scholarly journals An epitope-based approach to use of HLA matched platelets for transfusion: a noninferiority, cross-over, randomised trial

Blood ◽  
2020 ◽  
Author(s):  
Judith C Marsh ◽  
Simon Stanworth ◽  
Laura Anne Pankhurst ◽  
Delordson Kallon ◽  
Adeline Gilbertson ◽  
...  
Keyword(s):  
Randomised Trial ◽  
Random Order ◽  
Adverse Outcomes ◽  
Bleeding Events ◽  
Eligibility Criteria ◽  
Donor Pool ◽  
Double Blind ◽  
Hla Antigen ◽  
Intention To Treat ◽  
Transfusion Requirements

Platelet transfusion refractoriness results in adverse outcomes and increased healthcare costs. Managing refractoriness due to HLA alloimmunization necessitates the use of HLA antigen matched platelets, but requires a large platelet donor pool, and does not guarantee full matching. We report the first ever randomized, double-blind, non-inferiority, cross-over trial comparing HLA epitope-matched (HEM) platelets with HLA standard antigen-matched (HSM) platelet transfusions. Eligibility criteria were alloimmunized, platelet refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome or acute myeloid leukemia. HEM platelets were selected using HLAMatchMaker epitope (specifically eplet) matching. Patients received up to eight prophylactic HEM and HSM transfusions provided in random order. Primary outcome was one-hour post transfusion platelet count increment (PCI). 49 patients were randomized at 14 UK hospitals. For intention-to-treat, number of evaluable transfusions was 107 and 112 for HEM and HSM, respectively. Unadjusted mean (SD) PCI for HEM and HSM was 23.9 (15) and 23.5 (14.1) respectively (adjusted mean difference -0.1, 95% CI -2.9, 2.8). As the lower limit of 95% CI was not greater than pre-defined non-inferiority limit, HEM was declared non-inferior to HSM. There were no differences in secondary outcomes of platelet counts, transfusion requirements and bleeding events. Adequate one-hour PCI was more frequently observed with a mean number of 3.2 of epitope mismatches compared to 5.5 epitope mismatches for inadequate one-hour increments. For every additional one epitope mismatch, the likelihood of an adequate PCI decreased by 15%. Epitope matched platelets should be considered to support HLA alloimmunized patients. Funded by NHS Blood and Transplant, ISRCTN23996532.

scholarly journals Cryotherapy associated with tailored land-based exercises for knee osteoarthritis: a protocol for a double-blind sham-controlled randomised trial

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e035610 ◽  
Author(s):  
Lucas Ogura Dantas ◽  
Ana Elisa Serafim Jorge ◽  
Paula Regina Mendes da Silva Serrão ◽  
Francisco Aburquerque-Sendín ◽  
Tania de Fatima Salvini
Keyword(s):  
Knee Osteoarthritis ◽  
Short Form ◽  
Randomised Trial ◽  
Unmet Need ◽  
Residual Effects ◽  
Control Group ◽  
Therapeutic Exercise ◽  
Exercise Protocol ◽  
Double Blind ◽  
Intention To Treat

IntroductionThere is an unmet need to develop tailored therapeutic exercise protocols applying different treatment parameters and modalities for individuals with knee osteoarthritis (KOA). Cryotherapy is widely used in rehabilitation as an adjunct treatment due to its effects on pain and the inflammatory process. However, disagreement between KOA guidelines remains with respect to its recommendation status. The aim of this study is to verify the complementary effects of cryotherapy when associated with a tailored therapeutic exercise protocol for patients with KOA.Methods and analysisThis study is a sham-controlled randomised trial with concealed allocation and intention-to-treat analysis. Assessments will be performed at baseline and immediately following the intervention period. To check for residual effects of the applied interventions, 3-month and 6-month follow-up assessments will be performed. Participants will be community members living with KOA divided into three groups: (1) the experimental group that will receive a tailored therapeutic exercise protocol followed by a cryotherapy session of 20 min; (2) the sham control group that will receive the same regimen as the first group, but with sham packs filled with dry sand and (3) the active treatment control group that will receive only the therapeutic exercise protocol. The primary outcome will be pain intensity according to a Visual Analogue Scale. Secondary outcomes will be the Western Ontario & McMaster Universities Osteoarthritis Index; the Short-Form Health Survey 36; the 30-s Chair Stand Test; the Stair Climb test; and the 40-m fast-paced walk test.Ethics and disseminationThe trial was approved by the Institutional Ethics Committee of Federal University of São Carlos, São Paulo, Brazil. Registration approval number: CAAE: 65966617.9.0000.5504. The results will be published in peer-reviewed journals.Trial registration numberNCT03360500

Regular reassessment of bleeding risk using the HAS-BLED score reduces bleeding outcomes in a prospective cohort: a report from the mAFA II clinical trial extension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Guo ◽  
D Lane ◽  
Y Chen ◽  
G.Y.H Lip
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trial ◽  
Randomised Trial ◽  
Bleeding Risk ◽  
Adverse Outcomes ◽  
Dynamic Monitoring ◽  
Antiplatelet Drug ◽  
Global Health Research ◽  
Funding Source ◽  
Bleeding Events

Abstract Background The HAS-BLED score was introduced to draw attention to modifiable bleeding risk factors and to identify patients with atrial fibrillation (AF) at high-risk of bleeding for early review and follow-up. The mAFA-II randomised trial reported that a holistic management strategy using App-based mobile Health technology support reduced AF-related adverse outcomes, compared to usual care. Objective To assess whether regular reassessment of bleeding risk using the HAS-BLED score would improve bleeding outcomes and oral anticoagulation (OAC) uptake. Methods Data for this analysis was drawn from the mAF App intervention arm. Bleeding risk (HAS-BLED score) and stroke risk (CHA2DS2-VASc score) were monitored prospectively using mAFA, and calculated during 4 periods: 1–30 days, 31–60 days, 61–180 days, and 181–365 days. Clinical events and OAC changes in relation to the dynamic monitoring and reassessments were analysed. Results We studied 1793 patients with AF (mean age 64 years, 32.5% female). The average number of re-assessments of CHA2DS2-VASc and HAS-BLED scores were 6.8 (SD 4.0) and 6.8 (4.1), respectively. Comparing baseline and 12 months, the proportion of AF patients with HAS-BLED ≥3 decreased (11.8% vs. 8.5%, p=0.008), with changes in use of concomitant NSAIDs/antiplatelets, renal dysfunction, and labile international normalized ratio (INR) contributing to the decreased proportion of patients with HAS-BLED ≥3 temporally (p<0.05). Use of non-vitamin K antagonist oral anticoagulants (NOAC), warfarin, and any antiplatelet drug was 47.1%, 13.8%, and 15.5%, respectively, at baseline. Incident bleeding events decreased significantly from 1–30 days to 181–365 days (1.2% to 0.2%, respectively; Table 1). Warfarin and NOAC use increased significantly over this period (17.9% to 18.4% and 46.4% to 51.8%, respectively). Conclusion In this clinical trial cohort, dynamic risk monitoring and reassessment using the HAS-BLED score, together with holistic App-based management using mAFA II reduced bleeding events, addressed modifiable bleeding risks and increased uptake of OACs. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China (H2501), NIHR Global Health Research Group on Atrial Fibrillation management

scholarly journals Efficacy of UVC-treated, pathogen-reduced platelets versus untreated platelets: a randomized controlled non-inferiority trial

Haematologica ◽  
2021 ◽  
Author(s):  
Veronika Brixner ◽  
Gesine Bug ◽  
Petra Pohler ◽  
Doris Krämer ◽  
Bernd Metzner ◽  
...  
Keyword(s):  
Platelet Transfusion ◽  
Primary Objective ◽  
Severe Bleeding ◽  
Low Grade ◽  
Bleeding Events ◽  
Double Blind ◽  
Intention To Treat ◽  
Randomized Controlled ◽  
Red Blood Cell Transfusions ◽  
Mean Differences

Pathogen reduction (PR) technologies for blood components have been established to reduce the residual risk of known and emerging infectious agents. THERAFLEX UVPlatelets, a novel UVC light-based PR technology for platelet concentrates, works without photoactive substances. This randomized, controlled, double-blind, multicenter, noninferiority trial was designed to compare the efficacy and safety of UVC-treated platelets to that of untreated platelets in thrombocytopenic patients with hematologic-oncologic diseases. Primary objective was to determine non-inferiority of UVC-treated platelets, assessed by the 1-hour corrected count increment (CCI) in up to eight per-protocol platelet transfusion episodes. Analysis of the 171 eligible patients showed that the defined non-inferiority margin of 30% of UVC-treated platelets was narrowly missed as the mean differences in 1-hour CCI between standard platelets versus UVC-treated platelets for intention-to-treat and perprotocol analyses were 18.2% (95% confidence interval [CI]: 6.4%; 30.1) and 18.7% (95% CI: 6.3%; 31.1%), respectively. In comparison to the control, the UVC group had a 19.2% lower mean 24-hour CCI and was treated with an about 25% higher number of platelet units, but the average number of days to next platelet transfusion did not differ significantly between both treatment groups. The frequency of low-grade adverse events was slightly higher in the UVC group and the frequencies of refractoriness to platelet transfusion, platelet alloimmunization, severe bleeding events, and red blood cell transfusions were comparable between groups. Our study suggests that transfusion of pathogen-reduced platelets produced with the UVC technology is safe but non-inferiority was not demonstrated. (The German Clinical Trials Register number: DRKS00011156).

scholarly journals Is It Useful To Treat Blastocystis sp.? A double-blind placebo-controlled randomised trial

2020 ◽  
Author(s):  
Ludovico Cobuccio ◽  
Marie Laurent ◽  
Celine Gardiol ◽  
Rahel Wampfler ◽  
Sven Poppert ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Randomised Trial ◽  
Parasitic Infection ◽  
Gastrointestinal Symptoms ◽  
Primary Objective ◽  
Care Physician ◽  
Eligibility Criteria ◽  
Entamoeba Dispar ◽  
Double Blind ◽  
Significant Difference

Abstract BackgroundBlastocystis sp. is a protist with a worldwide distribution and able to colonise the gut of humans and of a great variety of animals. It is unclear whether it is just a commensal of a healthy gut microbiota or an infectious parasite that needs to be eradicated. Currently no treatment has proven its usefulness for patients complaining of gastro-intestinal symptoms and found to have Blastocystis sp.The primary objective of this study was to evaluate the usefulness of metronidazole in patients with gastrointestinal symptoms harbouring only Blastocystis sp. In addition, we explored whether Blastocystis subtype or concomitant parasitic infection detected by polymerase chain reaction (PCR) may influence treatment outcome.MethodsAdults with persistent gastrointestinal symptoms (> 14 days) visiting a primary care physician and in whom stool microscopy revealed only Blastocystis sp. were included. Eligible patients were randomised to receive ten days of metronidazole or placebo, followed by a crossover if still symptomatic. Stool samples were tested for 11 other protozoa with an in-house PCR and Blastocystis subtypes were determined by PCR and sequencing.ResultsWe screened 474 outpatients for inclusion; 50 met the eligibility criteria. In the metronidazole group, 48% (12/25) reported an improvement of symptoms compared to 44% (11/25) in the placebo group (p = 0.78). After the crossover, again no differences in improvement of symptoms were seen between groups (placebo: 53% (8/15); metronidazole: 50% (8/16)). The in-house PCR was positive for other protozoa in 25% (10/40) of the patients. The protozoa identified were Dientamoeba fragilis (5), Entamoeba dispar (3) and Cyclospora cayetanensis (2). The most frequent Blastocystis subtypes were ST4 (11/36) and ST2 (10/36). Stratified analysis according to subtype or the presence of other protozoa showed no significant difference in treatment outcome with metronidazole or placebo.Conclusion Among patients infected with Blastocystis sp., metronidazole did not improve gastrointestinal symptoms, irrespective of subtype or microscopically undetected coinfection with other protozoa.Trial registrationClinicalTrials.gov: NTC01521403, 06-Nov-2012.

A Comparative, Double-blind, Randomised Trial of a New Second Generation LMWH (Bemiparin) and UFH in the Prevention of Post-operative Venous Thromboembolism

2000 ◽  
Vol 83 (04) ◽  
pp. 523-529 ◽  
Author(s):  
J. Howes ◽  
V. Sharma ◽  
Z. Kadziola ◽  
V. V. Kakkar ◽  
Keyword(s):  
Venous Thromboembolism ◽  
Hip Arthroplasty ◽  
Randomised Trial ◽  
Factor Xa ◽  
Bleeding Complications ◽  
Bleeding Events ◽  
Double Blind ◽  
Subcutaneous Dose ◽  
Number Of Patients ◽  
Risk Patients

SummaryA randomised, prospective, double-blind trial was performed, to compare the safety and efficacy of a new low-molecular-weight heparin (LMWH) Bemiparin and standard unfractionated heparin (UFH), for the prophylaxis of postoperative venous thromboembolism. 300 patients scheduled to undergo elective hip arthroplasty were included. The principal outcome measures were the incidence of thromboembolic events and bleeding complications. 149 patients received 3,500 anti-Xa IU of bemiparin plus a placebo injection daily and 149 patients received 5,000 IU of UFH twice a day.The two groups were similar with respect to factors likely to affect the risk of developing post-operative venous thromboembolism (VTE) and risk of bleeding events. During the post-operative period, 34 patients developed VTE complications; 9 (7.2%) in the bemiparin group and 25 (18.7%) in the UFH group. VTE in the two groups was statistically significant (OR of 2.96; 95% CI 1.32-6.62 and p = 0.01).There were no significant differences in the frequency of bleeding complications: major bleeding requiring discontinuation of prophylaxis, (OR 1.21; 95% CI 0.36-4.05; p = 1.00), the measured median operative blood loss (p = 0.77) or the median postoperative drain loss (p = 0.97), and the number of patients who developed wound haematoma (OR 0.87; 95% CI 0.31-2.46; p = 1.00).A comparison of coagulation parameters on the preoperative day with post-operative day 2 ± 1, day 6 ± 1 and day of discharge showed a significantly higher AT concentration, anti-factor Xa activity and TFPI levels in the bemiparin group when compared with UFH.This study demonstrates that bemiparin, in a single daily subcutaneous dose of 3,500 anti-Xa IU in high risk patients undergoing hip arthroplasty is more effective than UFH administered twice daily at a dose of 5,000 IU in the prevention of postoperative VTE. Both agents are equally safe.List of participants, their affiliations and current addresses are listed in the appendix on p. 528

scholarly journals TELO-SCOPE study: a randomised, double-blind, placebo-controlled, phase 2 trial of danazol for short telomere related pulmonary fibrosis

2021 ◽  
Vol 8 (1) ◽  
pp. e001127
Author(s):  
John A Mackintosh ◽  
Maria Pietsch ◽  
Viviana Lutzky ◽  
Debra Enever ◽  
Sandra Bancroft ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Telomere Length ◽  
In Situ Hybridisation ◽  
Randomised Trial ◽  
Standard Of Care ◽  
Dyskeratosis Congenita ◽  
Fluorescence In Situ Hybridisation ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Intention To Treat

IntroductionRecent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening.Methods and analysisA multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged >5 years with PF associated with age-adjusted telomere length ≤10th centile measured by flow fluorescence in situ hybridisation; or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800 mg daily in two divided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2 mg/kg/day orally in two divided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4 mg/kg/day (maximum 800 mg daily) orally in two divided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population.Ethics and disseminationEthics approval has been granted in Australia by the Metro South Human Research Ethics Committee (HREC/2020/QMS/66385). The study will be conducted and reported according to Standard Protocol Items: Recommendations for Interventional Trials guidelines. Results will be published in peer-reviewed journals and presented at international and national conferences.Trial registration numbersNCT04638517; Australian New Zealand Clinical Trials Registry (ACTRN12620001363976p).

The Effect of Desmopressin on Reducing Blood Loss in Cardiac Surgery – A Meta-Analysis of Double-Blind, Placebo-Controlled Trials

1995 ◽  
Vol 74 (04) ◽  
pp. 1064-1070 ◽  
Author(s):  
Marco Cattaneo ◽  
Alan S Harris ◽  
Ulf Strömberg ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Cardiac Surgery ◽  
Blood Loss ◽  
Meta Analysis ◽  
Postoperative Blood Loss ◽  
Controlled Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Transfusion Requirements ◽  
The Mean ◽  
Excessive Blood Loss

SummaryThe effect of desmopressin (DDAVP) on reducing postoperative blood loss after cardiac surgery has been studied in several randomized clinical trials, with conflicting outcomes. Since most trials had insufficient statistical power to detect true differences in blood loss, we performed a meta-analysis of data from relevant studies. Seventeen randomized, double-blind, placebo-controlled trials were analyzed, which included 1171 patients undergoing cardiac surgery for various indications; 579 of them were treated with desmopressin and 592 with placebo. Efficacy parameters were blood loss volumes and transfusion requirements. Desmopressin significantly reduced postoperative blood loss by 9%, but had no statistically significant effect on transfusion requirements. A subanalysis revealed that desmopressin had no protective effects in trials in which the mean blood loss in placebo-treated patients fell in the lower and middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in trials in which the mean blood loss in placebo-treated patients fell in the upper third of distribution (>1109 ml/24 h), desmopressin significantly decreased postoperative blood loss by 34%. Insufficient data were available to perform a sub-analysis on transfusion requirements. Therefore, desmopressin significantly reduces blood loss only in cardiac operations which induce excessive blood loss. Further studies are called to validate the results of this meta-analysis and to identify predictors of excessive blood loss after cardiac surgery.

Pharmacokinetics and Tolerability of Factor XIII Concentrates Prepared from Human Placenta or Plasma: a Crossover Randomised Study

1995 ◽  
Vol 74 (02) ◽  
pp. 622-625 ◽  
Author(s):  
H H Brackmann ◽  
R Egbring ◽  
A Ferster ◽  
P Fondu ◽  
J M Girardel ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Bleeding Events ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Randomised Study ◽  
The Mean ◽  
Blind Crossover Study ◽  
Double Blind Crossover Study ◽  
Fxiii Activity ◽  
Observation Period

SummaryThe pharmacokinetics and tolerability of factor XIII (FXIII) from plasma were compared with those of FXIII from placenta in a randomised, double-blind, crossover study involving 13 patients with congenital FXIII deficiency. Both FXIII activity and FXIII antigen were monitored. No difference was seen in the mean half-lives of the two preparations (9.3 days and 9.1 days for plasma and placenta FXIII activity, respectively). Response was similar for both preparations, but was slightly greater for FXIII from plasma.Similar results were found for recovery (65% vs 60%). The area under the data completed by extrapolation was significantly higher for FXIII from plasma. No differences between preparations in terms of efficacy or tolerability were observed. It can be concluded that treatment with FXIII concentrate from plasma is as efficient as with FXIII concentrate from placenta in terms of recovery and half-life. Both preparations were equivalent in terms of safety during the observation period. With the administration of monthly injections of approximately 30 U/kg serious bleeding events were prevented and no other serious adverse events occurred.

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