scholarly journals Study protocol for a randomised trial for atosiban versus placebo in threatened preterm birth: the APOSTEL 8 study

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e029101 ◽  
Author(s):  
Job Klumper ◽  
Wouter Breebaart ◽  
Carolien Roos ◽  
Christiana A Naaktgeboren ◽  
Joris van der Post ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Neonatal Outcome ◽  
Randomised Trial ◽  
Neonatal Morbidity ◽  
Cervical Length ◽  
Controlled Clinical Trial ◽  
Intention To Treat ◽  
Registration Number ◽  
The Uk ◽  
Double Blinded

IntroductionPreterm birth complicates >15 million pregnancies annually worldwide. In many countries, women who present with signs of preterm labour are treated with tocolytics for 48 hours. Although this delays birth, it has never been shown to improve neonatal outcome. In 2015, the WHO stated that the use of tocolytics should be reconsidered and that large placebo-controlled studies to evaluate the effectiveness of tocolytics are urgently needed.Methods and analysisWe designed an international, multicentre, randomised, double-blinded, placebo-controlled clinical trial. Women with threatened preterm birth (gestational age 30–34 weeks), defined as uterine contractions with (1) a cervical length of < 15 mm or (2) a cervical length of 15–30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or insulin-like growth factor binding protein-1 (Actim-Partus test) or (4) ruptured membranes, will be randomly allocated to treatment with atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Analysis will be by intention to treat. A sample size of 1514 participants (757 per group) will detect a reduction in adverse neonatal outcome from 10% to 6% (alpha 0.05, beta 0.2). A cost-effectiveness analysis will be performed from a societal perspective.Ethics and disseminationThis study has been approved by the Research Ethics Committee (REC) of the Amsterdam University Medical Centres, location AMC, as well as the REC’s in Dublin and the UK. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results.Trial registration numberNederlands Trial Register (Trial NL6469).

scholarly journals Cast versus functional brace in the rehabilitation of patients treated for an ankle fracture: protocol for the UK study of ankle injury rehabilitation (AIR) multicentre randomised trial

BMJ Open ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. e027242 ◽  
Author(s):  
Rebecca Samantha Kearney ◽  
Rebecca McKeown ◽  
Siobhan Stevens ◽  
Nicholas Parsons ◽  
Helen Parsons ◽  
...  
Keyword(s):  
Ankle Fracture ◽  
Primary Outcome ◽  
Randomised Trial ◽  
Operative Management ◽  
Plaster Cast ◽  
Reference Case ◽  
Intention To Treat ◽  
Functional Brace ◽  
Registration Number ◽  
The Uk

IntroductionEach year in the UK over 120 000 people fracture their ankle. It is not known what the best rehabilitation strategy is for these people. Traditionally standard care has involved immobilisation in a plaster cast but an alternative is a functional brace, which can be removed to allow early movement. This paper details the protocol for a multicentre randomised trial of plaster cast immobilisation versus functional bracing for patients with an ankle fracture.Methods and analysisWe will recruit adults with a fractured ankle, for which the treating clinician would consider plaster cast to be a reasonable management option. Randomisation will be on a 1:1 basis, stratified by centre, operative or non-operative management and age. Participants will be allocated to either plaster cast or a functional brace, both treatments are widely used. To have 90% power to detect a difference of 10 points on the primary outcome (Olerud and Molander Ankle Score) at the primary outcome time point (16 weeks), we need to randomise a minimum of 478 people. Quality of life and resource use will be collected at 6, 10, 16, 24 weeks and 12, 18, 24 months. The differences between treatment groups will be assessed on an intention-to-treat basis. The economic evaluation will adhere to the recommendations of the National Institute for Health and Care Excellence reference case.Ethics, registration and disseminationNational Research Ethic Committee approved this study on 4 July 2017 (17/WM/0239). The first site opened to recruitment 9 October 2017. The results of this trial will be submitted to a peer-reviewed journal and will inform clinical practice.Trial registration numberISRCTN15537280; Pre-results.

scholarly journals Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040110
Author(s):  
Mikaela Smit ◽  
Annalisa Marinosci ◽  
Giovanni Jacopo Nicoletti ◽  
Thomas Perneger ◽  
Silvio Ragozzino ◽  
...  
Keyword(s):  
Randomised Trial ◽  
Standard Of Care ◽  
Cluster Randomised Trial ◽  
Postexposure Prophylaxis ◽  
Open Label ◽  
Daily Monitoring ◽  
Intention To Treat ◽  
Cluster Randomised ◽  
Registration Number ◽  
Asymptomatic Individuals

IntroductionLopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2.Methods and analysisCOPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total.Ethics and disseminationEthics approval has been granted by the Commission Cantonale d’Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences.Trial registration numberClinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732).Registered report identifierCCER 2020-0864.

Fetal Fibronectin, Endotoxin, Bacterial Vaginosis and Cervical Length as Predictors of Preterm Birth and Neonatal Morbidity in Twin Pregnancies

1998 ◽  
Vol 53 (7) ◽  
pp. 402-403
Author(s):  
U.-B. Wennerholm ◽  
B. Holm ◽  
I. Mattsby-Baltzer ◽  
T. Nielsen ◽  
J. Platz-Christensen ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Bacterial Vaginosis ◽  
Neonatal Morbidity ◽  
Cervical Length ◽  
Fetal Fibronectin ◽  
Twin Pregnancies

scholarly journals Double-blinded randomised placebo-controlled clinical trial of individualised homeopathic treatment of hyperthyroid cats

2017 ◽  
Vol 180 (15) ◽  
pp. 377-377 ◽  
Author(s):  
A. L. Bodey ◽  
C. J. Almond ◽  
M. A. Holmes
Keyword(s):  
Randomised Trial ◽  
Case Definition ◽  
Controlled Clinical Trial ◽  
Second Phase ◽  
P Values ◽  
Endocrine Disorder ◽  
Homeopathic Treatment ◽  
Before And After ◽  
Definition Of ◽  
Double Blinded

Feline hyperthyroidism is a common endocrine disorder in older cats for which homeopathic treatment has been advocated. A double-blinded, placebo-controlled randomised trial was performed to look for evidence of efficacy for the use of individualised homeopathy in the treatment of this disease. Using a case definition of a concentration of the thyroid hormone T4 >66 nmol/l, cats were randomised into two treatment arms. Either a placebo or a homeopathic treatment was given to each cat blindly. After 21 days, the T4 levels, weight (Wt) and heart rate (HR) were compared with pretreatment values. There were no statistically significant differences in the changes seen between the two treatment arms following placebo or homeopathic treatment (T4 P=0.96, Wt P=0.16, HR P=0.36) or between the means of each parameter for either treatment arm before and after placebo or homeopathic treatment (all P values >0.13). In a second phase of the study, patients in both treatment arms were given methimazole treatment for 21 days and T4, Wt and HR determined again. Again there were no statistically significant differences between the groups, but there were statistically significant reductions in T4 (P<0.0001) and HR (P=0.02), and a statistically significant increase in Wt (P=0.004) in both groups compared with their pre-methimazole treatment levels. The results of this study failed to provide any evidence of the efficacy of homeopathic treatment of feline hyperthyroidism.

scholarly journals Diagnostic Potential of Evaluation of SDF-1αand sRAGE Levels in Threatened Premature Labor

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Rafał Rzepka ◽  
Barbara Dołęgowska ◽  
Aleksandra Rajewska ◽  
Daria Sałata ◽  
Marta Budkowska ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Latency Period ◽  
Neonatal Morbidity ◽  
Diagnostic Value ◽  
Cervical Length ◽  
Ultrasound Measurement ◽  
Premature Labor ◽  
Diagnostic Potential ◽  
Group A ◽  
Group B

Preterm birth remains the most prevalent cause of neonatal morbidity. This study aimed to evaluate the diagnostic value of SDF-1α, resistin, secretory RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) in preterm labor. A total of 211 pregnant women participated in the study. Group A contained 72 women between 22 and 36 weeks of gestation, with premature labor, who finally had preterm birth. Group B contained 66 women in labor between 37 and 41 weeks of gestation. Women in group A had lower SDF-1αand sRAGE levels than those in group B. Moreover, in group A, SDF-1αand sRAGE levels were correlated with the latency period from the occurrence of premature labor symptoms until delivery. Sensitivity and specificity of studied parameters for prediction of preterm birth were 95% and 40% for SDF-1αand 51.3% and 93.5% for sRAGE, respectively. The prognostic value of plasma SDF-1αand sRAGE levels was comparable with that of cervical length ultrasound measurement and serum C-reactive protein levels. We conclude that SDF-1αand sRAGE appear to play a major role in the diagnosis of preterm birth and its evaluation could be convenient and useful for predicting preterm birth.

scholarly journals Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001455 ◽  
Author(s):  
Maria Isabel Lopes ◽  
Leticia P Bonjorno ◽  
Marcela C Giannini ◽  
Natalia B Amaral ◽  
Pamella Indira Menezes ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Placebo Group ◽  
Standard Treatment ◽  
Supplemental Oxygen ◽  
Controlled Clinical Trial ◽  
Beneficial Effects ◽  
Primary Endpoints ◽  
Registration Number ◽  
Double Blinded ◽  
Supplemental Oxygen Therapy

ObjectiveTo evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes.DesignWe present the results of a randomised, double-blinded, placebo-controlled clinical trial of colchicine for the treatment of moderate to severe COVID-19, with 75 patients allocated 1:1 from 11 April to 30 August 2020. Colchicine regimen was 0.5 mg thrice daily for 5 days, then 0.5 mg twice daily for 5 days. The primary endpoints were the need for supplemental oxygen, time of hospitalisation, need for admission and length of stay in intensive care unit and death rate.ResultsSeventy-two patients (36 for placebo and 36 for colchicine) completed the study. Median (and IQR) time of need for supplemental oxygen was 4.0 (2.0–6.0) days for the colchicine group and 6.5 (4.0–9.0) days for the placebo group (p<0.001). Median (IQR) time of hospitalisation was 7.0 (5.0–9.0) days for the colchicine group and 9.0 (7.0–12.0) days for the placebo group (p=0.003). At day 2, 67% versus 86% of patients maintained the need for supplemental oxygen, while at day 7, the values were 9% versus 42%, in the colchicine and the placebo groups, respectively (log rank; p=0.001). Two patients died, both in placebo group. Diarrhoea was more frequent in the colchicine group (p=0.26).ConclusionColchicine reduced the length of both, supplemental oxygen therapy and hospitalisation. The drug was safe and well tolerated. Once death was an uncommon event, it is not possible to ensure that colchicine reduced mortality of COVID-19.Trial registration numberRBR-8jyhxh.

scholarly journals Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
John McCoy ◽  
Andy Goren ◽  
Flávio Adsuara Cadegiani ◽  
Sergio Vaño-Galván ◽  
Maja Kovacevic ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Outpatient Setting ◽  
Hospitalization Rate ◽  
Ordinal Scale ◽  
Controlled Clinical Trial ◽  
Intention To Treat ◽  
Androgen Receptor Antagonist ◽  
Male Patients ◽  
Double Blinded ◽  
Gastrointestinal Adverse Events

Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale &lt;3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P &lt; 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03–0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.

scholarly journals Proxalutamide (GT0918) Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial.

2021 ◽  
Author(s):  
John McCoy ◽  
Andy Goren ◽  
Flavio Adsuara Cadegiani ◽  
Sergio Vaño-Galván ◽  
Maja Kovacevic ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Outpatient Setting ◽  
Hospitalization Rate ◽  
Ordinal Scale ◽  
Controlled Clinical Trial ◽  
Intention To Treat ◽  
Androgen Receptor Antagonist ◽  
Double Blinded ◽  
Lost To Follow Up ◽  
Design And Methods

Abstract Background: Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. Study design and methods: A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (ClinicalTrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization.Results: A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P<0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03 to 0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost to follow-up, and 2 patients died from acute respiratory distress syndrome.Conclusion: The hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care. Trial Registration: NCT04446429

Prediction of preterm birth: the role cervical assessment by ultrasound and cervico-vaginal biomarkers

2020 ◽  
Author(s):  
Giuseppe Rizzo ◽  
Ilenia Mappa Mappa ◽  
Victoria Bitsadze ◽  
Jamilya Khizroeva ◽  
Alexander Makatsariya
Keyword(s):  
Preterm Birth ◽  
Neonatal Morbidity ◽  
Cervical Length ◽  
Fetal Fibronectin ◽  
Neonatal Deaths ◽  
A Value ◽  
Increased Risk ◽  
Asymptomatic Women

Preterm delivery (PTB) is one of the most common and serious complications of pregnancy. PTB accounts for approximately 70% of neonatal deaths and is a major cause of neonatal morbidity including respiratory distress syndrome, necrotising enterocolitis and long-term neurological disabilities. Prevention of PTB and its complications include identification among symptomatic women those at high risk of immediate delivery requiring prenatal corticosteroids administration. Transvaginal ultrasonographic evaluation of the cervical length (CL) is predictive of PTB and a value 15 mm identifies among symptomatic women approximately 70% of women who will deliver within one week. In the range of CL within 15 and 30 mm biomarkers n cervical-vaginal fluids (fetal fibronectin, phosphorylated insulin-like growth factor protein-1, placental alpha-microglobulin-, cytokines) and other ultrasonographic cervical variables (posterior cervical angle, elastography) improve the identification of women at risk, In asymptomatic women CL can be applied as screening and has been proposed as a universal screening during the second trimester in singleton gestations. The finding of a CL25mm is associated with an increased risk of subsequent PTB with a sensitivity between 30 and 60% that is improved with the combination of biomarkers. Asymptomatic women with a CL 25mm should be offered vaginal progesterone treatment for the prevention of preterm birth and neonatal morbidity. The role of cerclage and pessary is still controversial. In this review we discuss the evidence-based role of ultrasonographic cervical assessment and cervicovaginal biomarkers in the prediction of PTB in symptomatic and asymptomatic women

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