scholarly journals Weekly iron–folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia

2020 ◽  
Vol 5 (12) ◽  
pp. e003897
Author(s):  
Kaitlyn L I Samson ◽  
Su Peng Loh ◽  
Siew Siew Lee ◽  
Dian C Sulistyoningrum ◽  
Geok Lin Khor ◽  
...  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Controlled Trial ◽  
Clinical Trial Registry ◽  
Double Blind ◽  
Folic Acid Supplements ◽  
Registration Number ◽  
Menstruating Women ◽  
Iron Folic Acid ◽  
Randomised Controlled

IntroductionWeekly iron–folic acid (IFA) supplements are recommended for all menstruating women in countries where anaemia prevalence is >20%. Anaemia caused by folate deficiency is low worldwide, and the need to include folic acid is in question. Including folic acid might reduce the risk of a neural tube defect (NTD) should a woman become pregnant. Most weekly supplements contain 0.4 mg folic acid; however, WHO recommends 2.8 mg because it is seven times the daily dose effective in reducing NTDs. There is a reluctance to switch to supplements containing 2.8 mg of folic acid because of a lack of evidence that this dose would prevent NTDs. Our aim was to investigate the effect of two doses of folic acid, compared with placebo, on red blood cell (RBC) folate, a biomarker of NTD risk.MethodsWe conducted a three-arm double-blind efficacy trial in Malaysia. Non-pregnant women (n=331) were randomised to receive 60 mg iron and either 0, 0.4, or 2.8 mg folic acid once weekly for 16 weeks.ResultsAt 16 weeks, women receiving 0.4 mg and 2.8 mg folic acid per week had a higher mean RBC folate than those receiving 0 mg (mean difference (95% CI) 84 (54 to 113) and 355 (316 to 394) nmol/L, respectively). Women receiving 2.8 mg folic acid had a 271 (234 to 309) nmol/L greater mean RBC folate than those receiving 0.4 mg. Moreover, women in the 2.8 mg group were seven times (RR 7.3, 95% CI 3.9 to 13.7; p<0.0001) more likely to achieve an RBC folate >748 nmol/L, a concentration associated with a low risk of NTD, compared with the 0.4 mg group.ConclusionWeekly IFA supplements containing 2.8 mg folic acid increases RBC folate more than those containing 0.4 mg. Increased availability and access to the 2.8 mg formulation is needed.Trail registration numberThis trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619000818134).

scholarly journals Naoxuekang, Xinnaoshutong and Xuesaitong capsules for treating stroke: a protocol for a randomised controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. e015983 ◽  
Author(s):  
Huiling Chen ◽  
Hongbo Cao ◽  
Xu Guo ◽  
Meidan Zhao ◽  
Qing Xia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Facial Paralysis ◽  
Controlled Trial ◽  
Clinical Trial Registry ◽  
Double Blind ◽  
Initial Treatment Period ◽  
Double Blind Clinical Trial ◽  
Registration Number ◽  
Index Value ◽  
Randomised Controlled

IntroductionAfter stroke, hemiplegia, dysphasia and facial paralysis can manifest during the convalescent period. Currently, no Chinese patent medicine (CPM) is previously reported to cure each of these symptoms primarily, and thus, there are no relevant instructions for the use of CPM. This study presents a new approach based on comparative effectiveness research to distinguish the curative effects of three CPMs that are often used in stroke convalescence to determine the ideal medicine for the treatment of each symptom.Methods and analysisIn this multicentre and double-blind clinical trial, stratified randomisation is used to group the patients according to their primary symptoms (hemiplegia, dysphasia and facial paralysis). Three strata will be enrolled, with 80 eligible participants included in each stratum. Each stratum will be randomly and equally divided into four groups, and each group will receive one of the following treatments: Naoxuekang, Xinnaoshutong (XNST), Xuesaitong (XST) or placebo. This study will include two stages: the initial treatment period (30 days) and a follow-up period (180 days). Three replicates for each data point will be completed during this trial. The first visit will occur on day 0 after enrolment, the second visit on day 30±2 and the third visit on day 210±5. The Delphi technique is adopted to achieve index weighting, which ensures that the evaluation outcome is patient oriented. The weighted index value will be computed as the final measurement index of the outcome.Ethics and disseminationThis study has been approved by the Medical Ethics Committee of Tianjin University of Traditional Chinese Medicine (registration number TJUTCM-EC20160007). The results will be offered for publication in peer-reviewed journals.Trial registration numberThis trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-17010397). The date of registration was 11 January 2017.

scholarly journals Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)

2017 ◽  
Vol 77 (2) ◽  
pp. 212-220 ◽  
Author(s):  
Dinesh Khanna ◽  
Christopher P Denton ◽  
Celia J F Lin ◽  
Jacob M van Laar ◽  
Tracy M Frech ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Phase Ii ◽  
Controlled Trial ◽  
Safety Data ◽  
Open Label ◽  
Double Blind ◽  
Skin Score ◽  
Open Label Extension ◽  
Registration Number ◽  
Randomised Controlled

ObjectivesAssess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study.MethodsPatients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96.ResultsOverall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was –3.1 (6.3 (–5.4 to –0.9)) for placebo and –5.6 (9.1 (–8.9 to–2.4)) for tocilizumab at week 48 and –9.4 (5.6 (–8.9 to –2.4)) for placebo-tocilizumab and –9.1 (8.7 (–12.5 to –5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had >10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period.ConclusionsSkin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab.Trial registration numberNCT01532869; Results.

scholarly journals Can topical epinephrine application to the papilla prevent pancreatitis after endoscopic retrograde cholangiopancreatography? Results from a double blind, multicentre, placebo controlled, randomised clinical trial

2021 ◽  
Vol 8 (1) ◽  
pp. e000562
Author(s):  
Adriana Fabiola Romano-Munive ◽  
J Jesus García-Correa ◽  
Luis F García-Contreras ◽  
José Ramírez-García ◽  
Luis Uscanga ◽  
...  
Keyword(s):  
Endoscopic Retrograde Cholangiopancreatography ◽  
Controlled Trial ◽  
Randomised Clinical Trial ◽  
Sterile Water ◽  
Endoscopic Retrograde ◽  
Double Blind ◽  
Registration Number ◽  
Baseline Characteristics ◽  
Randomised Controlled ◽  
Rectal Indomethacin

Background and study aimsPost-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a complication associated with important morbidity, occasional mortality and high costs. Preventive strategies are suboptimal as PEP continues to affect 4% to 9% of patients. Spraying epinephrine on the papilla may decrease oedema and prevent PEP. This study aimed to compare rectal indomethacin plus epinephrine (EI) versus rectal indomethacin plus sterile water (WI) for the prevention of PEP.Patients and methodsThis multicentre randomised controlled trial included patients aged >18 years with an indication for ERCP and naive major papilla. All patients received 100 mg of rectal indomethacin and 10 mL of sterile water or a 1:10 000 epinephrine dilution. Patients were asked about PEP symptoms via telephone 24 hours and 7 days after the procedure. The trial was stopped half way through after a new publication reported an increased incidence of PEP among patients receiving epinephrine.ResultsOf the 3602 patients deemed eligible, 3054 were excluded after screening. The remaining 548 patients were randomised to EI group (n=275) or WI group (n=273). The EI and WI groups had similar baseline characteristics. Patients in the EI group had a similar incidence of PEP to those in the WI group (3.6% (10/275) vs 5.12% (14/273), p=0.41). Pancreatic duct guidewire insertion was identified as a risk factor for PEP (OR 4.38, 95% CI (1.44 to 13.29), p=0.009).ConclusionSpraying epinephrine on the papilla was no more effective than rectal indomethacin alone for the prevention of PEP.Trial registration numberThis study was registered with ClinicalTrials.gov (NCT02959112).

scholarly journals Effect of tranexamic acid on the prognosis of patients with traumatic brain injury undergoing craniotomy: study protocol for a randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e049839
Author(s):  
Bei Wu ◽  
Yu Lu ◽  
Yun Yu ◽  
Hongli Yue ◽  
Jie Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Tranexamic Acid ◽  
Controlled Trial ◽  
Perioperative Period ◽  
Double Blind ◽  
Ethical Approval ◽  
Registration Number ◽  
Randomised Controlled ◽  
Medical University

IntroductionAbnormal coagulation function aggravates the prognosis of patients with traumatic brain injury (TBI). It was reported that the antifibrinolytic drug tranexamic acid (TXA) could reduce intracranial haemorrhage and mortality in non-operative patients with TBI. However, there is a lack of evaluation of TXA in patients with TBI undergoing craniotomy.Methods and analysisThis is a single-centre randomised controlled, double-blind, parallel study aiming to investigate the effectiveness and safety of TXA in patients with TBI during the perioperative period. Blood loss and transfusion, neurological function, adverse events, mortality and serum immune-inflammatory cytokines will be collected and analysed.Ethics and disseminationEthical approval has been granted by the Medical Ethics Committee of Beijing Tian Tan Hospital, Capital Medical University (reference number KY 2020-136-03). The results of this study will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals.Trial registration numberChiCTR2100041911.

Intravenous cefazolin plus oral probenecid versus oral cephalexin for the treatment of skin and soft tissue infections: a double-blind, non-inferiority, randomised controlled trial

2018 ◽  
Vol 35 (8) ◽  
pp. 492-498 ◽  
Author(s):  
Dawn Dalen ◽  
Amy Fry ◽  
Samuel G Campbell ◽  
Jeffrey Eppler ◽  
Peter J Zed
Keyword(s):  
Soft Tissue ◽  
Clinical Cure ◽  
Controlled Trial ◽  
Tertiary Care ◽  
Risk Difference ◽  
Teaching Hospitals ◽  
Double Blind ◽  
Treatment Groups ◽  
Registration Number ◽  
Randomised Controlled

ObjectiveThe purpose of our study was to determine if cephalexin 500 mg orally four times daily was non-inferior to cefazolin 2 g intravenously daily plus probenecid 1 g orally daily in the management of patients with uncomplicated mild–moderate skin and soft tissue infection (SSTI) presenting to the ED.MethodsThis was a prospective, multicentre, double dummy-blind, randomised controlled non-inferiority trial conducted at two tertiary care teaching hospitals in Canada. Patients were enrolled if they presented to the ED with an uncomplicated SSTI, and randomly assigned in a 1:1 fashion to oral cephalexin or intravenous cefazolin plus oral probenecid for up to 7 days. The primary outcome was failure of therapy at 72 hours. Clinical cure at 7 days, intravenous to oral medication transition admission to hospital and adverse events were also evaluated.Results206 patients were randomised with 104 patients in the cephalexin group and 102 in the cefazolin and probenecid group. The proportion of patients failing therapy at 72 hours was similar between the treatment groups (4.2% and 6.1%, risk difference 1.9%, 95% CI −3.7% to 7.6%). Clinical cure at 7 days was not significantly different (100% and 97.7%, risk difference −2.3%, 95% CI −6.7% to 0.8%).ConclusionCephalexin at appropriate doses appears to be a safe and effective alternative to outpatient parenteral cefazolin in the treatment of uncomplicated mild–moderate SSTIs who present to the ED.Trial registration numberNCT01029782; Results.

scholarly journals Effect of once weekly folic acid supplementation on erythrocyte folate concentrations in women to determine potential to prevent neural tube defects: a randomised controlled dose-finding trial in Malaysia

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e034598
Author(s):  
Kaitlyn L I Samson ◽  
Su Peng Loh ◽  
Geok Lin Khor ◽  
Zalilah Mohd Shariff ◽  
Lisa N Yelland ◽  
...  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Controlled Trial ◽  
Folic Acid Supplementation ◽  
Dose Finding ◽  
Baseline Measure ◽  
Intention To Treat ◽  
Erythrocyte Folate ◽  
Randomised Controlled

IntroductionFolic acid (0.4 mg) taken prior to and during early pregnancy reduces the risk of neural tube defects (NTDs). Because these birth defects occur early in pregnancy, before women may know they are pregnant, many countries have mandated the addition of folic acid to food staples. In countries where fortification is not possible, and weekly iron folic acid programmes exist to reduce anaemia, the WHO recommends that 2.8 mg (7×0.4 mg) folic acid be given instead of the current weekly practice of 0.4 mg. Currently, there is a lack of evidence to support if the 2.8 mg folic acid per week dose is sufficient to raise erythrocyte folate concentrations to a level associated with a reduced risk of a NTD-affected pregnancy. We aim to conduct a three-arm randomised controlled trial to determine the effect of weekly folic acid with iron on erythrocyte folate, a biomarker of NTD risk.Methods and analysisWe will recruit non-pregnant women (n=300; 18–45 years) from Selangor, Malaysia. Women will be randomised to receive either 2.8, 0.4 or 0.0 (placebo) mg folic acid with 60 mg iron weekly for 16 weeks, followed by a 4-week washout period. The primary outcome will be erythrocyte folate concentration at 16 weeks and the mean concentration will be compared between randomised treatment groups (intention-to-treat) using a linear regression model adjusting for the baseline measure.Ethics and disseminationEthical approval was obtained from the University of British Columbia (H18-00768) and Universiti Putra Malaysia (JKEUPM-2018-255). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals.Trial registration numbersACTRN12619000818134 and NMRR-19-119-45736.

scholarly journals Modifying effects of maternal Hb concentration on infant birth weight in women receiving prenatal iron-containing supplements: a randomised controlled trial

2015 ◽  
Vol 115 (4) ◽  
pp. 644-649 ◽  
Author(s):  
Linlin Wang ◽  
Zuguo Mei ◽  
Hongtian Li ◽  
Yali Zhang ◽  
Jianmeng Liu ◽  
...  
Keyword(s):  
Folic Acid ◽  
Birth Weight ◽  
Randomised Controlled Trial ◽  
Pregnant Women ◽  
Controlled Trial ◽  
Double Blind ◽  
Randomised Controlled ◽  
Hb Concentration ◽  
Infant Birth ◽  
Very High

AbstractConcerns have been raised about the benefits of Fe-containing supplements on infant birth weight among women with normal/high Hb levels at baseline. Thus far, no clinical trials have examined whether the effects of prenatal Fe-containing supplements on birth weight vary by maternal Hb levels. We compared the effects of Fe–folic acid (IFA) or multiple micronutrients (MMN) with folic acid (FA) supplements on birth weight among pregnant women with mild/no anaemia or high Hb levels. A double-blind randomised controlled trial was conducted in 2006–2009. In total, 18 775 pregnant women with mild/no anaemia (<100 g/l) were enrolled from five counties in north China. During the period from before 20 weeks of gestation to delivery, the women randomly received a daily supplement containing the following: (1) FA (400 μg); (2) IFA (FA, 400 μg; Fe, 30 mg); or (3) MMN (FA, Fe and thirteen additional vitamins and minerals). Birth weight was measured within the 1st hour of birth. Maternal Hb concentration was determined at enrolment. Among women with normal (≤132 g/l) or high (133–145 g/l) baseline Hb levels, IFA or MMN supplementation had no effect on birth weight. Among women with very high (>145 g/l) baseline Hb levels, IFA and MMN supplements increased birth weight by 91·44 (95 % CI 3·37, 179·51) g and 107·63 (95 % CI 21·98, 193·28) g (P<0·05), respectively, compared with the FA group. No differences were found between the IFA and the MMN group, regardless of maternal Hb concentration. In conclusion, the effects of Fe-containing supplements on birth weight depended on baseline Hb concentrations. The Fe-containing supplements improved birth weight in women with very high Hb levels before 20 weeks of gestation.

scholarly journals Study protocol for a randomised controlled trial evaluating the effect of folic acid supplementation beyond the first trimester on maternal plasma unmetabolised folic acid in late gestation

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040416
Author(s):  
Dian Sulistyoningrum ◽  
Tim Green ◽  
Debbie Palmer ◽  
Thomas Sullivan ◽  
Simon Wood ◽  
...  
Keyword(s):  
Folic Acid ◽  
Randomised Controlled Trial ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Controlled Trial ◽  
Folic Acid Supplementation ◽  
Autism Spectrum ◽  
Late Gestation ◽  
Acid Supplementation ◽  
Randomised Controlled

IntroductionTaking folic acid containing supplements prior to and during early pregnancy reduces the risk of neural tube defects. Neural tube defects occur prior to 28 days postconception, after which, there is no proven benefit of continuing to take folic acid. However, many women continue to take folic acid containing supplements throughout the pregnancy. At higher intakes, folic acid is not converted to its active form and accumulates in circulation as unmetabolised folic acid (UMFA). Recently, concerns have been raised about possible links between late gestation folic acid supplementation and childhood allergy, metabolic disease and autism spectrum disorders. We aim to determine if removing folic acid from prenatal micronutrient supplements after 12 weeks gestation reduces circulating levels of maternal UMFA at 36 weeks gestation.Methods and analysisThis is a parallel-design, double-blinded randomised controlled trial. Women ≥12 and <16 weeks’ gestation with a singleton pregnancy and able to give informed consent are eligible to participate. Women (n=100; 50 per group) will be randomised to receive either a micronutrient supplement containing 0.8 mg of folic acid or a micronutrient supplement without folic acid daily from enrolment until delivery. The primary outcome is plasma UMFA concentration at 36 weeks gestation. Secondary outcomes include red blood cell folate and total plasma folate concentration. We will assess whether there is a difference in mean UMFA levels at 36 weeks gestation between groups using linear regression with adjustment for baseline UMFA levels and gestational age at trial entry. The treatment effect will be described as a mean difference with 95% CI.Ethics and disseminationEthical approval has been granted from the Women’s and Children’s Health Network Research Ethics Committee (HREC/19/WCHN/018). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals.Trial registration numberACTRN12619001511123.

scholarly journals Early PARacetamol (EPAR) trial: a study protocol for a randomised controlled trial of early paracetamol to promote closure of the ductus arteriosus in preterm infants

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e031428 ◽  
Author(s):  
Tim Schindler ◽  
John Smyth ◽  
Srinivas Bolisetty ◽  
Joanna Michalowski ◽  
Kei Lui
Keyword(s):  
Preterm Infants ◽  
Controlled Trial ◽  
Ductus Arteriosus ◽  
Primary Analysis ◽  
Double Blind ◽  
Safe Alternative ◽  
Target Sample Size ◽  
Intravenous Paracetamol ◽  
Registration Number ◽  
Randomised Controlled

IntroductionThe optimal management of patent ductus arteriosus (PDA) remains contentious. The medications used to treat PDA are often non-steroidal anti-inflammatory drugs, which are associated with a number of unwanted adverse effects. Paracetamol is a medication with an excellent safety profile in infants and has been suggested as a safe alternative medication in situations where other medications have failed or are contraindicated. There are limited data on the use of early, intravenous paracetamol in preterm infants.Methods and analysisThis trial aims to address whether early treatment with paracetamol will reduce the number of infants requiring intervention for PDA. This is a randomised, double-blind, placebo-controlled trial in preterm infants <29 weeks’ gestation. At 6 hours of life, infants with a ductus arteriosus >0.9 mm will be randomised to receive either (1) intravenous paracetamol at a dose of 15 mg/kg initially, followed by every 6 hours at a dose of 7.5 mg/kg for 5 days; or (2) intravenous 5% dextrose every 6 hours for 5 days. The primary outcome is the need for any intervention for management of PDA up to 5 days. Secondary outcomes include closure of the ductus arteriosus at 5 days, size of the ductus arteriosus, ductal reopening, systemic blood flow, mortality and significant morbidities. The target sample size of 100 infants yields >80% power, at the two-sided 5% level significance, to detect a 50% reduction in the need for intervention assuming that approximately 60% of infants in this study would otherwise have required intervention for PDA.Ethics and disseminationA report on the results of the planned analyses will be prepared. The results of the primary analysis of all end points will be presented at medical conferences and submitted for publication in peer-reviewed journals. Separate manuscripts pertaining to the second aim of the study may be written, and these will also be submitted for publication in peer-reviewed journals.Trial registration numberACTRN12616001517460.

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