scholarly journals The effects of a limited infusion rate of fluid in the early resuscitation of sepsis on glycocalyx shedding measured by plasma syndecan-1: a randomized controlled trial

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jutamas Saoraya ◽  
Lipda Wongsamita ◽  
Nattachai Srisawat ◽  
Khrongwong Musikatavorn
Keyword(s):  
Adverse Events ◽  
Organ Failure ◽  
Fluid Resuscitation ◽  
Infusion Rate ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Endothelial Glycocalyx ◽  
Open Label ◽  
Randomized Controlled ◽  
Standard Rate

Abstract Background Aggressive fluid administration is recommended in the resuscitation of septic patients. However, the delivery of a rapid fluid bolus might cause harm by inducing degradation of the endothelial glycocalyx. This research aimed to examine the effects of the limited infusion rate of fluid on glycocalyx shedding as measured by syndecan-1 in patients with sepsis-induced hypoperfusion. Methods A prospective, randomized, controlled, open-label trial was conducted between November 2018 and February 2020 in an urban academic emergency department. Patients with sepsis-induced hypoperfusion, defined as hypotension or hyperlactatemia, were randomized to receive either the standard rate (30 ml/kg/h) or limited rate (10 ml/kg/h) of fluid for the first 30 ml/kg fluid resuscitation. Subsequently, the fluid rate was adjusted according to the physician’s discretion but not more than that of the designated fluid rate for the total of 6 h. The primary outcome was differences in change of syndecan-1 levels at 6 h compared to baseline between standard and limited rate groups. Secondary outcomes included adverse events, organ failure, and 90-day mortality. Results We included 96 patients in the intention-to-treat analysis, with 48 assigned to the standard-rate strategy and 48 to the limited-rate strategy. The median fluid volume in 6 h in the limited-rate group was 39 ml/kg (interquartile range [IQR] 35–52 ml/kg) vs. 53 ml/kg (IQR 46–64 ml/kg) in the standard-rate group (p < 0.001). Patients in the limited-rate group were less likely to received vasopressors (17% vs 42%; p = 0.007) and mechanical ventilation (20% vs 41%; p = 0.049) during the first 6 h. There were no significantly different changes in syndecan-1 levels at 6 h between the two groups (geometric mean ratio [GMR] in the limited-rate group, 0.82; 95% confidence interval [CI], 0.66–1.02; p = 0.07). There were no significant differences in adverse events, organ failure outcomes, or mortality between the two groups. Conclusions In sepsis resuscitation, the limited rate of fluid resuscitation compared to the standard rate did not significantly reduce changes in syndecan-1 at 6 h. Trial registration Thai Clinical Trials Registry number: TCTR20181010001. Registered 8 October 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=4064

A Randomized Controlled Trial to Investigate Safety and Variability of Egg Excretion After Repeated Controlled Human Hookworm Infection

2020 ◽  
Author(s):  
Marie-Astrid Hoogerwerf ◽  
Jan Pieter R Koopman ◽  
Jacqueline J Janse ◽  
Marijke C C Langenberg ◽  
Roos van Schuijlenburg ◽  
...  
Keyword(s):  
Adverse Events ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Egg Load ◽  
Infectious Dose ◽  
Randomized Controlled ◽  
Vaccine Trials ◽  
The Mean ◽  
Bayesian Statistical Modeling ◽  
Hookworm Infections

Abstract Background Controlled human hookworm infections could significantly contribute to the development of a hookworm vaccine. However, current models are hampered by low and unstable egg output, reducing generalizability and increasing sample sizes. This study aims to investigate the safety, tolerability, and egg output of repeated exposure to hookworm larvae. Methods Twenty-four healthy volunteers were randomized, double-blindly, to 1, 2, or 3 doses of 50 Necator americanus L3 larvae at 2-week intervals. Volunteers were monitored weekly and were treated with albendazole at week 20. Results There was no association between larval dose and number or severity of adverse events. Geometric mean egg loads stabilized at 697, 1668, and 1914 eggs per gram feces for the 1 × 50L3, 2 × 50L3, and 3 × 50L3 group, respectively. Bayesian statistical modeling showed that egg count variability relative to the mean was reduced with a second infectious dose; however, the third dose did not increase egg load or decrease variability. We therefore suggest 2 × 50L3 as an improved challenge dose. Model-based simulations indicates increased frequency of stool sampling optimizes the power of hypothetical vaccine trials. Conclusions Repeated infection with hookworm larvae increased egg counts to levels comparable to the field and reduced relative variability in egg output without aggravating adverse events. Clinical Trials Registration NCT03257072.

Efficacy and Safety of Ascending Dosages of Tribendimidine Against Hookworm Infections in Children: A Randomized Controlled Trial

2018 ◽  
Vol 69 (5) ◽  
pp. 845-852
Author(s):  
Jean T Coulibaly ◽  
Noemi Hiroshige ◽  
Yves K N’Gbesso ◽  
Jan Hattendorf ◽  
Jennifer Keiser
Keyword(s):  
Randomized Controlled Trial ◽  
Adverse Events ◽  
Clinical Symptoms ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Global Strategy ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Emax Model ◽  
Hookworm Infections

Abstract Background The global strategy to control soil-transmitted helminthiasis is mainly focused on preventive chemotherapy with albendazole and mebendazole. We assessed the efficacy and safety of ascending tribendimidine doses against hookworm infections in African school-aged children, key information for the development of tribendimidine. Methods We performed a single blind, randomized, controlled trial in Côte d’Ivoire between June and August 2017. Eligible participants were randomly assigned to placebo, 100, 200, or 400 mg tribendimidine. Cure rates (CRs, primary outcome) and egg reduction rates (ERRs) were determined 14–21 days after treatment. Clinical symptoms were assessed before treatment and adverse events monitored 3 and 24 hours posttreatment. Results CRs calculated for 130 children dose-dependently increased. The observed CRs were 20.6% (7/34), 21.2% (7/33), 38.7% (12/31), and 53.1% (17/32) for placebo, 100, 200, and 400 mg of tribendimidine, respectively. The Emax model predicted a placebo corrected net effect of 34.3 percentage points (95% confidence interval [CI], 13.3–54.4) for the 400-mg tribendimidine dose. The ERRs (geometric mean) were 30.6% (95% CI, −24.7 to 64.1), 65.4% (95% CI, 24.5–85.9), 82.1% (95% CI, 58.4–92.5) and 92.2% (95% CI, 81.0–97.1) for placebo, 100, 200, and 400 mg tribendimidine, respectively. The Emax model predicted an ERR of 95% at 500 mg. Only mild adverse events and no abnormal biochemical parameters were observed. Conclusion A 400-mg dose of tribendimidine yielded the highest efficacy and was well tolerated. Because children were mostly lightly infected, further investigations with tribendimidine against moderate/heavy hookworm infection are needed. Clinical Trials Registration The trial is registered at www.isrctn.com number ISRCTN81391471.

scholarly journals Restrictive versus liberal fluid resuscitation strategy, influence on blood loss and hemostatic parameters in mild obstetric hemorrhage: An open-label randomized controlled trial. (REFILL study)

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253765
Author(s):  
Pim B. B. Schol ◽  
Natascha M. de Lange ◽  
Mallory D. Woiski ◽  
Josje Langenveld ◽  
Luc J. M. Smits ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Blood Loss ◽  
Adverse Events ◽  
Fluid Resuscitation ◽  
Controlled Trial ◽  
Fluid Administration ◽  
Open Label ◽  
Coagulation Parameters ◽  
Management Group ◽  
Alternative Treatment Option

Background Evidence for optimal hemostatic resuscitation in postpartum hemorrhage (PPH) is lacking. Liberal fluid administration may result in acidosis, hypothermia and coagulopathy. Objective We hypothesize that in early PPH a restrictive fluid administration results in less progression to moderate PPH. Study design In four Dutch hospitals we recruited women of 18 years and over, and more than 24 weeks pregnant. Exclusion criteria were: anticoagulant therapy, known coagulation disorders, pre-eclampsia, antenatal diagnosis of abnormally adhesive placenta, and a contraindication for liberal fluid therapy. We blindly randomized participants at 500 mL and ongoing blood loss in the third stage of labor between restrictive fluid administration (clear fluids 0.75–1.0 times the volume of blood lost) and liberal fluid administration (clear fluids 1.5–2.0 times the volume of blood lost). The primary outcome was progression to more than 1000 mL blood loss. Analyses were according to the intention-to-treat principle. Results From August 2014 till September 2019, 5190 women were informed of whom 1622 agreed to participate. A total of 252 women were randomized of which 130 were assigned to the restrictive group and 122 to the liberal group. In the restrictive management group 51 of the 130 patients (39.2%) progressed to more than 1000 mL blood loss versus 61 of the 119 patients (51.3%) in the liberal management group (difference, -12.0% [95%-CI -24.3% to 0.3%], p = 0.057). There was no difference in the need for blood transfusion, coagulation parameters, or in adverse events between the groups. Conclusions Although a restrictive fluid resuscitation in women with mild PPH could not been proven to be superior, it does not increase the need for blood transfusion, alter coagulation parameters, or cause a rise in adverse events. It can be considered as an alternative treatment option to liberal fluid resuscitation. Trial registration NTR3789.

Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial

2020 ◽  
pp. 27-37
Author(s):  
Suresh Durgam ◽  
Willie Earley ◽  
Rui Li ◽  
Dayong Li ◽  
Kaifeng Lu ◽  
...  
Keyword(s):  
Safety Profile ◽  
Relapse Prevention ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Controlled ◽  
Time To Relapse

Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97 weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3—9 mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9 mg/d) or placebo for double-blind treatment (up to 72 weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n = 99) or cariprazine (n = 101). Time to relapse was significantly longer in cariprazine — versus placebo-treated patients (P = .0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥ 10% of patients during open-label treatment; there were no cariprazine adverse events ≥ 10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060. Key words: schizophrenia; cariprazine; long-term treatment; relapse prevention; randomized controlled trial; oral antipsychotics

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