Intravenous oxycodone compared to morphine for post-operative opioid-related adverse events in opioid naïve patients: a prospective randomized controlled trial

Abstract Bacground: Intravenous oxycodone compared to morphine for postoperative pain relief is controversial. The purpose of this study was to assess opioid-related adverse events of oxycodone versus morphine in opioid-naive patients after orthopaedic surgery. Methods: Patients scheduled for total hip arthroplasty under general anesthesia combined with a multimodal analgesia (acetamnophen, nonsteroidal anti-inflammatory) were randomized in a triple-blinded trial to postopertaive pain treatment with either intravenous oxycodone or morphine (potency ratio 1:1). After surgery, patients received similar drug regimen for titration in the postoperative care unit (bolus 2-3 mg, 5 min period, when pain score was >3/10) followed by an intravenous patient controlled analgesia (bolus 1 mg, lockout time 7 min) postoperatively. The primary outcome was number of patients with ≥1 opioid-related adverse events within the first 24 hours (at least one of the following complications: nausea, vomiting, respiratory depression, pruritus, urinary retention requiring evacuation, allergy, hallucination). Secondary outcomes included pain scores, opioid consumption. Patients were followed up to 4 months. Results: The intention-to-treat analysis included 241 patients with similar characteristics. There were 55 patients with at least one opioid-related adverse events in oxycodone group versus 46 in morphine group (48% vs 40%, p=0.19; relative risk= 1.22 [0.91; 1.63]). Oxycodone versus morphine requirements were respectively: 6 [0-11] versus 8 [0-12] mg (p=0.06) for titration, 15 [8-26] versus 8 [5-16] mg (p=0.001) for PCA dose, and 22 [12-37] mg versus 19 [11-28] mg for the titration and PCA accumulated consumption (p=0.048). During the first 24 hours, there were no other differences in secondary outcomes between both drugs for (respectively oxycodone versus morphine in %): nausea (15 versus 13), vomiting (5 versus 5 ), urinary retention (20 versus 12 ) and pain scores. Conclusion: This study demonstrated that oxycodone required lower doses for titration in postoperative care unit, but did not significantly reduce opioid-related adverse events within the first 24 hours compared to morphine.

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Intravenous oxycodone compared to morphine for post-operative opioid-related adverse events in opioid naïve patients: a prospective randomized controlled trial

10.21203/rs.2.16541/v1 ◽

2019 ◽

Author(s):

philippe cuvillon ◽

Sandrine Alonso ◽

Joel L’Hermite ◽

Vanessa Reubrecht ◽

Lana Zoric ◽

...

Keyword(s):

Adverse Events ◽

General Anesthesia ◽

Controlled Trial ◽

Group Versus ◽

Patient Characteristics ◽

Morphine Group ◽

Pain Scores ◽

Primary Endpoints ◽

Number Of Patients ◽

Prospective Randomized Controlled Trial

Abstract Bacground As intravenous oxycodone is as potent as morphine for pain relief, the purpose of this study was to assess opioid-related adverse events (ORAEs) of oxycodone vs morphine (1mg/1mg) in opioid naïve patients after general anesthesia and surgery.Methods Patients schedulled for total hip arthroplasty under general anesthesia were randomized in a 1:1 ratio to receive oxycodone or morphine (titration in PACU followed by intravenous PCA: bolus 1 mL, lockout time 7 min). Primary endpoints was number of patients with ≥1 ORAEs at H24 (at least one of the following complications: nausea, vomiting, respiratory depression, pruritus (itch), urinary retention requiring evacuation, allergy (skin reaction), hallucination (perception without object)). Patients were followed up to 4 months.Results Among 241 patients included in the ITT analysis, there was no difference in patient characteristics. At H24, there were 55 patients with at least one ORAEs in oxycodone group versus 46 in morphine group (48% vs 40%, p=0.19; relative risk RR (oxycodone vs morphine) = 1.22 [0.91; 1.63]). Oxycodone vs Morphine requirements were respectively: 6 [0-11] vs 8 [0-12] mg for titration in PACU (p=0.06) and 15 [8-26] vs 8 [5-16] mg during PCA period at H24 (p=0.001). The total dose of morphine administered within the first 24 h was 22 [12-37] vs 19 [11-28]mg for oxycodone (p=0.048). Pain scores (rest, movement: H0-H48) and neuropathic pain score after 4 months were similar in both groups.Conclusion Even if lower doses of oxycodone were required for PACU titration and over the first 24h, it did not lead to less ORAEs.

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Evaluating the reporting of adverse events in controlled clinical trials conducted in 2010–2015 on migraine drug treatments

Cephalalgia ◽

10.1177/0333102418759785 ◽

2018 ◽

Vol 38 (12) ◽

pp. 1885-1895

Author(s):

Peer Tfelt-Hansen ◽

Janus Kaufmann Lindqvist ◽

Thien Phu Do

Keyword(s):

Adverse Events ◽

Randomized Controlled Trials ◽

International Headache Society ◽

Controlled Trial ◽

Migraine Treatment ◽

Controlled Trials ◽

Acute Administration ◽

Drug Trials ◽

Randomized Controlled ◽

Number Of Patients

Background In 2008, the International Headache Society published guidelines on the “evaluation and registration of adverse events in clinical drug trials on migraine”. They listed seven recommendations for reporting adverse events in randomized controlled trials on migraine. The present study aimed to evaluate adherence to these recommendations, and based on the results, to recommend improvements. Methods We searched the PubMed/MEDLINE database to identify controlled trials on migraine drugs published from 2010 to 2015. For each trial, we noted whether five of the recommended parameters were presented. In addition, we noted whether adverse events were reported in abstracts. Results We identified 73 trials; 51 studied acutely administered drugs and 22 studied prophylactic drugs for migraine. The number of patients with any adverse events were reported in 74% of acute-administration and 86% of prophylactic drug trials. Only 30 (41%) of the 73 studies reported adverse events with data in the abstracts, and 27 (37%) abstracts did not mention adverse events. Conclusion Adverse events, both frequency and symptoms, should be reported to allow a fair judgement of benefit/tolerability ratio when randomized controlled trials in migraine treatment are published. Clinically significant adverse events should be included in the abstract of every randomized controlled trial in migraine treatment.

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Endosonography-guided gallbladder drainage versus percutaneous cholecystostomy in very high-risk surgical patients with acute cholecystitis: an international randomised multicentre controlled superiority trial (DRAC 1)

Gut ◽

10.1136/gutjnl-2019-319996 ◽

2020 ◽

Vol 69 (6) ◽

pp. 1085-1091 ◽

Cited By ~ 14

Author(s):

Anthony Y B Teoh ◽

Masayuki Kitano ◽

Takao Itoi ◽

Manuel Pérez-Miranda ◽

Takeshi Ogura ◽

...

Keyword(s):

High Risk ◽

Adverse Events ◽

Acute Cholecystitis ◽

Clinical Success ◽

Controlled Trial ◽

Definitive Treatment ◽

Percutaneous Cholecystostomy ◽

Gallbladder Drainage ◽

Pain Scores ◽

Very High

ObjectiveThe optimal management of acute cholecystitis in patients at very high risk for cholecystectomy is uncertain. The aim of the current study was to compare endoscopic ultrasound (EUS)-guided gallbladder drainage (EUS-GBD) to percutaneous cholecystostomy (PT-GBD) as a definitive treatment in these patients under a randomised controlled trial.DesignConsecutive patients suffering from acute calculous cholecystitis but were at very high-risk for cholecystectomy were recruited. The primary outcome was the 1-year adverse events rate. Secondary outcomes include technical and clinical success, 30-day adverse events, pain scores, unplanned readmissions, re-interventions and mortalities.ResultsBetween August 2014 to February 2018, 80 patients were recruited. EUS-GBD significantly reduced 1 year adverse events (10 (25.6%) vs 31 (77.5%), p<0.001), 30-day adverse events (5 (12.8%) vs 19 (47.5%), p=0.010), re-interventions after 30 days (1/39 (2.6%) vs 12/40 (30%), p=0.001), number of unplanned readmissions (6/39 (15.4%) vs 20/40 (50%), p=0.002) and recurrent cholecystitis (1/39 (2.6%) vs 8/40 (20%), p=0.029). Postprocedural pain scores and analgesic requirements were also less (p=0.034). The technical success (97.4% vs 100%, p=0.494), clinical success (92.3% vs 92.5%, p=1) and 30-day mortality (7.7% vs 10%, p=1) were statistically similar. The predictor to recurrent acute cholecystitis was the performance of PT-GBD (OR (95% CI)=5.63 (1.20–53.90), p=0.027).ConclusionEUS-GBD improved outcomes as compared to PT-GBD in those patients that not candidates for cholecystectomy. EUS-GBD should be the procedure of choice provided that the expertise is available after a multi-disciplinary meeting. Further studies are required to determine the long-term efficacy.Trial registration numberNCT02212717

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Vonoprazan-Based Regimen Is More Useful than PPI-Based One as a First-LineHelicobacter pyloriEradication: A Randomized Controlled Trial

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2017/4385161 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 17

Author(s):

Masafumi Maruyama ◽

Naoki Tanaka ◽

Daisuke Kubota ◽

Masayuki Miyajima ◽

Takefumi Kimura ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Adverse Events ◽

Eradication Rate ◽

Controlled Trial ◽

Eradication Therapy ◽

Group Versus ◽

Intention To Treat ◽

Randomized Controlled ◽

Primary Endpoints ◽

H Pylori

Background. A new agent, potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer advantages over conventionalH. pylorieradication therapies. We aimed to compare the eradication rate between VPZ-based treatment and PPI-based one.Methods. This randomized controlled trial was designed to assign 141 patients withH. pylori-positive gastritis to VPZ group (VPZ 20 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg twice daily for 7 days) or PPI group (rabeprazole 20 mg or lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg twice daily for 7 days). Primary endpoints were eradication rates and adverse events.Results. Seventy of 72 patients in VPZ group and 63 of 69 patients in PPI group completed the treatment after 7 days. The eradication rate was significantly higher in VPZ group than PPI group by intention-to-treat analysis (95.8% versus 69.6%,P=0.00003, 95% confidence interval [CI] 88.3-99.1% versus 57.3-80.1%) and per-protocol analysis (95.7% versus 71.4%,P=0.0002, 95% CI 88.0-99.1% versus 58.7-82.1%). The incidence of adverse events was not different between the groups (26.3% in VPZ group versus 37.7% in PPI group,P=0.15).Conclusion. VPZ-based regimen is more useful than that PPI-based regimen as a first-lineH. pylorieradication therapy.

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Buttonhole versus Stepladder Cannulation for Home Hemodialysis

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.08310718 ◽

2019 ◽

Vol 14 (3) ◽

pp. 403-410 ◽

Cited By ~ 2

Author(s):

Shih-Han S. Huang ◽

Jennifer MacRae ◽

Dana Ross ◽

Rameez Imtiaz ◽

Brittany Hollingsworth ◽

...

Keyword(s):

Controlled Trial ◽

Venous Catheter ◽

Primary Objective ◽

Home Hemodialysis ◽

Training Time ◽

Research Priority ◽

Pain Scores ◽

Number Of Patients ◽

Cannulation Technique ◽

Data Linkages

Background and objectivesCanadian home hemodialysis guidelines highlight the potential differences in complications associated with arteriovenous fistula (AVF) cannulation technique as a research priority. Our primary objective was to determine the feasibility of randomizing patients with ESKD training for home hemodialysis to buttonhole versus stepladder cannulation of the AVF. Secondary objectives included training time, pain with needling, complications, and cost by cannulation technique.Design, setting, participants, & measurementsAll patients training for home hemodialysis at seven Canadian hospitals were assessed for eligibility, and demographic information and access type was collected on everyone. Patients who consented to participate were randomized to buttonhole or stepladder cannulation technique. Time to train for home hemodialysis, pain scores on cannulation, and complications over 12 months was recorded. For eligible but not randomized patients, reasons for not participating in the trial were documented.ResultsPatient recruitment was November 2013 to November 2015. During this time, 158 patients began training for home hemodialysis, and 108 were ineligible for the trial. Diabetes mellitus as a cause of ESKD (31% versus 12%) and central venous catheter use (74% versus 6%) were more common in ineligible patients. Of the 50 eligible patients, 14 patients from four out of seven sites consented to participate in the study (28%). The most common reason for declining to participate was a strong preference for a particular cannulation technique (33%). Patients randomized to buttonhole versus stepladder cannulation required a shorter time to complete home hemodialysis training. We did not observe a reduction in cannulation pain or complications with the buttonhole method. Data linkages for a formal cost analysis were not conducted.ConclusionsWe were unable to demonstrate the feasibility of conducting a randomized, controlled trial of buttonhole versus stepladder cannulation in Canada with a sufficient number of patients on home hemodialysis to be able to draw meaningful conclusions.

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A comparison of accuracy and safety between stem-first and cup-first total hip arthroplasty: a prospective randomised controlled trial

Hip International ◽

10.1177/11207000211039767 ◽

2021 ◽

pp. 112070002110397

Author(s):

Kentaro Iwakiri ◽

Yoichi Ohta ◽

Yukihide Minoda ◽

Akio Kobayashi ◽

Hiroaki Nakamura

Keyword(s):

Randomised Controlled Trial ◽

Total Hip Arthroplasty ◽

Adverse Events ◽

Hip Arthroplasty ◽

Operative Time ◽

Controlled Trial ◽

Total Hip ◽

Combined Anteversion ◽

Secondary Outcomes ◽

Randomised Controlled

Background: The combined anteversion theory to prevent impingement in total hip arthroplasty (THA) has been proposed. However, because stem-anteversion is influenced by the native femoral anteversion and the stem flexion/extension angle, it is often difficult to adjust stem anteversion during surgery. Therefore, the stem-first (combined anteversion) technique may be useful to adjust and achieve appropriate cup anteversion during surgery with respect to the implanted stem anteversion angle. However, the technique may adversely affect cup or stem angle accuracy and result in intra-operative bleeding, post-operative adverse events, and prolonged operative time. It is inconclusive whether either the stem-first or cup-first technique is safe or accurate. Therefore, this study assessed the accuracy and safety of stem-first THA compared to those of cup-first THA. Materials and methods: This prospective randomised controlled trial analysed 114 patients who were randomly divided into 2 groups (stem-first group: n = 57, cup-first group (control group): n = 57). Primary outcomes included cup and stem angle, the discrepancies from the targeted angle and combined anteversion (evaluated via CT at 3 months postoperatively). Secondary outcomes included intraoperative blood loss, operative time, WOMAC, and adverse events. Results: There were no significant differences in age, gender, BMI or in the primary and secondary outcomes between the 2 groups. Conclusions: Performing stem-first in THA did not adversely affect cup and stem angle accuracy, or result in intraoperative bleeding, prolongation of operative time, or postoperative adverse events. Thus, performing stem-first may be advantageous for achieving combined anteversion theory. Trial registration: University Hospital Medical Information Network (UMIN) registration number UMIN000025189.

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A randomized controlled trial with everolimus for IQ and autism in tuberous sclerosis complex

Neurology ◽

10.1212/wnl.0000000000007749 ◽

2019 ◽

Vol 93 (2) ◽

pp. e200-e209 ◽

Cited By ~ 16

Author(s):

Iris E. Overwater ◽

André B. Rietman ◽

Sabine E. Mous ◽

Karen Bindels-de Heus ◽

Dimitris Rizopoulos ◽

...

Keyword(s):

Intellectual Disability ◽

Adverse Events ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Behavioral Problems ◽

Neuropsychological Functioning ◽

Controlled Trial ◽

Full Scale ◽

Neuropsychological Deficits ◽

Secondary Outcomes

ObjectiveTo investigate whether mammalian target of rapamycin inhibitor everolimus can improve intellectual disability, autism, and other neuropsychological deficits in children with tuberous sclerosis complex (TSC).MethodsIn this 12-month, randomized, double-blind, placebo-controlled trial, we attempted to enroll 60 children with TSC and IQ <80, learning disability, special schooling, or autism, aged 4–17 years, without intractable seizures to be assigned to receive everolimus or placebo. Everolimus was titrated to blood trough levels of 5–10 ng/mL. Primary outcome was full-scale IQ; secondary outcomes included autism, neuropsychological functioning, and behavioral problems.ResultsThirty-two children with TSC were randomized. Intention-to-treat analysis showed no benefit of everolimus on full-scale IQ (treatment effect −5.6 IQ points, 95% confidence interval −12.3 to 1.0). No effect was found on secondary outcomes, including autism and neuropsychological functioning, and questionnaires examining behavioral problems, social functioning, communication skills, executive functioning, sleep, quality of life, and sensory processing. All patients had adverse events. Two patients on everolimus and 2 patients on placebo discontinued treatment due to adverse events.ConclusionsEverolimus did not improve cognitive functioning, autism, or neuropsychological deficits in children with TSC. The use of everolimus in children with TSC with the aim of improving cognitive function and behavior should not be encouraged in this age group.Clinicaltrials.gov identifierNCT01730209.Classification of evidenceThis study provides Class I evidence that for children with TSC, everolimus does not improve intellectual disability, autism, behavioral problems, or other neuropsychological deficits.

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Adenoma detection with Endocuff colonoscopy versus conventional colonoscopy: a multicentre randomised controlled trial

Gut ◽

10.1136/gutjnl-2015-310097 ◽

2015 ◽

Vol 66 (3) ◽

pp. 438-445 ◽

Cited By ~ 61

Author(s):

SC van Doorn ◽

M van der Vlugt ◽

ACTM Depla ◽

CA Wientjes ◽

RC Mallant-Hent ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Colorectal Neoplasia ◽

Controlled Trial ◽

Group Versus ◽

Conventional Colonoscopy ◽

P Value ◽

Adenoma Detection ◽

Number Of Patients ◽

Advanced Adenomas ◽

Randomised Controlled

Background and aimsColonoscopy is the current reference standard for the detection of colorectal neoplasia, but nevertheless adenomas remain undetected. The Endocuff, an endoscopic cap with plastic projections, may improve colonic visualisation and adenoma detection. The aim of this study was to compare the mean number of adenomas per patient (MAP) and the adenoma detection rate (ADR) between Endocuff-assisted colonoscopy (EAC) and conventional colonoscopy (CC).MethodsWe performed a multicentre, randomised controlled trial in five hospitals and included fecal immonochemical test (FIT)-positive screening participants as well as symptomatic patients (>45 years). Consenting patients were randomised 1:1 to EAC or CC. All colonoscopies were performed by experienced colonoscopists (≥500 colonoscopies) who were trained in EAC. All colonoscopy quality indicators were prospectively recorded.FindingsOf the 1063 included patients (52% male, median age 65 years), 530 were allocated to EAC and 533 to CC. More adenomas were detected with EAC, 722 vs 621, but the gain in MAP was not significant: on average 1.36 per patient in the EAC group versus 1.17 in the CC group (p=0.08). In a per-protocol analysis, the gain was 1.44 vs 1.19 (p=0.02), respectively. In the EAC group, 275 patients (52%) had one or more adenomas detected versus 278 in the CC group (52%; p=0.92). For advanced adenomas these numbers were 109 (21%) vs 117 (22%). The adjusted caecal intubation rate was lower with EAC (94% vs 99%; p<0.001), however when allowing crossover from EAC to CC, they were similar in both groups (98% vs 99%; p value=0.25).InterpretationThough more adenomas are detected with EAC, the routine use of Endocuff does not translate in a higher number of patients with one or more adenomas detected. Whether increased detection ultimately results in a lower rate of interval carcinomas is not yet known.Trial registration numberhttp://www.trialregister.nlDutch Trial Register: NTR3962.

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Early administration of oral morphine to orthopedic patients after surgery

Journal of Opioid Management ◽

10.5055/jom.2006.0014 ◽

2006 ◽

Vol 2 (2) ◽

pp. 88 ◽

Cited By ~ 10

Author(s):

Ruth Zaslansky, DSc ◽

Elon Eisenberg, MD ◽

Bezalel Peskin, MD ◽

Elliot Sprecher, PhD ◽

Daniel N. Reis, MD ◽

...

Keyword(s):

Postoperative Pain ◽

Adverse Effects ◽

Treatment Guidelines ◽

Pain Treatment ◽

Oral Morphine ◽

Immediate Release ◽

Treatment Method ◽

Pain Scores ◽

Number Of Patients ◽

Average Pain

Current pain treatment guidelines advise against providing analgesics for postoperative pain using intramuscular injections, as this generally provides poor pain relief. However, this route remains the most prevalent treatment method. Intravenous or epidural patient-controlled-analgesia methods reduce pain effectively but are expensive, labor intensive, and available to only a limited number of patients. We propose administering the analgesics using oral analgesics and have developed a simple protocol for treating postoperative pain by use of oral morphine. After a variety of orthopedic surgeries, patients were given “around-the-clock,” oral, immediate-release morphine. Efficacy of the treatment (pain scores and adverse effects) was assessed 24 ± 2 hours after surgery. Data were collected prospectively from 95 patients, who received an average of 61 ± 30 (SD) mg morphine. Average pain scores were 2.4/10 (± 1.4) at rest and 4.0/10 (± 1.4) during movement in bed. Nausea and vomiting, the most common adverse effects, were reported by 22 (23 percent) patients. Naloxone was not administered to any of the patients. Oral morphine given in the early postoperative time to patients after a variety of orthopedic surgeries was effective and safe.

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Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial

European Respiratory Journal ◽

10.1183/13993003.03725-2020 ◽

2020 ◽

pp. 2003725

Author(s):

Patricia R. M. Rocco ◽

Pedro L. Silva ◽

Fernanda F. Cruz ◽

Marco Antonio C. M. Junior ◽

Paulo F. G. M. M. Tierno ◽

...

Keyword(s):

Viral Load ◽

Adverse Events ◽

Controlled Trial ◽

Nasopharyngeal Swab ◽

Serious Adverse Events ◽

Double Blind ◽

Symptom Resolution ◽

Days Of Therapy ◽

Secondary Outcomes

Nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on SARS-CoV-2 infection. In a multicenter, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of Covid-19 symptoms (dry cough, fever, and/or fatigue) were enrolled. After confirmation of SARS-CoV2 infection by RT-PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, TID, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation, and hospitalisation rate. Adverse events were also assessed. From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median time from symptom onset to first dose of study drug was 5 (4–5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was also reduced after nitazoxanide compared to placebo (p=0.006). The percent viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed. In patients with mild Covid-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.

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