A randomized, controlled, feasibility study of RD-X19 in patients with mild-to-moderate COVID-19 in the outpatient setting

These studies aimed to further understand the antiviral effects of safe, visible light and demonstrate a therapeutic effect of an investigational treatment device for outpatients with mild to moderate COVID-19. RD-X19 is a handheld medical device precisely engineered to emit blue light through the oral cavity to target the oropharynx and surrounding tissues. At doses that are well-tolerated in an in vitro human epithelial tissue model, the monochromatic visible light delivered by RD-X19 results in light-initiated expression of IL-1α and IL-1β cytokines with corresponding inhibition of SARS-CoV-2 replication. A randomized, double-blind, sham-controlled early feasibility study using the investigational device enrolled 31 subjects with a positive SARS-CoV-2 antigen test and possessing at least two moderate COVID-19 signs and symptoms. Subjects were randomized 2:1 (RD-X19 to sham), treated twice daily for four days, and evaluated over one week. Prespecified outcome measures included assessments of SARS-CoV-2 viral load and clinical assessments of COVID-19. There were no local application site reactions and no device-related adverse events. The time-weighted average change in log viral load throughout the study demonstrated a favorable reduction for RD-X19 compared to sham and at the end of study the mean change in log10 viral load was -3.29 for RD-X19 and -1.81 for sham at Day 8, demonstrating a treatment benefit of -1.48 [95% confidence internal (CI), -2.88 to -0.071]. Among the clinical outcome measures, differences between RD-X19 and sham were also observed, with a 57-hour reduction of median time to sustained resolution of COVID-19 signs and symptoms.

Download Full-text

Efficacy of Two Siddha Poly herbal Decoctions, Nilavembu Kudineer and Kaba Sura Kudineer, along with Standard Allopathy Treatment in the Management of Mild to Moderate Symptomatic COVID-19 Patients -a Double-Blind, Placebo Controlled, Clinical Trial

10.21203/rs.3.rs-604520/v1 ◽

2021 ◽

Author(s):

Anurag Srivast ◽

Manickavasagam Rengaraju ◽

Saurabh Srivast ◽

Vimal Narayanan ◽

Vivek Gupta ◽

...

Keyword(s):

Clinical Trial ◽

Viral Load ◽

Adverse Events ◽

Hospital Stay ◽

Outcome Measures ◽

Double Blind ◽

Double Blind Placebo ◽

Function Test ◽

Stay Time ◽

Time Reduction

Abstract Background & Aim: Globally, the ongoing pursuit in exploring an effective drug to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has not met with significant success till date. Indian traditional medicines, especially poly herbal formulations like Nilavembu Kudineer (NVK) and Kaba Sura Kudineer (KSK) of the Siddha system of medicine have been used as public health interventions for controlling viral epidemics like dengue and Chikungunya. These traditional therapies have been found safe, effective, and widely accepted. The current study evaluates the comparative efficacy of NVK and KSK as opposed to the placebo, in the management of mild to moderate COVID-19 disease. Methods: The study was a double blind, placebo controlled comparative clinical trial, with the primary objective of determining the efficacy of KSK and NVK. Patients (n=125) diagnosed with mild to moderate COVID-19 symptoms were enrolled in the study over a period of 4 months (Aug 2020 – Dec 2020). Participants were randomised into 3 arms; placebo-decaffeinated tea in Arm 1; NVK in Arm II and KSK in Arm III. Each arm received 60 ml of the respective treatment twice a day, post morning and evening meals, along with standard Allopathy treatment for a maximum of 10 days. The main outcome measures of the study were the reduction in SARS-CoV-2 viral load, hospital stay, and time taken by the patients to become asymptomatic from symptomatic. Efficacy assessments included clinical symptoms (fever, cough and breathlessness) each day and real-time reverse transcription-polymerase chain reaction (RT-PCR),liver function test (LFT), renal function test (RFT) and electrolytes and electrocardiogram (ECG) at baseline (Day 0), Day 3, 6 and 10. Post treatment, participants were followed up for 30 days via phone for adverse effects if any. Effects of drugs on inflammatory markers (IL6,) at the end of treatment were also recorded. Adverse events (AE) were monitored throughout the study. Results: The results revealed that when compared to patients in placebo arm, those in NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and the time taken to become symptomatic from asymptomatic. Out of 125 COVID-19 patients recruited, 120 completed the study; two from the placebo group developed severe symptoms and were shifted to intensive care unit (ICU) and three patients from arms II and III withdrew from the study. The mean age of females (n=60) and males (n=60) enrolled was between 40.2 and 44.3 years respectively. Results were more promising for all the patients in NVK and KSK arms as all enrolled participants (100%) under this group got discharged by day 6 as compared to only 42.5% (n=17) from placebo groupon that day. The hospital stay time for patients in Arm I, was significantly longer (Mean [SD]=8.4 [2.0] days) as compared to the Arm II and III (Mean [SD]=4.7 [1.5] and 4.2 [1.5] days respectively (Kruskal Wallis test, p=0.0001).Patients in the three groups took a significantly different number of days to become asymptomatic. While Arm II and III patients took mean 2.5 and 1.7 days respectively, Arm I, patients took a mean of 4.2 days (Kruskal Wallis test, p=0.0001). In all, two adverse events were recorded, one for vomiting and one for diarrhoea lasting a day in Arm I & Arm II respectively. Mean value of interleukin-6 (IL6) was significantly different in comparison to the placebo-decaffeinated tea arm (NVK=2.6 and KSK=2.2, Placebo=4.0, p=0.02).The other blood biochemical parameters like C-Reactive Protein (CRP), Lactate Dehydrogenase (LDH), Ferritin and D-Dimer that were analysed at the baseline and at the time of discharge from hospital, were not significantly different in the three arms. Conclusion: NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2 and time taken for patients to become asymptomatic from symptomatic, when compared to the placebo (decaffeinated tea).The primary outcome measures of KSK arm were significantly better than that in the NVK arm.

Download Full-text

A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial of Presatovir for the Treatment of Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic-Cell Transplant Recipients

Clinical Infectious Diseases ◽

10.1093/cid/ciz1166 ◽

2019 ◽

Vol 71 (11) ◽

pp. 2777-2786 ◽

Cited By ~ 14

Author(s):

Roy F Chemaly ◽

Sanjeet S Dadwal ◽

Anne Bergeron ◽

Per Ljungman ◽

Yae-Jean Kim ◽

...

Keyword(s):

Viral Load ◽

Respiratory Tract ◽

Weighted Average ◽

Cell Transplant ◽

Upper Respiratory Tract ◽

Hematopoietic Cell Transplant ◽

Double Blind ◽

Time Weighted Average ◽

Upper Respiratory ◽

Syncytial Virus

Abstract Background Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections. Methods Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/μL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28. Results From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, −0.33 log10 copies/mL; 95% confidence interval [CI] −.64 to −.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22–1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo. Conclusions Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia. Clinical Trials Registration NCT02254408; EUDRA-CT#2014-002474-36.

Download Full-text

REGEN-COV Antibody Cocktail in Outpatients with Covid-19

10.1101/2021.06.09.21257915 ◽

2021 ◽

Author(s):

David Weinreich ◽

Sumathi Sivapalasingam ◽

Thomas Norton ◽

Shazia Ali ◽

Haitao Gao ◽

...

Keyword(s):

Viral Load ◽

Relative Risk ◽

Phase 1 ◽

Serum Antibody ◽

Weighted Average ◽

Baseline Viral Load ◽

Double Blind ◽

Group 2 ◽

Antibody Cocktail ◽

Group 1

Background: REGEN-COV (casirivimab and imdevimab) antibody cocktail reduced SARS-CoV-2 viral load in descriptive analyses of the first 275 Covid-19 outpatients in the phase 1/2 portion of an ongoing double-blind, seamless phase 1/2/3 trial. Methods: This final analysis of the phase 1/2 portion includes 799 patients: 275 (group-1) and 524 (group-2). Patients were randomized (1:1:1) to placebo, 2400mg REGEN-COV, or 8000mg REGEN-COV, and characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive/negative). Efficacy was assessed in patients with a positive baseline RT-qPCR result; safety was assessed in all treated patients. Prespecified hierarchical analyses of virologic endpoints in group-2 were performed to confirm previously reported descriptive analyses from group-1. The proportion of patients with ≥1 Covid-19-related medically-attended visit (MAV) through day 29 was assessed in group-1+2. Results: Time-weighted average reduction in viral load (log10 copies/ml) through day 7 was significantly greater with REGEN-COV (combined 2400mg+8000mg dose groups) versus placebo in patients with baseline viral load >107 copies/ml (prespecified primary endpoint): -0.68 (95% CI, -0.94 to -0.41; P<0.0001). This reduction was -0.73 (P<0.0001) in serum antibody-negative patients and -0.36 (P=0.0003) in the overall population. Proportions of patients with ≥1 Covid-19-related MAV were 2.8% (12/434) with REGEN-COV versus 6.5% (15/231) with placebo (P=0.024; relative risk reduction=57%), with greater relative risk reductions in MAVs in patients with ≥1 risk factor for hospitalization (71%). Adverse events were similar across groups. Conclusions: REGEN-COV treatment of outpatients significantly reduced SARS-CoV-2 viral load and Covid-19-related medically-attended visits. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.)

Download Full-text

Protocol for a prospective double-blind, randomised, placebo-controlled feasibility trial of octreotide infusion during liver transplantation

BMJ Open ◽

10.1136/bmjopen-2021-055864 ◽

2021 ◽

Vol 11 (12) ◽

pp. e055864

Author(s):

Jeremy Fabes ◽

Gareth Ambler ◽

Bina Shah ◽

Norman R Williams ◽

Daniel Martin ◽

...

Keyword(s):

Quality Of Life ◽

Liver Transplantation ◽

Outcome Measures ◽

Feasibility Study ◽

Study Design ◽

Efficacy And Safety ◽

Double Blind ◽

University College ◽

University College London

IntroductionLiver transplantation is a complex operation that can provide significant improvements in quality of life and survival to the recipients. However, serious complications are common and include major haemorrhage, hypotension and renal failure. Blood transfusion and the development of acute kidney injury lead to both short-term and long-term poor patient outcomes, including an increased risk of death, graft failure, length of stay and reduced quality of life. Octreotide may reduce the incidence of renal dysfunction, perioperative haemorrhage and enhance intraoperative blood pressure. However, octreotide does have risks, including resistant bradycardia, hyperglycaemia and hypoglycaemia and QT prolongation. Hence, a randomised controlled trial of octreotide during liver transplantation is needed to determine the cost-efficacy and safety of its use; this study represents a feasibility study prior to this trial.Methods and analysisWe describe a multicentre, double-blind, randomised, placebo-controlled feasibility study of continuous infusion of octreotide during liver transplantation surgery. We will recruit 30 adult patients at two liver transplant centres. A blinded infusion during surgery will be administered in a 2:1 ratio of octreotide:placebo. The primary outcomes will determine the feasibility of this study design. These include the recruitment ratio, correct administration of blinded study intervention, adverse event rates, patient and clinician enrolment refusal and completion of data collection. Secondary outcome measures of efficacy and safety will help shape future trials by assessing potential primary outcome measures and monitoring safety end points. No formal statistical tests are planned. This manuscript represents study protocol number 1.3, dated 2 June 2021.Ethics and disseminationThis study has received Research Ethics Committee approval. The main study outcomes will be submitted to an open-access journal.Trial sponsorThe Joint Research Office, University College London, UK.Neither the sponsor nor the funder have any role in study design, collection, management, analysis and interpretation of data, writing of the study report or the decision to submit the report for publication.Trial registrationThe study is registered with ClinicalTrials.gov (NCT04941911) with recruitment due to start in August 2021 with anticipated completion in July 2022.Clinical trials unitSurgical and Interventional Group, Division of Surgery & Interventional Science, University College London.

Download Full-text

Phase 2 dose-ranging study of the virologic efficacy and safety of the combination COVID-19 antibodies casirivimab and imdevimab in the outpatient setting

10.1101/2021.11.09.21265912 ◽

2021 ◽

Author(s):

Cynthia Portal Celhay ◽

Eduardo Forleo-Neto ◽

Will Eagan ◽

Bret J. Musser ◽

John D. Davis ◽

...

Keyword(s):

Viral Load ◽

Weighted Average ◽

Study Drug ◽

Outpatient Setting ◽

Controlled Study ◽

Serious Adverse Events ◽

Double Blind ◽

Injection Site Reactions ◽

Grade 3 ◽

Mean Differences

Background: The monoclonal antibody combination casirivimab and imdevimab (REGEN-COV®) reduced viral load, hospitalisation, or death when administered 1:1 as an intravenous (IV) dose ≥1200 mg in a phase 3 COVID-19 outpatient study. Availability of subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients. Methods: This is a double-blind, placebo-controlled study of SARS-CoV-2-infected outpatients who were asymptomatic, or symptomatic but without risk factors for severe COVID-19. Patients were randomised to single IV dose (517 patients) of REGEN-COV 300, 600, 1200 or 2400 mg or placebo; or a single SC dose (286 patients) of REGEN-COV 600 or 1200 mg or placebo. The primary endpoint was time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative to SARS-CoV-2 at baseline. Findings: All REGEN-COV treatments showed significant (p<0.001 versus pooled placebo) virologic reduction through day 7. Least-squares mean differences in TWACB viral load for the treatments versus placebo ranged from –0·56 to –0.71 log10 copies/mL. Each REGEN-COV treatment showed significant (p<0.001 versus pooled placebo) and similar virologic reduction through day 7. There were no safety concerns, dose-related safety findings, grade ≥2 infusion related/hypersensitivity reactions, grade ≥3 injection-site reactions, nor fatalities. Two serious adverse events not related to COVID-19 or the study drug were reported. Interpretation: In asymptomatic and low-risk symptomatic SARS-CoV-2-infected outpatients seronegative for antibodies against SARS-CoV-2 at baseline, REGEN-COV significantly and comparably reduced viral load at all IV and SC doses.

Download Full-text

Involving frail older patients in identifying outcome measures for transitional care—a feasibility study

Research Involvement and Engagement ◽

10.1186/s40900-021-00288-9 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Troels Kjærskov Hansen ◽

Annesofie Lunde Jensen ◽

Else Marie Damsgaard ◽

Tone Maria Mørck Rubak ◽

Mikkel Erik Juul Jensen ◽

...

Keyword(s):

Health Care ◽

Outcome Measures ◽

Feasibility Study ◽

Thematic Analysis ◽

Older Patients ◽

Public Involvement ◽

Transitional Care ◽

Care Transitions ◽

Level Of Involvement ◽

Relevant Outcome

Abstract Background During care transitions, the older (75+) patient’s agenda can easily be missed. To counteract this, involving patients in shared clinical decision making has proven to be of great value. Likewise, involving patients and other stakeholders as researchers is gaining ground. Patient and public involvement (PPI) in research entails many benefits, for example, by bringing further insight from those with lived experiences of being ill. There are various challenges associated with involving some older patients, for example frailty, cognitive impairment and other chronic illnesses. To the best of our knowledge, there are only a few examples of initiatives involving older patients beyond research participation. The feasibility of involving frail older patients during an ongoing care transition from hospital to primary health care remains unknown. To investigate the feasibility of including older frail patients, their relatives and health care professionals (HCPs) as co-researchers, we established a study with increasingly demanding levels of patient involvement to identify relevant outcome measures for future transitional care research. Methods The study was a pragmatic, qualitative feasibility study. The involved individuals were frail older patients, their relatives and HCPs. Patients and their relatives were interviewed, while the interviewer made reflective notes. A thematic analysis was made. Relatives and HCPs discussed the themes to identify relevant outcome measures and potentially co-create new patient-reported outcome measures (PROMs) for use in future transitional care studies. The feasibility was evaluated according to six involvement steps. The level of involvement was evaluated using the five-levelled Health Canada Public Involvement Continuum (HCPIC). Results In total, eight patients, five relatives and three HCPs were involved in the study. Patients were involved in discussing care transitions (HCPIC level 3), while some relatives were engaged (HCPIC level 4) in forming PROMs. The partnership level of involvement (HCPIC level 5) was not reached. The thematic analysis and the subsequent theme discussion successfully formed PROMs. The key PROMs were related to care, transparency and the relatives’ roles in the transitional care process. Conclusions When applying a pragmatic involvement approach, frail older patients can be successfully involved in identifying relevant transitional care outcome measures; however, involving these patients as fellow researchers seems infeasible. To maintain involvement, supportive relatives are essential. Useful experiences for future research involvement of this vulnerable group were reported, arguing that patient participation has the potential to become inherent in future geriatric research.

Download Full-text

Treatment benefit among migraine patients taking fremanezumab: results from a post hoc responder analysis of two placebo-controlled trials

The Journal of Headache and Pain ◽

10.1186/s10194-020-01212-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Stephen D. Silberstein ◽

Joshua M. Cohen ◽

Ronghua Yang ◽

Sanjay K. Gandhi ◽

Evelyn Du ◽

...

Keyword(s):

Clinical Trials ◽

Medication Use ◽

Two Phase ◽

Double Blind ◽

Treatment Benefit ◽

Mean Values ◽

Treatment Benefits ◽

Acute Headache ◽

Post Hoc ◽

Insight Into

Abstract Background Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, including the fully humanized monoclonal antibody (IgG2Δa) fremanezumab, have demonstrated safety and efficacy for migraine prevention. Clinical trials include responders and nonresponders; efficacy outcomes describe mean values across both groups and thus provide little insight into the clinical benefit in responders. Clinicians and their patients want to understand the extent of clinical improvement in patients who respond. This post hoc analysis of fremanezumab treatment attempts to answer this question: what is the benefit in subjects who responded to treatment during the two, phase 3 HALO clinical trials? Methods We included subjects with episodic migraine (EM) or chronic migraine (CM) who received fremanezumab quarterly (675 mg/placebo/placebo) or monthly (EM: 225 mg/225 mg/225 mg; CM: 675 mg/225 mg/225 mg) during the 12-week randomized, double-blind, placebo-controlled HALO EM and HALO CM clinical trials. EM and CM responders were defined as participants with a reduction of ≥ 2 or ≥ 4 monthly migraine days, respectively. Treatment benefits evaluated included reductions in monthly migraine days, acute headache medication use, and headache-related disability, and changes in health-related quality of life (HRQoL). Results Overall, 857 participants from the HALO trials were identified as responders (EM: 429 [73.8%]; CM: 428 [56.7%]). Reductions in the monthly average number of migraine days were greater among EM (quarterly: 5.4 days; monthly: 5.5 days) and CM (quarterly: 8.7 days; monthly: 9.1 days) responders compared with the overall population. The proportion of participants achieving ≥ 50% reduction in the average monthly number of migraine days was also greater in responders (EM: quarterly, 59.8%; monthly, 63.7%; CM: quarterly, 52.8%; monthly, 59.0%) than in the overall population. Greater reductions in the average number of days of acute headache medication use, greater reductions in headache-related disability scores, and larger improvements in HRQoL were observed among EM and CM responders compared with the overall populations. Conclusions Fremanezumab responders achieved clinically meaningful improvements in all outcomes. The magnitude of improvements with fremanezumab across efficacy outcomes was far greater in responders than in the overall trial population, providing insight into expected treatment benefits in participants who respond to fremanezumab in clinical practice. Trial registration ClinicalTrials.gov identifiers: NCT02629861 (HALO EM) and NCT02621931 (HALO CM).

Download Full-text

Low Dose Ketamine Infusion for Comorbid Posttraumatic Stress Disorder and Chronic Pain: A Randomized Double-Blind Clinical Trial

Chronic Stress ◽

10.1177/2470547020981670 ◽

2020 ◽

Vol 4 ◽

pp. 247054702098167

Author(s):

Alisher R. Dadabayev ◽

Sonalee A. Joshi ◽

Mariam H. Reda ◽

Tamar Lake ◽

Mark S. Hausman ◽

...

Keyword(s):

Posttraumatic Stress Disorder ◽

Chronic Pain ◽

Posttraumatic Stress ◽

Outcome Measures ◽

Low Dose ◽

Stress Disorder ◽

Double Blind ◽

Impact Of Event Scale ◽

Event Scale ◽

Ketamine Infusion

Objective To date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with posttraumatic stress disorder (PTSD), are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike. Among patients with chronic pain (CP) about one third experience comorbid PTSD, which further complicates their already challenging pharmacological regimens. Low dose ketamine infusion has shown promise in PTSD, and in treatment of CP, however they have not been studied in comorbid population and under rigorous control conditions. Methods We compared the effects of a single dose of either ketamine (0.5 mg/kg) or ketorolac (15 mg) over a 40-minute of IV infusion in CP patients with and without PTSD, in double blind, randomized study. Measures were collected before, during, one day and seven days after the infusion. A planned sample size of 40 patients randomly assigned to treatment order was estimated to provide 80% power to detect a hypothesized treatment difference after the infusion. Main Outcome and Measures: The primary outcome measures were change in PTSD symptom severity assessed with the Impact of Event Scale–Revised (IES-R) and Visual Analogue Scale (VAS) for pain administered by a study clinician 24 hours post infusion. Secondary outcome measures included Impact of Event Scale–Revised (IES-R), VAS and Brief Pain Inventory (Short Form) for pain 1 week after the infusion. Results Both treatments offered comparable improvement of PTSD and CP symptoms that persisted for 7 days after the infusion. Patients with comorbid PTSD and CP experienced less dissociative side effects compared to the CP group. Surprisingly, ketorolac infusion resulted in dissociative symptoms in CP patients only. Conclusions This first prospective study comparing effects of subanesthetic ketamine versus ketorolac infusions for comorbid PTSD and CP, suggests that both ketamine and ketorolac might offer meaningful and durable response for both PTSD and CP symptoms.

Download Full-text

Methotrimeprazine versus haloperidol in palliative care patients with cancer-related nausea: a randomised, double-blind controlled trial

BMJ Open ◽

10.1136/bmjopen-2019-029942 ◽

2019 ◽

Vol 9 (9) ◽

pp. e029942 ◽

Cited By ~ 2

Author(s):

Janet Rea Hardy ◽

Helen Skerman ◽

Jennifer Philip ◽

Phillip Good ◽

David C Currow ◽

...

Keyword(s):

Palliative Care ◽

Outcome Measures ◽

Controlled Trial ◽

Response Rates ◽

Complete Response ◽

Response To Treatment ◽

Secondary Outcome ◽

Double Blind ◽

Intention To Treat ◽

Point Reduction

ObjectivesMethotrimeprazine is commonly used for the management of nausea but never tested formally against other drugs used in this setting. The aim was to demonstrate superior antiemetic efficacy.DesignDouble-blind, randomised, controlled trial of methotrimeprazine versus haloperidol.Setting11 palliative care sites in Australia.ParticipantsParticipants were >18 years, had cancer, an average nausea score of ≥3/10 and able to tolerate oral medications. Ineligible patients had acute nausea related to treatment, nausea for which a specific antiemetic was indicated, were about to undergo a procedure or had received either of the study drugs or a change in glucocorticoid dose within the previous 48 hours.InterventionsBased on previous studies, haloperidol was used as the control. Participants were randomised to encapsulated methotrimeprazine 6·25 mg or haloperidol 1·5 mg one time or two times per day and assessed every 24 hours for 72 hours.Main outcome measuresA ≥two-point reduction in nausea score at 72 hours from baseline. Secondary outcome measures were as follows: complete response at 72 hours (end nausea score less than 3), response at 24 and 48 hours, vomiting episodes, use of rescue antiemetics, harms and global impression of change.ResultsResponse to treatment at 72 hours was 75% (44/59) in the haloperidol (H) arm and 63% (36/57) in the methotrimeprazine (M) arm with no difference between groups (intention-to-treat analysis). Complete response rates were 56% (H) and 51% (M). In theper protocolanalysis, there was no difference in response rates: (85% (44/52) (H) and 74% (36/49) (M). Completeper protocolresponse rates were 64% (H) and 59% (M). Toxicity worse than baseline was minimal with a trend towards greater sedation in the methotrimeprazine arm.ConclusionThis study did not demonstrate any difference in response rate between methotrimeprazine and haloperidol in the control of nausea.Trial registration numberACTRN 12615000177550.

Download Full-text

Treatment of thoracolumbar burst fractures: extended follow-up of a randomized clinical trial comparing orthosis versus no orthosis

Journal of Neurosurgery Spine ◽

10.3171/2016.11.spine161031 ◽

2017 ◽

Vol 27 (1) ◽

pp. 42-47 ◽

Cited By ~ 12

Author(s):

Jennifer C. Urquhart ◽

Osama A. Alrehaili ◽

Charles G. Fisher ◽

Alyssa Fleming ◽

Parham Rasoulinejad ◽

...

Keyword(s):

Outcome Measures ◽

Weighted Average ◽

Average Treatment Effect ◽

Secondary Outcome ◽

Thoracolumbar Burst Fractures ◽

Treatment Comparison ◽

Average Treatment ◽

Burst Fractures ◽

Time Weighted Average

OBJECTIVEA multicenter, prospective, randomized equivalence trial comparing a thoracolumbosacral orthosis (TLSO) to no orthosis (NO) in the treatment of acute AO Type A3 thoracolumbar burst fractures was recently conducted and demonstrated that the two treatments following an otherwise similar management protocol are equivalent at 3 months postinjury. The purpose of the present study was to determine whether there was a difference in long-term clinical and radiographic outcomes between the patients treated with and those treated without a TLSO. Here, the authors present the 5- to 10-year outcomes (mean follow-up 7.9 ± 1.1 years) of the patients at a single site from the original multicenter trial.METHODSBetween July 2002 and January 2009, a total of 96 subjects were enrolled in the primary trial and randomized to two groups: TLSO or NO. Subjects were enrolled if they had an AO Type A3 burst fracture between T-10 and L-3 within the previous 72 hours, kyphotic deformity < 35°, no neurological deficit, and an age of 16–60 years old. The present study represents a subset of those patients: 16 in the TLSO group and 20 in the NO group. The primary outcome measure was the Roland Morris Disability Questionnaire (RMDQ) score at the last 5- to 10-year follow-up. Secondary outcome measures included kyphosis, satisfaction, the Numeric Rating Scale for back pain, and the 12-Item Short-Form Health Survey (SF-12) Mental and Physical Component Summary (MCS and PCS) scores. In the original study, outcome measures were administered at admission and 2 and 6 weeks, 3 and 6 months, and 1 and 2 years after injury; in the present extended follow-up study, the outcome measures were administered 5–10 years postinjury. Treatment comparison between patients in the TLSO group and those in the NO group was performed at the latest available follow-up, and the time-weighted average treatment effect was determined using a mixed-effects model of longitudinal regression for repeated measures averaged over all time periods. Missing data were assumed to be missing at random and were replaced with a set of plausible values derived using a multiple imputation procedure.RESULTSThe RMDQ score at 5–10 years postinjury was 3.6 ± 0.9 (mean ± SE) for the TLSO group and 4.8 ± 1.5 for the NO group (p = 0.486, 95% CI −2.3 to 4.8). Average kyphosis was 18.3° ± 2.2° for the TLSO group and 18.6° ± 3.8° for the NO group (p = 0.934, 95% CI −7.8 to 8.5). No differences were found between the NO and TLSO groups with time-weighted average treatment effects for RMDQ 1.9 (95% CI −1.5 to 5.2), for PCS −2.5 (95% CI −7.9 to 3.0), for MCS −1.2 (95% CI −6.7 to 4.2) and for average pain 0.9 (95% CI −0.5 to 2.2).CONCLUSIONSCompared with patients treated with a TLSO, patients treated using early mobilization without orthosis maintain similar pain relief and improvement in function for 5–10 years.

Download Full-text