scholarly journals Partial oral antibiotic treatment for bacterial brain abscess: an open-label randomized non-inferiority trial (ORAL)

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jacob Bodilsen ◽  
Matthijs C. Brouwer ◽  
Diederik van de Beek ◽  
Pierre Tattevin ◽  
Steven Tong ◽  
...  
Keyword(s):  
Brain Abscess ◽  
Antibiotic Treatment ◽  
Standard Treatment ◽  
Controlled Trial ◽  
Oral Treatment ◽  
Composite Endpoint ◽  
Primary Objective ◽  
Oral Antibiotic ◽  
Open Label ◽  
All Cause Mortality

Abstract Background The advised standard treatment for bacterial brain abscess following surgery is 6 to 8 weeks of intravenous (IV) antibiotic treatment, but an early switch to oral antibiotic treatment has been suggested to be equally effective. Methods This investigator-initiated, international, multi-center, parallel group, open-label, randomized (1:1 allocation) controlled trial will examine if oral treatment after 2 weeks of IV antibiotic therapy is non-inferior to standard 6–8 weeks of IV antibiotics for bacterial brain abscess in adults (≥ 18 years of age). The study will be conducted at hospitals across Denmark, the Netherlands, France, Australia, and Sweden. Exclusion criteria are severe immunocompromise or impaired gastro-intestinal absorption, pregnancy, device-related brain abscesses, and brain abscess caused by nocardia, tuberculosis, or Pseudomonas spp. The primary objective is a composite endpoint at 6 months after randomization consisting of all-cause mortality, intraventricular rupture of brain abscess, unplanned re-aspiration or excision of brain abscess, relapse, or recurrence. The primary endpoint will be adjudicated by an independent blinded endpoint committee. Secondary outcomes include extended Glasgow Outcome Scale scores and all-cause mortality at end of treatment as well as 3, 6, and 12 months since randomization, completion of assigned treatment, IV catheter associated complications, durations of admission and antibiotic treatment, severe adverse events, quality of life scores, and cognitive evaluations. The planned sample size is 450 patients for a one-sided alpha of 0.025 and a power of 90% to exclude a difference in favor of standard treatment of more than 10%. Date of initiation of first study center was November 3, 2020, with active recruitment for 3 years and follow-up for 1 year of all patients. Discussion The results of this study may guide future recommendations for treatment of bacterial brain abscess. If early transition to oral antibiotics proves non-inferior to standard IV treatment, this will provide considerable health and costs benefits. Trial registration ClinicalTrials.gov NCT04140903, first registered 28.10.2019. EudraCT number: 2019-002845-39, first registered 03.07.2019

scholarly journals Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ekaterina Alexeeva ◽  
Gerd Horneff ◽  
Tatyana Dvoryakovskaya ◽  
Rina Denisova ◽  
Irina Nikishina ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Controlled Trial ◽  
Randomized Study ◽  
Primary Objective ◽  
Disease State ◽  
Inactive Disease ◽  
Open Label ◽  
Standard Regimen ◽  
Double Blind ◽  
Early Combination Therapy

Abstract Background Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

scholarly journals Hemoglobin level at stabilization is associated with long-term all-cause mortality in patients with left-sided endocarditis, a POET substudy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Pries-Heje ◽  
R.B Hasselbalch ◽  
N Ihleman ◽  
S Gill ◽  
N.E Bruun ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Oral Treatment ◽  
Prosthetic Heart Valve ◽  
Hemoglobin Level ◽  
Common Finding ◽  
Funding Source ◽  
Long Term Outcome ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Background Left-sided infectious endocarditis (IE) has a high 1-year mortality. Anemia is a common finding in patients with IE, yet little is known about frequency, severity, and associated outcomes in this setting. Purpose To examine the relationship between Hemoglobin (Hgb) level measured at IE stabilization (time of randomization) in the Partial Oral versus intravenous Antibiotic Treatment of Endocarditis (POET) trial - and long-term all-cause mortality. Methods In the POET trial, 400 patients with left-sided IE were randomized, after medical and/or surgical stabilization, to conventional antibiotic treatment or partial oral treatment. Only non-surgically treated patients were considered in this study. Patients were divided by quartiles into four groups based on Hgb level at randomization. Results We examined 248 patients with non-surgically treated IE. Median time from diagnosis of IE to randomization was 14 days (IQ 12–19). At long-term follow-up (median 3.2 years, IQ 2.18–4.60), 71 patients had died (28.6%). Patients in the lowest quantile (Hgb ≤6.0 mmol) had a HR of 4.17 (95% CI 1.81–9.61, p<0.001) for death compared to patients in the highest quantile (Hgb >7.5 mmol/L). This association remained significant after multivariable adjustment for age, sex, renal disease, C-Reactive Protein, and Prosthetic heart valve (HR 2.69, 95% CI 1.11–6.50); p=0.028). Conclusion Low Hemoglobin level at stabilization in patients with IE was associated with an increased risk of long-term mortality. Whether intensified treatment of anemia in patients with IE could improve long-term outcome requires investigation. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Danish Heart Foundation, The Capital Regions Research Council

Severity of anaemia and association with all-cause mortality in patients with medically managed left-sided endocarditis

Heart ◽  
2021 ◽  
pp. heartjnl-2021-319637
Author(s):  
Mia Marie Pries-Heje ◽  
Rasmus Bo Hasselbalch ◽  
Christoffer Wiingaard ◽  
Emil Loldrup Fosbøl ◽  
Andreas Birkedal Glenthøj ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Mortality Rates ◽  
Severe Anaemia ◽  
Valve Surgery ◽  
Oral Antibiotic ◽  
Intravenous Antibiotic ◽  
All Cause Mortality ◽  
Mild Anaemia ◽  
Multivariable Adjustment

ObjectiveTo assess the prevalence and severity of anaemia in patients with left-sided infective endocarditis (IE) and association with mortality.MethodsIn the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial, 400 patients with IE were randomised to conventional or partial oral antibiotic treatment after stabilisation of infection, showing non-inferiority. Haemoglobin (Hgb) levels were measured at randomisation. Primary outcomes were all-cause mortality after 6 months and 3 years. Patients who underwent valve surgery were excluded due to competing reasons for anaemia.ResultsOut of 400 patients with IE, 248 (mean age 70.6 years (SD 11.1), 62 women (25.0%)) were medically managed; 37 (14.9%) patients had no anaemia, 139 (56.1%) had mild anaemia (Hgb <8.1 mmol/L in men and Hgb <7.5 mmol/L in women and Hgb ≥6.2 mmol/L) and 72 (29.0%) had moderate to severe anaemia (Hgb <6.2 mmol/L). Mortality rates in patients with no anaemia, mild anaemia and moderate to severe anaemia were 2.7%, 3.6% and 15.3% at 6-month follow-up and 13.5%, 20.1% and 34.7% at 3-year follow-up, respectively. Moderate to severe anaemia was associated with higher mortality after 6 months (HR 4.81, 95% CI 1.78 to 13.0, p=0.002) and after 3 years (HR 2.14, 95% CI 1.27 to 3.60, p=0.004) and remained significant after multivariable adjustment.ConclusionModerate to severe anaemia was present in 29% of patients with medically treated IE after stabilisation of infection and was independently associated with higher mortality within the following 3 years. Further investigations are warranted to determine whether intensified treatment of anaemia in patients with IE might improve outcome.

EORTC 1709/CCTG CE.8: A phase III trial of marizomib in combination with standard temozolomide-based radiochemotherapy versus standard temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2072-TPS2072 ◽  
Author(s):  
Patrick Roth ◽  
Jaap C. Reijneveld ◽  
Thierry Gorlia ◽  
Frederic Dhermain ◽  
Filip Yves Francine Leon De Vos ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Primary Objective ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Open Label ◽  
Phase Iii Trial ◽  
Newly Diagnosed Glioblastoma

TPS2072 Background: The standard treatment for patients with newly diagnosed glioblastoma comprises maximum safe surgery, radiotherapy (RT), and concomitant and up to six cycles of maintenance temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). Despite this intense therapy, the prognosis remains poor and there is an urgent need to develop new therapeutic options. Marizomib is a novel, irreversible and brain-penetrant pan-proteasome inhibitor. Following its successful assessment in phase I trials in patients with newly diagnosed as well as recurrent glioblastoma, marizomib is now being investigated in a phase III trial. Methods: EORTC 1709/CCTG CE.8 is a multicenter, randomized, controlled, open label phase III superiority trial. Eligibility criteria include histologically confirmed newly diagnosed glioblastoma and a performance status ≥70. Approximately a total of 750 patients will be enrolled and randomized 1:1. Stratification factors include institution, age, Karnofsky performance status and extent of surgery. The primary objective of this study is to compare overall survival in patients receiving marizomib in addition to standard of care (TMZ/RT→TMZ) with patients receiving standard treatment only. The testing strategy specifies the determination of this objective in both the intent-to-treat population and the subgroup of patients with tumors harboring an unmethylated MGMT promoter. Secondary endpoints include progression-free survival, safety, neurocognitive function and quality of life. The study is accompanied by a translational research program. The study will be opened at 50 EORTC sites in Europe and done as an intergroup collaboration with the Canadian Cancer Trials Group (CCTG) with 25 sites in Canada and additional sites in the US. Patient enrolment started in June 2018 and as of January 29, 2019, a total of 85 patients have been randomized. An update on the enrolment status will be provided at the ASCO conference. Clinical trial information: NCT03345095.

scholarly journals CASSETTE - clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation: study protocol for a randomised controlled trial

2019 ◽  
Author(s):  
Ravindra Dotel ◽  
Steven YC Tong ◽  
Asha Bowen ◽  
Jane N Nelson ◽  
Matthew VN O'Sullivan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pilot Study ◽  
Randomised Controlled Trial ◽  
Standard Treatment ◽  
Methicillin Resistance ◽  
Controlled Trial ◽  
Rate Of Change ◽  
Protein Synthesis Inhibitor ◽  
Open Label ◽  
Randomised Controlled

Abstract Background: Exotoxins are an important virulence factors in Staphylococcus aureus. Clindamycin, a protein synthesis inhibitor antibiotic, is thought to limit exotoxin production and improve outcomes in severe S. aureus infections. However, randomised prospective data to support this is lacking. Methods: An open label, multicenter, randomised controlled trial (RCT) will compare outcome differences in severe S. aureus infection between a standard treatment (flucloxacillin/cefazolin in methicillin-susceptible S. aureus; and vancomycin/daptomycin in methicillin-resistance S. aureus) and a standard treatment plus an additional clindamycin given for 7 days. We will include a minimum of 60 participants (both adult and children) in the pilot study. Participants will be enrolled within 72 hours of an index culture. Severe infections will include septic shock, necrotising pneumonia, or multifocal and non-contiguous skin and soft tissue/osteoarticular infections. Immunosuppressed, moribund, current severe diarrhea or C. difficile infection, pregnant, and those with anaphylaxis to beta-lactams or lincosamides will be excluded. Primary outcomes measure is number of days alive and free (1 or none) of SIRS (Systemic Inflammatory Response Syndrome) within the first 14 days post randomization. Secondary outcomes measure will include all-cause mortality at 14, 42 and 90 days, time to resolution of SIRS, proportion with microbiological treatment failure, and rate of change of C-reactive protein over time. Impacts of inducible clindamycin resistance, strains types, methicillin-susceptibility, and presence of various exotoxins will also be analysed. Discussion: This study will assess the effect of adjunctive clindamycin on patient-centered outcomes in severe, toxin mediated S. aureus infections. The Pilot study will provide feasibility for a much larger RCT. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001416381p. Registered 06 October 2017 Keywords: Staphylococcus aureus, exotoxins, prospective studies, clindamycin, leukocidins

scholarly journals Effect of dexamethasone in patients with ARDS and COVID-19 – prospective, multi-centre, open-label, parallel-group, randomised controlled trial (REMED trial): A structured summary of a study protocol for a randomised controlled trial

2021 ◽  
Author(s):  
Jan Maláska ◽  
Jan Stašek ◽  
František Duška ◽  
Martin Balík ◽  
Jan Máca ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Primary Objective ◽  
Efficacy And Safety ◽  
Open Label ◽  
Parallel Group ◽  
Secondary Objective ◽  
Randomised Controlled

Abstract ObjectivesThe primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days.

scholarly journals Safety and Efficacy of Ayurvedic Interventions and Yoga on Long Term Effects of COVID-19: a Structured Summary of a Study Protocol for a Randomized Controlled Trial

2021 ◽  
Author(s):  
Babita Yadav ◽  
Amit Rai ◽  
Pallavi Suresh Mundada ◽  
Richa Singhal ◽  
BCS Rao ◽  
...  
Keyword(s):  
Exploratory Study ◽  
Controlled Trial ◽  
Primary Objective ◽  
Self Management ◽  
Intervention Period ◽  
Long Term Effects ◽  
Open Label ◽  
Randomized Controlled ◽  
Parallel Group

Abstract Objectives: Primary Objective• To assess the efficacy of Ayurveda interventions and Yoga in rehabilitation of COVID-19 cases suffering with long term effects of COVID 19 as compared to WHO Rehabilitation Self-Management after COVID-19- Related Illness.Secondary Objective• To assess the safety of Ayurvedic interventions in cases suffering with long term effects of COVID 19Trial design: Multi-centric, randomized, controlled, parallel group, open-label, exploratory study. The study duration is 9 months and the intervention period is 90 days from the day of enrolment of the participant.

scholarly journals An open-label, parallel-group, randomised controlled trial of antiseptic mouthwash versus antibiotics for oropharyngeal gonorrhoea treatment (OMEGA2)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eric P. F. Chow ◽  
Kate Maddaford ◽  
Jane S. Hocking ◽  
Catriona S. Bradshaw ◽  
Rebecca Wigan ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Standard Treatment ◽  
Controlled Trial ◽  
Health Centre ◽  
Nucleic Acid Amplification ◽  
Open Label ◽  
Parallel Group ◽  
Randomised Controlled ◽  
New Treatments ◽  
Clinical Trials Registry

Abstract New treatments for oropharyngeal gonorrhoea are required to address rising antimicrobial resistance. We aimed to examine the efficacy of a 14-day course of mouthwash twice daily compared to standard treatment (antibiotic) for the treatment of oropharyngeal gonorrhoea. The OMEGA2 trial was a parallel-group and open-labelled randomised controlled trial among men with untreated oropharyngeal gonorrhoea that was conducted between September 2018 and February 2020 at Melbourne Sexual Health Centre in Australia. Men were randomised to the intervention (rinsing, gargling and spraying mouthwash twice daily for 14 days) or control (standard treatment) arm and followed for 28 days. Participants in both arms were advised to abstain from sex and kissing with anyone for 14 days after enrolment. Oropharyngeal swabs were collected at baseline, Day 14 and Day 28 and tested for Neisseria gonorrhoeae by nucleic acid amplification test (NAAT) and culture. The primary outcome was the detection of oropharyngeal N. gonorrhoeae by NAAT at Day 14 after treatment. This trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12618001380280). This trial stopped early due to a high failure rate in the mouthwash arm. Twelve men were randomly assigned to either mouthwash (n = 6) or standard treatment (n = 6). Of the 11 men who returned at Day 14, the cure rate for oropharyngeal gonorrhoea in the mouthwash arm was 20% (95% CI 1–72%; 1/5) and in the standard treatment arm was 100% (95% CI 54–100%; 6/6). A 14-day course of mouthwash failed to cure a high proportion of oropharyngeal gonorrhoea cases.

Direct Renin Inhibition in Non-diabetic chronic Kidney disease (DRINK): a prospective randomized trial

2020 ◽  
Author(s):  
Sydney C W Tang ◽  
Kam Wa Chan ◽  
Dennis K M Ip ◽  
Desmond Y H Yap ◽  
Maggie K M Ma ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Controlled Trial ◽  
Composite Endpoint ◽  
Rate Of Change ◽  
Control Group ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Open Label ◽  
Baseline Serum

Abstract Background The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients. Methods In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3–4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone. Primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Secondary endpoints included rate of change in urine protein-to-creatinine ratio (UPCR), cardiovascular events and hyperkalemia. Composite renal outcomes of doubling of baseline serum creatinine or a 40% reduction in eGFR or incident end-stage renal disease or death were analyzed as post hoc analysis. Results Seventy-six patients were randomized: 37 to aliskiren (mean age 55.1 ± 11.1 years) and 39 to control (mean age 55.0 ± 9.4 years). Their baseline demographics were comparable to eGFR (31.9 ± 9.0 versus 27.7 ± 9.0 mL/min/1.73 m2, P = 0.05) and UPCR (30.7 ± 12.6 versus 47.8 ± 2.8 mg/mmol, P = 0.33) for treatment versus control subjects. After 144 weeks of follow-up, there was no difference in the rate of eGFR change between groups. Six patients in the aliskiren group and seven in the control group reached the renal composite endpoint (16.2% versus 17.9%, P = 0.84). The cardiovascular event rate was 10.8% versus 2.6% (P = 0.217). The hyperkalemia rate was 18.9% versus 5.1% with an adjusted hazard ratio of 7.71 (95% confidence interval 1.14 to 52.3, P = 0.04) for the aliskiren arm. Conclusion Aliskiren neither conferred additional renoprotective benefit nor increased adverse events, except for more hyperkalemia in nondiabetic CKD patients.

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