Dataset Information

Safety and feasibility of using acellular sterile filtered amniotic fluid as a treatment for patients with COVID-19: protocol for a randomised, double-blinded, placebo-controlled clinical trial.

ABSTRACT:

Introduction

Human amniotic fluid (hAF) has been shown to reduce inflammation in multiple experimental models. hAF has previously been approved by the US Food and Drug Administration (FDA) as a human cellular and tissue product for tissue injury for human administration, and used safely in thousands of patients as a therapeutic treatment for diverse conditions. Given the profound inflammatory response observed in patients with COVID-19, and the successful completion of 10-patient pilot study of intravenous hAF, we present a trial design for a larger clinical trial of intravenous hAF for the treatment of COVID-19.

Methods and analysis

This paper describes the methodology of a phase I/II randomised, double-blinded, placebo-controlled clinical trial to determine the safety and feasibility of using acellular sterile filtered amniotic fluid as a treatment for patients with COVID-19. Primary outcome will be the change in C-reactive protein. Secondary outcomes include safety, biomarker inflammatory levels and clinically relevant outcomes at 30 days, including mortality, ventilator-free days and hospital and intensive care unit length of stay. Exploratory outcomes of health-related quality-of-life patient-reported outcomes will be collected. Hospitalised patients with laboratory-confirmed COVID-19 will be recruited.

Ethics and dissemination

This study was approved by the University of Utah Institutional Review Board (IRB_0013292), approved by the US FDA under Investigational New Drug (No 23369) and is registered on ClinicalTrials.gov. Results will be disseminated via peer-reviewed publications and conference presentations.

Trial registration number

NCT04497389; Pre-results.

SUBMITTER: Tonna JE

PROVIDER: S-EPMC7880092 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Safety and feasibility of using acellular sterile filtered amniotic fluid as a treatment for patients with COVID-19: protocol for a randomised, double-blinded, placebo-controlled clinical trial.

Tonna Joseph E JE Pierce Jan J Hatton Nathan N Lewis Giavonni G Phillips John D JD Messina Alyssa A Skidmore Chloe R CR Taylor Kirsten K Selzman Craig H CH

BMJ open 20210211 2

<h4>Introduction</h4>Human amniotic fluid (hAF) has been shown to reduce inflammation in multiple experimental models. hAF has previously been approved by the US Food and Drug Administration (FDA) as a human cellular and tissue product for tissue injury for human administration, and used safely in thousands of patients as a therapeutic treatment for diverse conditions. Given the profound inflammatory response observed in patients with COVID-19, and the successful completion of 10-patient pilot s ...[more]

PMID: 33574155

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Project description:ImportanceAcellular human amniotic fluid (hAF) is an antimicrobial and anti-inflammatory fluid that has been used to treat various pro-inflammatory conditions. In a feasibility study, we have previously demonstrated that hAF could be safely administered to severely ill patients with coronavirus disease-19 (COVID-19). The impact of acellular hAF on markers of systemic inflammation and clinical outcomes during COVID-19 infection remain unknown.ObjectiveTo determine the safety and efficacy of acellular, sterile processed intravenously administered hAF on markers of systemic inflammation during COVID-19.Design, settings and participantsThis single-center Phase I/II randomized, placebo controlled clinical trial enrolled adult (age ≥ 18 years) patients hospitalized for respiratory symptoms of COVID-19, including hypoxemia, tachypnea or dyspnea. The study was powered for outcomes with an anticipated enrollment of 60 patients. From 09/28/2020 to 02/04/2022 we enrolled and randomized 47 (of an anticipated 60) patients hospitalized due to COVID-19. One patient withdrew consent after randomization but prior to treatment. Safety outcomes to 30 days were collected through hospital discharge and were complete by the end of screening on 6/30/2022.InterventionsIntravenous administration of 10 cc sterile processed acellular hAF once daily for up to 5 days vs placebo.Main outcome and measuresBlood biomarkers of inflammation, including C-Reactive protein (CRP), lactate dehydrogenase, D-dimer, and interleukin-6 (IL-6), as well as safety outcomes.ResultsPatients who were randomized to hAF (n = 23) were no more likely to have improvements in CRP from baseline to Day 6 than patients who were randomized to placebo (n = 24) hAF: -5.9 [IQR -8.2, -0.6] vs placebo: -5.9 [-9.4, -2.05]; p = 0.6077). There were no significant differences in safety outcomes or adverse events. Secondary measures of inflammation including lactate dehydrogenase, D-dimer and IL-6 were not statistically different from baseline to day 6.Conclusions and relevanceIn this randomized clinical trial involving hospitalized patients with COVID-19, the intravenous administration of 10 cc of hAF daily for 5 days did not result in statistically significant differences in either safety or markers of systemic inflammation compared to placebo, though we did not achieve our enrollment target of 60 patients.Trial registrationThis trial was registered at ClinicalTrials.gov as #NCT04497389 on 04/08/2020.

Project description:Osteoarthritic knee (OA knee) is a common condition in the elderly. Exploration of non-invasive complementary therapies for OA knee is warranted given the limitations of pharmacologic therapies. Auriculotherapy (AT) is a therapeutic method in which specific points on the auricle are stimulated to treat various disorders of the body, and the therapeutic value and synergistic effect of laser auriculotherapy (LAT) when combined with magneto-auriculotherapy (MAT) merits further investigation.This study adopted a double-blinded four-arm randomized placebo design. The aims of study are (1) to assess the feasibility of AT among elders with OA knee in a future large-scale study, including the use of blinding in subjects and evaluators, acceptance of treatment protocol, and estimating the effect size and attrition rate; and (2) to evaluate the preliminary effect of AT in elders with OA knee. Subjects were randomly divided into four groups with different modes of AT with/without placebo objects. A total of 43 subjects completed the 6-week intervention and post-assessment. Assessments included a numerical rating scale of pain (NRS), the timed-up-and-go test (TUGT), and standard goniometer measurements during knee flexion and extension, Kruskal-Wallis test was used to evaluate differences among groups, and Wilcoxon sign-ranked test for examining within-group comparison.Preliminary results indicated the absence of differences in the NRS, TUGT, and active/passive knee flexion and extension at baseline, as well as post-therapy, between the four groups. Even though the differences of these parameters between groups were not significant, the relative differences of NRS and TUGT in subjects who received combined MAT plus LAT were higher than those treated with MAT or LAT alone, or the placebo group. Four of the six parameters demonstrated significant within group differences in subjects who received MAT and/or LAT, whereas no significant differences were found in the placebo group.This study demonstrates that the AT protocol adopted in this study for elders with OA knee is feasible and could be applied in future larger-scale study. Larger sample size should be considered in a future trial to determine the causal relationship between treatment and effect.ClinicalTrials.gov: NCT02352636 . Registered on 23 January 2015.

Project description:Postoperative pain control remains a major challenge for surgical procedures, including laparoscopic gastric bypass. Pain management is particularly relevant in obese patients who experience a higher number of cardiovascular and pulmonary events. Effective pain management may reduce their risk of serious postoperative complication, such as deep vein thrombosis and pulmonary emboli. The objective of this study is to evaluate the efficacy of intraperitoneal local anaesthetic, ropivacaine, to reduce postoperative pain in patients undergoing laparoscopic Roux-en-Y gastric bypass.A randomised controlled trial will be conducted to compare intraperitoneal ropivacaine (intervention) versus normal saline (placebo) in 120 adult patients undergoing bariatric bypass surgery. Ropivacaine will be infused over the oesophageal hiatus and throughout the abdomen. Patients in the control arm will undergo the same treatment with normal saline. The primary end point will be postoperative pain at 1, 2 and 4?h postoperatively. Pain measurements will then occur every 4?h for 24?h and every 8?h until discharge. Secondary end points will include opioid use, peak expiratory flow, 6?min walk distance and quality of life assessed in the immediate postoperative period. Intention-to-treat analysis will be used and repeated measures will be analysed using mixed modelling approach. Post-hoc pairwise comparison of the treatment groups at different time points will be carried out using multiple comparisons with adjustment to the type 1 error. Results of the study will inform the feasibility of recruitment and inform sample size of a larger definitive randomised trial to evaluate the effectiveness of intraperitoneal ropivacaine.This study has been approved by the Ottawa Health Science Network Research Ethics Board and Health Canada in April 2014. The findings of the study will be disseminated through national and international conferences and peer-reviewed journals.Clinicaltrial.gov NCT02154763.

Project description:IntroductionA novel coronavirus, designated SARS-CoV-2, caused an international outbreak of a respiratory illness, termed COVID-19 in December 2019. There is a lack of specific therapeutic agents based on evidence for this novel coronavirus infection; however, several medications have been evaluated as a potential therapy. Therapy is required to treat symptomatic patients and decrease the virus carriage duration to limit the communitytransmission.Methods and analysisWe hypothesise that patients with mild COVID-19 treated with favipiravir will have a shorter duration of time to virus clearance than the control group. The primary outcome is to evaluate the effect of favipiravir on the timing of the PCR test conversion from positive to negative within 15 days after starting the medicine.Adults (>18 years, men or nonpregnant women, diagnosed with mild COVID-19 within 5 days of disease onset) are being recruited by physicians participating from the Ministry of National Guard Health Affairs and the Ministry of Health ethics committee approved primary healthcare centres. This double-blind, randomised trial comprises three significant parts: screening, treatment and a follow-up period. The treating physician and patients are blinded. Eligible participants are randomised in a 1:1 ratio to either the therapy group (favipiravir) or a control group (placebo) with 1800 mg by mouth two times per day for the first day, followed by 800 mg two times per day for 4-7 days. Serial nasopharyngeal/oropharyngeal swab samples are obtained on day 1 (5 days before therapy). On day5±1 day, 10±1 day, 15±2 days, extra nasopharyngeal/oropharyngeal PCR COVID-19 samples are requested.The primary analysis population for evaluating both the efficacy and safety outcomes will be a modified intention to treat population. Anticipating a 10% dropout rate, we expect to recruit 288 subjects per arm. The results assume that the hazard ratio is constant throughout the study and that the Cox proportional hazard regression is used to analyse the data.Ethics and disseminationThe study was approved by the King Abdullah International Medical Research Centre Institutional Review Board (28 April 2020) and the Ministry of Health Institutional Review Board (1 July 2020). Protocol details and any amendments will be reported to https://clinicaltrials.gov/ct2/show/NCT04464408. The results will be published in peer-reviewed journals.Trial registration numberNational Clinical Trial Registry (NCT04464408).

Project description:ObjectiveTo distinguish between prostaglandin and prostamide concentrations in the amniotic fluid of women who had an episode of preterm labor with intact membranes through the utilisation of liquid chromatography-tandem mass spectrometry.Study designLiquid chromatography-tandem mass spectrometry analysis of amniotic fluid of women with preterm labor and (1) subsequent delivery at term (2) preterm delivery without intra-amniotic inflammation; (3) preterm delivery with sterile intra-amniotic inflammation (interleukin (IL)-6>2.6 ng/mL without detectable microorganisms); and (4) preterm delivery with intra-amniotic infection [IL-6>2.6 ng/mL with detectable microorganisms].Results(1) amniotic fluid concentrations of PGE2, PGF2α, and PGFM were higher in patients with intra-amniotic infection than in those without intra-amniotic inflammation; (2) PGE2 and PGF2α concentrations were also greater in patients with intra-amniotic infection than in those with sterile intra-amniotic inflammation; (3) patients with sterile intra-amniotic inflammation had higher amniotic fluid concentrations of PGE2 and PGFM than those without intra-amniotic inflammation who delivered at term; (4) PGFM concentrations were also greater in women with sterile intra-amniotic inflammation than in those without intra-amniotic inflammation who delivered preterm; (5) amniotic fluid concentrations of prostamides (PGE2-EA and PGF2α-EA) were not different among patients with preterm labor; (6) amniotic fluid concentrations of prostaglandins, but no prostamides, were higher in cases with intra-amniotic inflammation; and (7) the PGE2:PGE2-EA and PGF2α:PGF2α-EA ratios were higher in patients with intra-amniotic infection compared to those without inflammation.ConclusionsMass spectrometric analysis of amniotic fluid indicated that amniotic fluid concentrations of prostaglandins, but no prostamides, were higher in women with preterm labor and intra-amniotic infection than in other patients with an episode of preterm labor. Yet, women with intra-amniotic infection had greater amniotic fluid concentrations of PGE2 and PGF2α than those with sterile intra-amniotic inflammation, suggesting that these two clinical conditions may be differentiated by using mass spectrometric analysis of amniotic fluid.

Dataset Information

Safety and feasibility of using acellular sterile filtered amniotic fluid as a treatment for patients with COVID-19: protocol for a randomised, double-blinded, placebo-controlled clinical trial.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Safety and feasibility of using acellular sterile filtered amniotic fluid as a treatment for patients with COVID-19: protocol for a randomised, double-blinded, placebo-controlled clinical trial.

Similar Datasets

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