630. Emergence of Colistin Resistance in the OVERCOME Trial: Impact of Combination Therapy with Meropenem

Abstract Background Colistin (COL) remains an important therapeutic option for carbapenem-resistant (CR) Gram-negative bacilli (GNB). COL is often utilized in combination with meropenem (MEM), in part due to concerns regarding the development of COL resistance with monotherapy. We recently completed a randomized controlled trial comparing outcomes in patients receiving COL + placebo to those receiving COL + MEM; herein we present data on the emergence of COL resistance in this trial. Methods OVERCOME was an international, multicenter, randomized, double-blind, placebo-controlled study comparing COL and COL + MEM for the treatment of bloodstream infection and/or pneumonia due to CR GNB. Subjects were included in the modified intent to treat population (mITT) if their enrollment pathogen had a COL MIC ≤2 mg/L, as determined by broth microdilution (BMD). Daily blood and/or respiratory samples were obtained in patients per protocol until two consecutive negatives were obtained or the end of study treatment. All subsequent isolates were evaluated for COL resistance via BMD, defined as MIC ≥ 4 mg/L. Results Of the 425 patients in the mITT population, 380 (191 COL; 189 COL + MEM) were evaluable for the endpoint of COL resistance development. The median age of the cohort was 70, 38% were female, 47% were white, and 45% were Asian. 70% had an index infection of pneumonia, 68% were in the intensive care unit at the onset of their infection, and A. baumannii was the most common pathogen (78% of patients). Baseline characteristics, infection type, severity of illness, and index pathogen were similar amongst treatment arms. No significant difference in resistance development was seen between the COL and COL + MEM groups overall (12% vs. 8%; p = 0.31), or in any subgroup (Table). In patients with A. baumannii, there was a trend towards decreased resistance development with COL + MEM (13.3% vs 7.5%; p = 0.13). Conclusion We were unable to identify a significant difference in resistance emergence between treatment arms, but given the low incidence of this outcome, were underpowered to do so. The impact of COL + MEM on preventing emergence of COL resistance in A. baumannii warrants further clinical study. Disclosures Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support) Emmanuel Roilides, MD, PhD, FIDSA, FAAM, FESCMID, Merck Sharp & Dohme Corp. (Consultant, Grant/Research Support) Matthew Sims, MD, PhD, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor)

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Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study

Gut ◽

10.1136/gutjnl-2018-316434 ◽

2018 ◽

Vol 67 (12) ◽

pp. 2107-2115 ◽

Cited By ~ 96

Author(s):

Sofie Ingdam Halkjær ◽

Alice Højer Christensen ◽

Bobby Zhao Sheng Lo ◽

Patrick Denis Browne ◽

Stig Günther ◽

...

Keyword(s):

Gut Microbiota ◽

Controlled Trial ◽

Symptom Relief ◽

Controlled Study ◽

Faecal Microbiota ◽

Double Blind ◽

Double Blind Placebo ◽

Faecal Microbiota Transplantation ◽

Faecal Samples ◽

Significant Difference

ObjectiveIBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS.DesignWe performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected.ResultsA significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not.ConclusionIn this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS.Trial registration numberNCT02788071.

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Dexamethasone (DM) for cancer-related fatigue: A double-blinded, randomized, placebo-controlled trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.9002 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 9002-9002 ◽

Cited By ~ 6

Author(s):

Sriram Yennurajalingam ◽

Susan Frisbee-Hume ◽

Marvin Omar Delgado-Guay ◽

Janet Bull ◽

Alexandria T. Phan ◽

...

Keyword(s):

Advanced Cancer ◽

Controlled Trial ◽

Symptom Assessment ◽

Primary Objective ◽

Controlled Study ◽

Advanced Cancer Patients ◽

Double Blind ◽

Cancer Related Fatigue ◽

Significant Difference ◽

Edmonton Symptom Assessment Scale

9002 Background: Cancer-related-fatigue (CRF) is the most common and distressing symptoms in patients with advanced cancer. Currently, there is no standard treatment for CRF. Although corticosteroids have been used in the treatment of CRF, there are no well-powered placebo-controlled trials that used a validated CRF outcome measure. The primary objective of this prospective, randomized, double-blind, placebo-controlled study is to compare the effect of DM versus placebo on CRF. Methods: Advanced cancer patients with fatigue ≥ 4/10 on the Edmonton Symptom Assessment Scale (ESAS) and at least 2 other CRF-related symptoms (pain, nausea, appetite, depression, anxiety or sleep disturbance ≥ 4/10), normal cognition, no infections and hemoglobin ≥ 9 g/L were eligible for enrollment. Patients were randomized to either receive dexamethasone 4 mg orally twice a day for 15 days (primary end point) or matching placebo. The primary outcome was the day 15 change in Functional Assessment of Chronic Illness-Fatigue (FACIT-F) subscale scores. Differences in the group means (normal distribution) were analyzed using the two-sample t-test. Results: In 83 evaluable patients (43 DM and 40 placebo), median age was 60 years, 61% were white, and 53% were female. There was no difference in the demographics and fatigue (FACIT-F subscale) between DM and placebo groups except for sex (p=0.02). The mean (SD) FACIT-F subscores at baseline and at day 15 for DM were 18 (11) and 27 (11) (p<0.001) and for placebo were 21 (9) and 24 (12) (p=0.06), respectively. Mean improvement in FACIT-F subscale was significantly higher in the DM group compared to placebo (9.6 (11) vs. 3.1 (9.7), p=0.005). We found a significant difference in ESAS physical distress (p=0.02), but no differences in ESAS overall symptom distress (p=0.11) and ESAS psychological distress (P=0.88) between DM and placebo. There were insignificantly higher numbers of grade ≥3 toxicities in patients who received DM than in patients who received placebo (20/42 vs. 18/47, p=0.37). Conclusions: Dexamethasone was more effective than placebo in reducing CRF in patients with advanced cancer. Long-term safety studies are needed.

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Periarticular Injection with Bupivacaine for Postoperative Pain Control in Total Knee Replacement: A Prospective Randomized Double-Blind Controlled Trial

Advances in Orthopedics ◽

10.1155/2012/107309 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 19

Author(s):

Varah Yuenyongviwat ◽

Chaturong Pornrattanamaneewong ◽

Thitima Chinachoti ◽

Keerati Chareancholvanich

Keyword(s):

Pain Control ◽

Controlled Trial ◽

Ease Of Use ◽

Morphine Consumption ◽

Controlled Study ◽

Control Group ◽

Double Blind ◽

Periarticular Injection ◽

Post Operative Pain ◽

Significant Difference

Background. Local periarticular injection with bupivacaine alone in TKA has not been studied. Thus, we aimed to examine the effectiveness of local periarticular injection with bupivacaine for post-operative pain control in TKA.Method. Sixty patients undergoing TKA by a single surgeon were randomly assigned into two groups in a double-blind, placebo-controlled study. In the injection group, patients received periarticular injections with 0.25% bupivacaine before wound closure; in the control group, patients received a 0.9% normal saline injection. Both groups received the same anesthetic procedure, post-operative pain control, and rehabilitation protocol.Results. There was a significant reduction in post-operative morphine consumption in the first six hours after the operation (mean 0.9 mg and 2.43 mg,P=0.01), but there was no significant difference in post-operative morphine consumption between six hours and ninety-six hours after the operation, visual analogue scale (VAS) score, morphine side effects during the first 96 hours, length of hospital stay, or complications from morphine consumption.Conclusion. Local periarticular injection with bupivacaine alone before wound closer was shown to be an effective method to improve pain control after TKA with a few complications and ease of use.

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Probiotics with vitamin C for the prevention of upper respiratory tract symptoms in children aged 3-10 years: randomised controlled trial

Beneficial Microbes ◽

10.3920/bm2020.0185 ◽

2021 ◽

pp. 1-10

Author(s):

I. Garaiova ◽

Z. Paduchová ◽

Z. Nagyová ◽

D. Wang ◽

D.R. Michael ◽

...

Keyword(s):

Vitamin C ◽

Respiratory Tract ◽

Controlled Trial ◽

Bifidobacterium Bifidum ◽

Active Group ◽

Controlled Study ◽

Upper Respiratory Tract ◽

Double Blind ◽

Upper Respiratory ◽

The Impact

In a double-blind, randomised, parallel-group, placebo-controlled study, healthy school children aged 3-10 years received a probiotic based supplement daily for 6 months to assess the impact on the incidence and duration of upper respiratory tract infection (URTI) symptoms. The intervention comprised Lab4 probiotic (Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) at 12.5 billion cfu/day plus 50 mg vitamin C or a matching placebo. 171 children were included in the analysis (85 in placebo and 86 in active group). Incidence of coughing was 16% (P=0.0300) significantly lower in the children receiving the active intervention compared to the placebo. No significant differences in the incidence rate of other URTI symptoms were observed. There was significantly lower risk of experiencing five different URTI related symptoms in one day favouring the active group (Risk ratio: 0.31, 95% confidence interval: 0.12, 0.81, P=0.0163). Absenteeism from school and the use of antibiotics was also significantly reduced for those in the active group (-16%, P=0.0060 and -27%, P=0.0203, respectively). Our findings indicate that six months daily supplementation with the Lab4 probiotic and vitamin C combination reduces the incidence of coughing, absenteeism and antibiotic usage in 3 to 10 year old children.

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Donepezil for cancer-related fatigue: A double-blind, randomized, placebo-controlled study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.9003 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 9003-9003

Author(s):

E. Bruera ◽

B. El Osta ◽

V. Valero ◽

L. Driver ◽

J. Palmer ◽

...

Keyword(s):

Advanced Cancer ◽

Controlled Trial ◽

Subscale Score ◽

Assessment System ◽

Phone Call ◽

Controlled Study ◽

Fatigue Improvement ◽

Open Label ◽

Double Blind ◽

Significant Difference

9003 Background: Fatigue is the most frequent symptom in advanced cancer. No standard treatment is available. We previously found that open-label donepezil significantly improved fatigue by day 3 and 7 in patients (pts) on opioids for cancer pain (Fisch et al, ASCO 2003). The purpose of this study was to compare donepezil (D) with placebo (P) for fatigue in pts with advanced cancer. Methods: In this randomized, double-blind, placebo-controlled trial, pts with fatigue score = 4 on a 0 to 10 scale (10 = worst fatigue) for > 1 week, hemoglobin = 10g/dl for = 4 weeks, and no major contraindication to D were randomized to receive D 5 mg or P orally every morning for 7 days. All pts were offered open-label D during week 2. Assessment included: research nurse daily phone call for fatigue and toxicity evaluation, Edmonton Symptom Assessment System (ESAS), Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F), Sleeping Pattern Assessment, and overall effectiveness of the treatment. The FACIT-F fatigue subscale score on day 8 was considered the primary endpoint. Results: 103 pts were evaluable for final analysis. Mean difference in scores for symptoms intensity between baseline and day 8 are shown in Table 1 . FACIT-F fatigue subscale score at day 8 decreased a mean of 6 (10.6 SD) in the D arm (p < 0.001) and 7.2 (9.5 SD) in the P arm (p < 0.001). There was no significant difference in fatigue improvement between both arms according to the FACIT-F subscale (p = 0.57) and ESAS fatigue (p = 0.18) scores, and no significant difference in sleep quality score between D and P. On day 15 of the open-label phase, mean fatigue intensity remained significantly improved as compared to baseline on FACIT-F fatigue subscale (p < 0.001) and ESAS fatigue (p < 0.001) scores. No significant toxicities were observed. Conclusions: Both donepezil and placebo resulted in significant fatigue improvement. Donepezil was not significantly superior to placebo after one week. Our pilot findings are probably due to placebo effect. No significant financial relationships to disclose. [Table: see text]

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CONTROLLED STUDY OF LINEAR GROWTH IN ASTHMATIC CHILDREN DURING TREATMENT WITH INHALED GLUCOCORTICOSTEROIDS

PEDIATRICS ◽

10.1542/peds.94.2.270a ◽

1994 ◽

Vol 94 (2) ◽

pp. 270-270

Author(s):

Christopher Randolph

Keyword(s):

School Children ◽

Growth Velocity ◽

Linear Growth ◽

Lower Leg ◽

Mild Asthma ◽

Controlled Study ◽

Double Blind ◽

Significant Difference ◽

Inhaled Budesonide ◽

The Impact

Purpose of the Study. To determine the impact of short term inhaled budesonide on linear growth in school children with mild asthma. Study Population. Forty-three school children with mild asthma. Methods. A randomized double blind parallel group study with three dose groups of 200, 400, and 800 µg of budesonide per day administered with a 750-mL spacer (Nebuhaler). Each group received budesonide for 8 consecutive weeks. Placebo was given 4 weeks before or after budesonide. Findings. Compared with placebo, children treated with 800 µg of budesonide had a statistically significant lower leg growth velocity by 0.26 mm/week (P < .0012; t = 5.0; df = 11; 95% confidence interval, 0.14 to 0.37 mm/week). There was no statistically significant difference in the growth velocity between 200 or 400 µg of budesonide treatments and placebo. Reviewer's Comments. This study was conducted with knemometry, a method utilized in measuring the length of the lower leg with apparent high reproducibility and accuracy. Unfortunately, the correlation between growth of the lower leg and chronic growth is undear. Several steroid studies in the past have indicated that budesonide up to levels of 800 µg does not interfere with long term growth. Thus, the impact of the study is unclear at present. Clearly, a longer term study is necessary to determine the outcome of these children. Additionally, it would be important to see the impact of budesonide in chronic asthma with greater severity, which itself may interfere with growth.

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Achieving remission in psoriatic arthritis by early initiation of TNF inhibition: a double-blind, randomised, placebo-controlled trial of golimumab plus methotrexate versus placebo plus methotrexate

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214746 ◽

2019 ◽

Vol 78 (5) ◽

pp. 610-616 ◽

Cited By ~ 7

Author(s):

Leonieke J J van Mens ◽

Henriëtte M de Jong ◽

Inka Fluri ◽

Michael T Nurmohamed ◽

Marleen G H van de Sande ◽

...

Keyword(s):

Adverse Event ◽

Psoriatic Arthritis ◽

Controlled Trial ◽

Early Initiation ◽

Controlled Study ◽

Tender Joint Count ◽

Tender Joint ◽

Double Blind ◽

Significant Difference ◽

Patient Reported

ObjectivesEarly initiation of effective treatment favours remission in rheumatoid arthritis, but it remains unknown if the same concept applies to psoriatic arthritis (PsA). Therefore, this study investigated whether the combination of golimumab plus methotrexate (MTX) as a first-line treatment is superior to MTX alone in inducing remission in PsA.MethodsThis investigator-initiated, multicentre, double-blind, randomised, placebo-controlled trial included 51 MTX and bDMARD-naive patients with PsA fulfilling the CASPAR criteria and with active disease at baseline (≥3 swollen joint count/tender joint count). Patients were randomised to golimumab (50 mg SC monthly)+MTX (n=26) (TNFi arm) or matched placebo+MTX (n=25) (MTX arm). MTX was started 15 mg/week and increased to 25 mg/week over 8 weeks. The primary endpoint was percentage of patients achieving Disease Activity Score (DAS) remission (<1.6) at week 22. Safety was assessed throughout the study.ResultsThe primary efficacy endpoint was achieved by 81% in the TNFi arm versus 42 % in the MTX arm (p=0.004). This difference in DAS remission was already observed at week 8. A significant difference in favour of the golimumab+MTX arm at week 22 was also observed for other response criteria such as MDA, ACR20/50/70, disease measures and patient-reported outcomes. The occurrence rates of adverse event and treatment-emergent adverse event were similar in both arms.ConclusionsIn patients with early PsA, DAS remission at week 22 was almost doubled with golimumab+MTX versus MTX alone. This double-blind, randomised, placebo-controlled study supports the concept that early initiation of TNFi in patients with PsA favours remission.Trial registration numberNCT01871649.

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Double-blind placebo-controlled trial of etanercept in the prevention of work disability in ankylosing spondylitis: Table 1

Annals of the Rheumatic Diseases ◽

10.1136/ard.2009.121327 ◽

2010 ◽

Vol 69 (11) ◽

pp. 1926-1928 ◽

Cited By ~ 46

Author(s):

Nick Barkham ◽

Laura C Coates ◽

Helen Keen ◽

Elizabeth Hensor ◽

Alexander Fraser ◽

...

Keyword(s):

Placebo Group ◽

Ankylosing Spondylitis ◽

Clinical Outcomes ◽

Job Loss ◽

Controlled Trial ◽

Controlled Study ◽

Double Blind ◽

Treatment Groups ◽

Gait Parameters ◽

Significant Difference

ObjectivesEtanercept has been shown to be rapidly effective in suppressing disease activity in ankylosing spondylitis (AS). The aim of this study was to determine whether etanercept improves work instability as measured by the Ankylosing Spondylitis Work Instability Scale (AS-WIS).MethodForty patients with active AS who were in work but were work unstable were recruited. Patients were randomised to receive 25 mg etanercept or placebo twice weekly for 12 weeks. The primary outcome was change in AS-WIS at week 12. The AS-WIS is a patient-derived outcome measure which allows stratification of the risk of job loss. Secondary outcomes included clinical outcomes and gait parameters.ResultsThe mean improvement in AS-WIS score at week 12 was 2.75 in the etanercept group and 0.68 in the placebo group (p=0.125). The risk of job loss decreased for 11 (55%) of the etanercept group compared with 7 (35%) in the placebo group. Conversely, the risk of job loss increased in 3 (15%) of the placebo group compared with 1 (5%) in the etanercept group. There was no statistically significant difference between treatment groups in change in WIS categories (Mann–Whitney U test=0.153, p=0.160). Significant improvement with etanercept was seen at week 12 in clinical outcomes and gait parameters. Etanercept was well tolerated, with no dropouts due to adverse events.ConclusionThis small study confirms the efficacy of etanercept on clinical outcome measures in patients with AS and suggests an effect on work instability which needs to be replicated in a larger controlled study.

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The use of Prophylactic Flucloxacillin in Treatment of Open Fractures of the Distal Phalanx within an Accident and Emergency Department: A Double-Blind Randomized Placebo-Controlled Trial

Journal of Hand Surgery (European Volume) ◽

10.1016/s0266-7681(03)00175-x ◽

2003 ◽

Vol 28 (5) ◽

pp. 388-394 ◽

Cited By ~ 39

Author(s):

J. STEVENSON ◽

G. MCNAUGHTON ◽

J. RILEY

Keyword(s):

Emergency Department ◽

Open Fracture ◽

Controlled Trial ◽

Distal Phalanx ◽

Open Fractures ◽

Controlled Study ◽

Double Blind ◽

Accident And Emergency ◽

Significant Difference ◽

Accident And Emergency Department

Open fractures of the distal phalanx commonly present to the Accident and Emergency Department. Controversy surrounds the use of prophylactic antibiotics in treating this injury. A double-blind, prospective, randomized placebo-controlled study was undertaken comparing the use of prophylactic flucloxacillin to placebo in addition to meticulous wound toilet. One hundred and ninety-three adult patients with an open fracture of the distal phalanx were studied. Seven patients developed superficial infections, an overall infection rate of 4%. No patient developed osteitis or a deep wound infection. There were three cases of infection in the 98 patients (3%) in the antibiotic group and four cases of infection in the 95 patients (4%) in the placebo group. A difference of proportion test confirmed no significant difference. It is concluded that the addition of prophylactic flucloxacillin to thorough wound toilet and careful soft-tissue repair of open fracture of the distal phalanx confers no benefit.

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Effect of Recombinant Human Parathyroid Hormone (1-84) on Resolution of Active Charcot Neuro-osteoarthropathy in Diabetes: A Randomized, Double-Blind, Placebo-Controlled Study

10.2337/figshare.14473611.v1 ◽

2021 ◽

Author(s):

Nina L Petrova ◽

Nicholas K. Donaldson ◽

Maureen Bates ◽

Wegin Tang ◽

Timothy Jemmott ◽

...

Keyword(s):

Parathyroid Hormone ◽

Controlled Trial ◽

Linear Regression Analysis ◽

Controlled Study ◽

X Rays ◽

Human Parathyroid Hormone ◽

Double Blind ◽

Double Blind Placebo ◽

Significant Difference ◽

Prolonged Immobilization

Objectives: Fractures in Charcot neuro-osteoarthropathy (CN) often fail to heal despite prolonged immobilization with below-knee casting. The aim of the study was to assess the efficacy of recombinant human parathyroid hormone (PTH) in reducing time to resolution of CN and healing of fractures. Research Design and Methods: People with diabetes and acute (active) Charcot foot were randomized (double-blind) to either full length PTH (1-84) or placebo therapy - both in addition to below-knee casting and Calcium and Vitamin D3 supplementation. The primary outcome was resolution of CN, defined as a skin foot temperature difference below 2°C at two consecutive monthly visits. Results: Median time to resolution was 5 months (95% CI 4, 12) in intervention and 6 months (95% CI 2, 9) in control. There was no significant difference in time to resolution between the groups (mixed effects logistic regression; p=0.64). The hazard ratio of resolution was 0.84 (95% CI 0.41, 1.74), p=0.64 and the odds ratio of resolution by 12 months was 1.22 (0.90, 1.67), p=0.20 (intervention versus control). On linear regression analysis, there were no significant differences in the effect of treatment on fracture scores quantitated on magnetic resonance imaging <a>scans </a>(coef= 0.13; 95% CI -0.62, 0.88; p=0.73) and on foot and ankle X-rays (coef= 0.30; 95% CI -0.03, 0.63; p=0.07). Conclusions: This double-blind placebo-controlled trial did not reduce time to resolution or enhance fracture healing of CN. There was no added benefit of daily intervention with PTH (1-84) to below-knee casting in achieving earlier resolution of CN.

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