetanib and gemcitabine. This requires prospective evaluation. Clinical trial information: 96397434.

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Efficacy and Safety of Yokukansan in Treatment-Resistant Schizophrenia: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/201592 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Tsuyoshi Miyaoka ◽

Motohide Furuya ◽

Jun Horiguchi ◽

Rei Wake ◽

Sadayuki Hashioka ◽

...

Keyword(s):

Placebo Group ◽

Controlled Trial ◽

Controlled Study ◽

Efficacy And Safety ◽

Treatment Resistant ◽

Double Blind ◽

Double Blind Placebo ◽

Intention To Treat ◽

The Difference ◽

The Individual

Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan) in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted.Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).Results. TJ-54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS) and intention-to-treat (ITT). However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54:−0.23±0.08; placebo:−0.03±0.08,P<0.018), tension (TJ-54:−0.42±0.09; placebo:−0.18±0.09,P<0.045), and poor impulse control (TJ-54:−0.39±0.10; placebo:−0.07±0.10,P<0.037).Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores.

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Placebo-controlled trial of moclobemide in social phobia

The British Journal of Psychiatry ◽

10.1192/bjp.172.1.70 ◽

1998 ◽

Vol 172 (1) ◽

pp. 70-77 ◽

Cited By ~ 93

Author(s):

Franklin R. Schneier ◽

Deborah Goetz ◽

Raphael Campeas ◽

Randall Marshall ◽

Brian Fallon ◽

...

Keyword(s):

Social Phobia ◽

Outcome Measures ◽

Primary Outcome ◽

Controlled Trial ◽

Monoamine Oxidase A ◽

Reversible Inhibitor ◽

Double Blind ◽

Intention To Treat ◽

Independent Evaluator ◽

Single Blind

BackgroundMoclobemide, a reversible inhibitor of monoamine oxidase A, previously has been reported to have efficacy in the treatment of social phobia.MethodSeventy-seven non-responders to one week of single-blind placebo were randomly assigned to moclobemide or placebo for eight weeks of double-blind treatment. Outcome was assessed by independent evaluator, treating psychiatrist and self-ratings. After eight weeks, patients who were at least minimally improved continued treatment for a further eight weeks.ResultsIntention-to-treat sample response rates at week 8 were 7/40 (17.5%) for the moclobemide group and 5/37 (13.5%) for placebo (NS). Moclobemide was significantly superior to placebo on 2 of 10 primary outcome measures. Moclobemide was well tolerated.ConclusionsMoclobemide may have efficacy in the treatment of social phobia, but absence of significant differences on most primary outcome measures and small effect sizes for all outcome measures suggest that the magnitude of its clinical effect is small.

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Effects and Safety of Gyejibongnyeong-Hwan on Dysmenorrhea Caused by Blood Stagnation: A Randomized Controlled Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/424730 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

Jeong-Su Park ◽

Sunju Park ◽

Chun-Hoo Cheon ◽

Seong-Cheon Jo ◽

Han Baek Cho ◽

...

Keyword(s):

Placebo Group ◽

Controlled Trial ◽

Control Group ◽

Menstrual Pain ◽

Double Blind ◽

Menstrual Cycles ◽

Intention To Treat ◽

Investigational Drugs ◽

Significant Difference ◽

Vas Scores

Objective. This study was a multicenter, randomized, double-blind, and controlled trial with two parallel arms: the GJBNH group and the placebo group. This trial recruited 100 women aging 18 to 35 years with primary dysmenorrhea caused by blood stagnation. The investigational drugs, GJBNH or placebo, were administered for two menstrual periods (8 weeks) to the participants three times per day. The participants were followed up for two menstrual cycles after the administration.Results. The results were analyzed by the intention-to-treat (ITT) dataset and the per-protocol (PP) dataset. In the ITT dataset, the change of the average menstrual pain VAS score in the GJBNH group was statistically significantly lower than that in the control group. Significant difference was not observed in the SF-MPQ score change between the GJBNH group and the placebo group. No significant difference was observed in the PP analyses. In the follow-up phase, the VAS scores of the average menstrual pain and the maximum menstrual pain continually decreased in the placebo group, but they increased in the GJBNH group.Conclusion. GJBNH treatment for eight weeks improved the pain of the dysmenorrhea caused by blood stagnation, but it should be successively administered for more than two menstrual cycles.Trial Registration. This trial is registered with Current Controlled Trials no.ISRCTN30426947.

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Effect of Jeju Water on Blood Glucose Levels in Diabetic Patients: A Randomized Controlled Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/212918 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Gwanpyo Koh ◽

Dae Ho Lee ◽

Sang Ah Lee ◽

Eun-Kyung Kang ◽

Okkyeong Hwang ◽

...

Keyword(s):

Glycemic Control ◽

Primary Outcome ◽

Tap Water ◽

Controlled Trial ◽

Diabetic Patients ◽

Double Blind ◽

Glucose Levels ◽

Intention To Treat ◽

Blood Glucose Levels ◽

Patients With Diabetes

Jeju water is the groundwater of Jeju Island, a volcanic island located in Republic of Korea. We investigated whether Jeju water improved glycemic control in patients with diabetes. This was a 12-week single-center, double-blind, randomized, and controlled trial. The subjects daily drank a liter of one of three kinds of water: two Jeju waters (S1 and S2) and Seoul tap water (SS). The primary outcome was the proportion of patients in the per-protocol (PP) population achieving glycated hemoglobin (HbA1c)<7.0% at week 12. In total, 196 patients were randomized and analyzed in the intention-to-treat (ITT) population (66 consuming S1, 63 consuming S2, and 67 consuming SS); 146 patients were considered in the PP population. There were no significant differences in the primary outcomes of the groups consuming S1, S2, or SS. However, the percentage of patients achieving HbA1c<8% was significantly higher in the S2 group than in the SS group. In the ITT population, the 12-week HbA1c and fructosamine levels were lower in the S1 group than in the SS group and the 4-, 8-, and 12-week fructosamine levels were lower in the S2 group than in the SS group. Although we failed to achieve the primary outcome, it is possible that the Jeju waters improve glycemic control compared with the Seoul tap water in diabetic patients.

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A placebo-controlled double blind trial of hydroxychloroquine in mild-to-moderate COVID-19

10.1101/2020.10.19.20214940 ◽

2020 ◽

Cited By ~ 2

Author(s):

Vincent Dubée ◽

Pierre-Marie Roy ◽

Bruno Vielle ◽

Elsa Parot-Schinkel ◽

Odile Blanchet ◽

...

Keyword(s):

Primary Endpoint ◽

Controlled Trial ◽

Supplemental Oxygen ◽

Double Blind ◽

Intention To Treat ◽

Viral Shedding ◽

Virological Outcomes ◽

Secondary Endpoints ◽

To Receive ◽

Treat Population

AbstractBackgroundThe efficacy of hydroxychloroquine in coronavirus disease 2019 (COVID-19) remains controversial.MethodsWe conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: age ≥75 years, age between 60 and 74 years, and presence of at least one comorbidity, or need for supplemental oxygen (≤3 L/min). Eligible patients were randomized in a 1:1 ratio to receive either 800mg hydroxychloroquine on Day 0 followed by 400mg per day for 8 days or a placebo. The primary endpoint was a composite of death or tracheal intubation within 14 days following randomization. Secondary endpoints included mortality and clinical evolution at Day 14 and 28, viral shedding at Day 5 and 10.ResultsThe trial was stopped after 250 patients were included due to a slowdown of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years and 151 patients required oxygen therapy. The primary endpoint occurred in nine patients in the hydroxychloroquine group and eight patients in the placebo group (relative risk 1.12; 95% confidence interval 0.45– 2.80; P=0.82). No difference was observed between the two groups in any of the secondary endpoints.ConclusionIn this trial involving mainly older patients with mild-to-moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.

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Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery

Anesthesiology ◽

10.1097/aln.0000000000002751 ◽

2019 ◽

Vol 131 (1) ◽

pp. 119-131 ◽

Cited By ~ 9

Author(s):

Sibtain Anwar ◽

Jackie Cooper ◽

Junia Rahman ◽

Chhaya Sharma ◽

Richard Langford

Keyword(s):

Quality Of Life ◽

Cardiac Surgery ◽

Odds Ratio ◽

Rating Scale ◽

Controlled Trial ◽

Persistent Pain ◽

Control Group ◽

Analgesic Requirement ◽

Double Blind

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Persistent postsurgical pain is common and affects quality of life. The hypothesis was that use of pregabalin and ketamine would prevent persistent pain after cardiac surgery. Methods This randomized, double-blind, placebo-controlled trial was undertaken at two cardiac surgery centers in the United Kingdom. Adults without chronic pain and undergoing any elective cardiac surgery patients via sternotomy were randomly assigned to receive either usual care, pregabalin (150 mg preoperatively and twice daily for 14 postoperative days) alone, or pregabalin in combination with a 48-h postoperative infusion of intravenous ketamine at 0.1 mg · kg−1 · h−1. The primary endpoints were prevalence of clinically significant pain at 3 and 6 months after surgery, defined as a pain score on the numeric rating scale of 4 or higher (out of 10) after a functional assessment of three maximal coughs. The secondary outcomes included acute pain, opioid use, and safety measures, as well as long-term neuropathic pain, analgesic requirement, and quality of life. Results In total, 150 patients were randomized, with 17 withdrawals from treatment and 2 losses to follow-up but with data analyzed for all participants on an intention-to-treat basis. The prevalence of pain was lower at 3 postoperative months for pregabalin alone (6% [3 of 50]) and in combination with ketamine (2% [1 of 50]) compared to the control group (34% [17 of 50]; odds ratio = 0.126 [0.022 to 0.5], P = 0.0008; and 0.041 [0.0009 to 0.28], P < 0.0001, respectively) and at 6 months for pregabalin alone (6% [3 of 50]) and in combination with ketamine 0% (0 of 5) compared to the control group (28% [14 of 50]; odds ratio = 0.167 [0.029 to 0.7], P = 0.006; and 0.000 [0 to 0.24], P < 0.0001). Diplopia was more common in both active arms. Conclusions Preoperative administration of 150 mg of pregabalin and postoperative continuation twice daily for 14 days significantly lowered the prevalence of persistent pain after cardiac surgery.

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Longitudinal assessment of preoperative dexamethasone administration on cognitive function after cardiac surgery: a 4-year follow‐up of a randomized controlled trial

BMC Anesthesiology ◽

10.1186/s12871-021-01348-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sandro Glumac ◽

Goran Kardum ◽

Lidija Sodic ◽

Cristijan Bulat ◽

Ivan Covic ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Cardiac Surgery ◽

Placebo Group ◽

Cognitive Function ◽

Controlled Trial ◽

Time Interval ◽

Randomized Controlled ◽

Dexamethasone Group ◽

Postoperative Cognitive Decline

Abstract Background The pathogenesis of postoperative cognitive decline (POCD) is still poorly understood; however, the inflammatory response to surgical procedures seems likely to be involved. In addition, our recent randomized controlled trial showed that perioperative corticosteroid treatment may ameliorate early POCD after cardiac surgery. To assess the long-term effect of dexamethasone administration on cognitive function, we conducted a 4-year follow-up. Methods The patients were randomized to receive a single intravenous bolus of 0.1 mg kg− 1 dexamethasone or placebo 10 h before elective cardiac surgery. The endpoint in both groups was POCD incidence on the 6th day and four years postoperatively. Results Of the 161 patients analyzed previously, the current follow-up included 116 patients. Compared to the 62 patients in the placebo group, the 54 patients in the dexamethasone group showed a lower incidence of POCD on the 6th day (relative risk (RR), 0.510; 95 % confidence interval (CI), 0.241 to 1.079; p = 0.067, time interval also analyzed previously) and four years (RR, 0.459; 95 % CI, 0.192 to 1.100; p = 0.068) after cardiac surgery. The change in cognitive status between the two postoperative measurements was not significant (p = 0.010) among the patients in the dexamethasone group, in contrast to patients in the placebo group (p = 0.673). Conclusions Although statistical significance was not reached in the current study, the prophylactic administration of dexamethasone seems to be useful to prevent POCD development following cardiac surgery. However, further large multicenter research is needed to confirm these directions. Trial registration ClinicalTrials.gov identifier: NCT02767713 (10/05/2016).

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