Clinical-Trial Investigators’ Assessment of Serious Adverse Events Before and After Unblinding of Suspected Unexpected Serious Adverse Reactions (SUSARs)

Drug Safety ◽  
2007 ◽  
Vol 30 (10) ◽  
pp. 919-990
Author(s):  
T J Dyszynski ◽  
E R Arens ◽  
R Fescharek
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Adverse Reactions ◽  
Serious Adverse Events ◽  
Before And After

scholarly journals ACTR-18. A PHASE IB/II CLINICAL TRIAL OF DODECAFLUOROPENTANE EMULSION (DDFPE) AS A RADIOSENSITIZER IN GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi16-vi16 ◽  
Author(s):  
Jason Lickliter ◽  
Jeremy Ruben ◽  
Ross Jennens ◽  
Ganessan Kichenadasse ◽  
Cecelia Gzell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Adverse Events ◽  
Tumor Hypoxia ◽  
Standard Of Care ◽  
Supplemental Oxygen ◽  
Tumor Oxygenation ◽  
Serious Adverse Events ◽  
Before And After ◽  
Mri Scans

Abstract BACKGROUND Tumor hypoxia decreases the response of glioblastoma multiforme (GBM) to radiotherapy (RT) and chemotherapy (temozolomide[TMZ]). The purpose of this study was to evaluate the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM and stratify the results based on predicted TMZ response. METHODS With ethics approval and informed consent, 11 adult GBM patients were enrolled. Patients were administered DDFPe via IV infusion (2% w/vol at doses of 0.05, 0.1 or 0.17 mL/kg) within 5–30 minutes prior to each 2 Gy fraction of RT (30 fractions over 6-weeks) while breathing supplemental oxygen. Patients also received standard concurrent and adjuvant TMZ. To evaluate the reversal of tumor hypoxia, patients underwent oxygen-sensitive (TOLD) MRI before and after DDFPe administration. Patients were also studied with serial MRI scans per standard of care and followed for survival. RESULTS The non-serious adverse events considered by the investigator to be possibly, probably, or definitely related to DDFPe administration included fatigue (n=4), headache (n=2) and decrease in platelet count (n=2). Serious adverse events included two patients with symptomatic radiation necrosis: one patient at each of dose levels 0.1 and 0.17 mL/kg. Enrollment continued at the 0.1 mL/kg dose without additional significant DDFPe-related toxicity. Historically, the average overall survival for GBM patients is about 14.6 months. The median overall survival for the study was 591 days, or 19.4 months. According to independent review of the serial MR images, the median time to progression was 555 days, or 18 months, compared to a historical control of 6.9 months. TOLD MRI showed a trend in improved tumor oxygenation. CONCLUSION Although small, this trial shows that DDFPe used as a radiosensitizer appears to be safe and may provide some survival benefit. The FDA has allowed a Phase II clinical trial to assess its effectiveness.

scholarly journals Safety and Immunogenicity of Tetanus-Diphtheria-Acellular Pertussis Vaccine Administered to Children 10 or 11 Years of Age

2014 ◽  
Vol 21 (11) ◽  
pp. 1560-1564 ◽  
Author(s):  
Gary S. Marshall ◽  
Vitali Pool ◽  
David P. Greenberg ◽  
David R. Johnson ◽  
Xiaohua Sheng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Injection Site ◽  
Adverse Reactions ◽  
Geometric Mean ◽  
Serious Adverse Events ◽  
Intramuscular Dose ◽  
Injection Site Reactions ◽  
Systemic Reactions ◽  
Pertussis Antigens

ABSTRACTBoosting immunity to tetanus, diphtheria, and pertussis through the use of Tdap vaccines is routinely recommended at 11 to 12 years of age; some states, however, require Tdap for entry into middle school, which may begin at 10 years of age. This study was conducted to determine whether Tdap5 (Adacel), which is licensed for use in children beginning at 11 years of age, is as safe and immunogenic in 10-year-olds as it is in 11-year-olds. Children who had received 5 previous doses of any diphtheria-tetanus-acellular pertussis (DTaP) vaccine were enrolled in a phase IV clinical trial; 646 10-year-olds and 645 11-year-olds completed the study, which involved a single intramuscular dose of Tdap5 along with pre- and postvaccination serologies. Postvaccination geometric mean concentrations (GMCs) of antibody to pertussis antigens (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbria types 2 and 3) of 10-year-olds were noninferior to those of 11-year-olds, as were booster response rates for all pertussis antibodies, except for those to fimbrial antigens (94% and 97%, respectively). Seroprotection rates among 10-year-olds for tetanus and diphtheria were noninferior to those in 11-year-olds. Rates of injection site reactions, solicited systemic reactions, and unsolicited adverse events, adverse reactions, and serious adverse events were similar in the two groups. These data support the conclusion that Tdap5 is safe and immunogenic in 10-year-olds. (This study has been registered at ClinicalTrials.gov under registration no. NCT01311557.)

scholarly journals Safety of meningococcal group B vaccination in hospitalised premature infants

2018 ◽  
Vol 104 (2) ◽  
pp. F171-F175 ◽  
Author(s):  
Alison Kent ◽  
Kazim Beebeejaun ◽  
Serena Braccio ◽  
Seilesh Kadambari ◽  
Paul Clarke ◽  
...  
Keyword(s):  
Adverse Events ◽  
Premature Infants ◽  
Antibiotic Use ◽  
Neurological Status ◽  
Serious Adverse Events ◽  
Historical Cohort ◽  
Protein Levels ◽  
Reactive Protein ◽  
Before And After ◽  
Group B

ObjectivesTo assess the risk of significant adverse events in premature infants receiving the novel 4-component group B meningococcal vaccine (4CMenB) with their routine immunisations at 2 months of age.Participants, design and settingIn December 2015, Public Health England requested neonatal units across England to voluntarily participate in a national audit; 19 units agreed to participate. Anonymised questionnaires were completed for infants receiving 4CMenB alongside their routine immunisations. For comparison, a historical cohort of premature infants receiving their primary immunisations without 4CMenB or paracetamol prophylaxis was used.Main outcome measuresParacetamol use; temperature, cardiovascular, respiratory and neurological status before and after vaccination; and management and investigations postvaccination, including serum C reactive protein levels, infection screens and antibiotic use.ResultsComplete questionnaires were returned for 133 premature infants (<35 weeks’ gestation) who received their first dose of 4CMenB at 8 weeks of age, including 108 who received prophylactic paracetamol according to national recommendations. Overall, 7% (8/108) of infants receiving 4CMenB with paracetamol had fever (>38°C) after vaccination compared with 20% (5/25) of those receiving 4CMenB without paracetamol (P=0.06) and none of those in the historical cohort. There were no significant differences between cohorts in the proportion of infants with apnoea, bradycardia, desaturation and receiving respiratory support after vaccination.Conclusions4CMenB does not increase the risk of serious adverse events in hospitalised premature infants. This audit supports the current national recommendations to offer 4CMenB with other routine vaccinations and prophylactic paracetamol to premature infants at their chronological age.

scholarly journals A Pilot Placebo Controlled Randomized Trial of Dexamethasone for Chronic Subdural Hematoma

2016 ◽  
Vol 43 (2) ◽  
pp. 284-290 ◽  
Author(s):  
Michel Prud’homme ◽  
François Mathieu ◽  
Nicolas Marcotte ◽  
Sylvine Cottin
Keyword(s):  
Conservative Treatment ◽  
Adverse Events ◽  
Small Sample Size ◽  
Chronic Subdural Hematoma ◽  
Symptomatic Patient ◽  
Placebo Treatment ◽  
Small Sample ◽  
Chi Square ◽  
Serious Adverse Events ◽  
Before And After

AbstractBackground: Current opinions regarding the use of dexamethasone in the treatment of chronic subdural hematomas (CSDH) are only based on observational studies. Moreover, the use of corticosteroids in asymptomatic or minimally symptomatic patient with this condition remains controversial. Here, we present data from a prospective randomized pilot study of CSDH patients treated with dexamethasone or placebo. Methods: Twenty patients with imaging-confirmed CSDH were recruited from a single center and randomized to receive dexamethasone (12 mg/day for 3 weeks followed by tapering) or placebo as a conservative treatment. Patients were followed for 6 months and the rate of success of conservative treatment with dexamethasone versus placebo was measured. Parameters such as hematoma thickness and clinical changes were also compared before and after treatment with chi-square tests. Adverse events and complications were documented. Results: During the 6-month follow-up, one of ten patients treated with corticosteroids had to undergo surgical drainage and three of ten patients were treated surgically after placebo treatment. At the end of the study, all remaining patients had complete radiological resolution. No significant differences were observed in terms of hematoma thickness profile and impression of change; however, patients experienced more severe side effects when treated with steroids as compared with placebo. Dexamethasone contributed to many serious adverse events. Conclusions: Given the small sample size, these preliminary results have not shown a clear beneficial effect of dexamethasone against placebo in our patients. However, the number of secondary effects reported was much greater for corticosteroids, and dexamethasone treatment was responsible for significant complications.

scholarly journals Apheresis-Adverse Events in Man and Machine Individualities

2020 ◽  
Vol 14 (1) ◽  
pp. 27-30
Author(s):  
Md Ashraful Hoque ◽  
Kashfia Islam ◽  
Selina Akter
Keyword(s):  
Adverse Reaction ◽  
Adverse Events ◽  
Adverse Reactions ◽  
Key Factors ◽  
Serious Adverse Events ◽  
Female Ratio ◽  
The Mean ◽  
Male To Female ◽  
Citrate Toxicity ◽  
Common Adverse Reaction

Adverse events due to platelet pheresis are not unheard of citrate related reactions being the most common. Most of these events are mild and self limiting. The current study describes adverse events in platelet pheresis using modern apheresis systems. This prospective study included 1455 platelet pheresis procedures done from July 2016 to December 2017. Procedures were performed on Hemonetics MCS+, Trima Accel and Cobe spectra cell separators. The endpoint of each procedure was a yield of 3 × 1011 platelets (PLTs) per unit. Donor adverse reaction if any was managed, reported, and documented. The median age of donors was 31 years with male to female ratio of 13:1. The median body surface area and body mass index were 1.64 m2 and 22.4 kg/m2, respectively. The mean PLT count of donors was 199.8 × 103/uL with a mean hemoglobin value of 13.6 g/dl. ACD infusion was significantly more in the Hemonetics MCS+, (P< 0.01). Donation time was least with the Trima compared to Hemonetics MCS+ (P< 0.01) and Cobe (P< 0.001). Total whole blood volume processed was higher in Hemonetics MCS+, (P< 0.01). Paresthesia due to citrate toxicity was the most common adverse reaction (65.3%), and vascular injury was observed in only five donors. The overall incidence of adverse reaction was 3.4%. Serious adverse events were not observed. The modern generation apheresis machines are more donors friendly and cause less adverse reactions compared to the older versions. Good donor screening, optimized donor physiognomic and hematological values and skilled operators are the key factors in reaction reduction by apheresis. Faridpur Med. Coll. J. Jan 2019;14(1): 27-30

Results of the ADRRAD Trial of pelvic IMRT plus radium-223 in men with mHSPC metastatic to bone.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 136-136
Author(s):  
Joe O'Sullivan ◽  
Philip Geoffrey Turner ◽  
Suneil Jain ◽  
Arthur Grey ◽  
Sandra Biggart ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase 1 ◽  
Palliative Radiotherapy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Pelvic Radiotherapy ◽  
Serious Adverse Events ◽  
Radium 223

136 Background: Radiotherapy to the Prostate in mHSPC improves overall survival (OS) and Progression free survival (PFS) for patients with low-volume-disease[1]. Radium-223 in metastatic castration resistant prostate cancer (mCRPC) improves OS [2]. We conducted a prospective phase 1/2 clinical trial in mHSPC, testing the combination of with LHRHa, concurrent pelvic radiotherapy and radium-223. Methods: Thirty patients were recruited with mHSPC; they had a minimum of 3 bone metastases (majority had > 20 bone mets), nil visceral metastases, PS0-1. Patients were encouraged to receive up front docetaxel. They were treated with ongoing LHRHa, pelvic radiotherapy aiming for 74Gy in 37 fractions to prostate PTV with 60Gy concomitantly delivered to pelvic nodal PTV. Concurrently, patients received radium-223, 55kBq/kg for 6 cycles q28 days; fraction 1 radiotherapy was synchronous with cycle 1 day 1 radium-223. Results: Median age was 63 years and 28 (93%) received at least 4 cycles of docetaxel. One patient received prostate only radiotherapy due to bowel constraints. Three patients had cycle 6 radium-223 omitted. At a median follow-up of 28 months, there have been 415 Adverse events, (3% Grade >3), and 6 serious adverse events (SAEs) ( 2 episodes of UTI, 1 each of cystitis non-infective, cardiac chest pain, pyrexia and AKI). Commonest AEs by number were: leucopenia, neutropenia, and diarrhoea. Ten SSE’s have occurred including 8 courses of palliative radiotherapy for bone pain, 1 course of radiotherapy for impending MSCC and 1 pathological fracture. At median follow up 28.0 months, median biochemical PFS is 17.9 months, median OS not yet reached. Conclusions: This trial shows clear tolerability and promising early efficacy data requiring further exploration in a randomised phase 3 trial. Clinical trial information: 2014-000273-39.

scholarly journals P615 Safety of vedolizumab in the treatment of IBD in a single tertiary centre

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S511-S513
Author(s):  
G Peruzzi ◽  
L Calandrini ◽  
H Privitera Hrustemovic ◽  
M Salice ◽  
A Decorato ◽  
...  
Keyword(s):  
Adverse Events ◽  
Anaphylactic Shock ◽  
Adverse Reactions ◽  
Disease Onset ◽  
Perianal Disease ◽  
Uncontrolled Hypertension ◽  
Drug Discontinuation ◽  
Real World Data ◽  
Serious Adverse Events ◽  
Cutaneous Manifestations

Abstract Background There is a lot of data on Vedolizumab efficacy in the treatment of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD). Despite this, we have little real-world data on its adverse reactions. We aimed to identify and quantify principal adverse reactions in order to assess the safety of the drug. Methods UC and CD patients from a single tertiary IBD referral centre receiving Vedolizumab treatment between September 2016 and August 2019 were included. Data were collected prospectively at week 22, 54 and 108. Adverse events were categorised as infections, rheumatic/cutaneous disorders, allergy-related symptoms/anaphylactic shock, serious adverse events and drug discontinuation. Serious adverse events were those that resulted in hospitalisation or death. Discontinuation was due to drug-related effects or IBD complications that persisted despite the treatment or that could be worsened by drug-induced immunodepression. Results Our analysis comprised 200 patients (86 with UC and 114 with CD: 22% female; median age 58,3 years). Adverse effects were reported in 59/200 (29,5%) patients, leading to treatment discontinuation in 21/200 (10,5%) cases: 2 with UC and 19 with CD. Six patients experienced more the one adverse reaction for a total of 69. Rheumatic disorders were observed in 17/69 (24,6%), infections in 17/69 (24,6%) and cutaneous manifestations in 6/69 (8,7%). One patient complained of headache and another subocclusive symptom. One patient had an asymptomatic increase in cholestasis tests. No anaphylactic shock or allergy-related symptoms were reported while 6 patients (6/69, 8,7%) required hospitalisation (especially for infective complications). Vedolizumab discontinuation was due to perianal disease onset or relapse (9/21, 42,8%), infections (6/21, 28,6%) and rheumatic disorders (5/21, 23,8%); in one case we observed uncontrolled hypertension and Ménière syndrome. Treatment was restarted after surgical management and treatment with antibiotics in 3 patients with perianal disease and 1 with community-acquired pneumonia, respectively. Conclusion In our experience, Vedolizumab is a well-tolerated drug. Most of the adverse events that occurred in our centre were mild and did not require hospitalisation. In some patients discontinuation was not permanent: we performed it in order to treat the condition that contraindicated the administration and restart treatment.

scholarly journals Efficacy and Safety of Tongning Gel for Knee Osteoarthritis: A Multicentre, Randomized, Double-Blinded, Parallel, Placebo-Controlled, Clinical Trial

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ye Zhao ◽  
Zhi Bi Shen ◽  
Ji Rong Ge ◽  
Wen Gang Liu ◽  
Jun Xing Yang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Knee Osteoarthritis ◽  
Physical Function ◽  
Pain Score ◽  
Adverse Reactions ◽  
Control Group ◽  
Womac Pain ◽  
Womac Pain Score ◽  
Experimental Group

Objective. To evaluate the efficacy and safety of Tongning Gel (TNG) compared to placebo-controlled (PC) for knee osteoarthritis (KOA). Methods. A multicentre, randomized, double-blinded, parallel, placebo-controlled, clinical trial was performed in 576 patients (432 patients in the TNG group, 144 patients in the PC group), and 1 in the experimental group withdrew due to nonuse of drug. Patients were randomized to receive TNG or PC applied to knee skin at 3g per time, 2 times per day, which lasted for 3 weeks. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was used to evaluate the primary efficacy of TNG and WOMAC stiffness and physical function and total scores were used to evaluate the secondary efficacy of TNG. All participants who received at least one dose of study drug were included in the safety analysis. This trial has been registered in Chinese Clinical Trial Registry (no. CTR20131276). Results. Primary efficiency outcome: there were significant differences in the decreased value of WOMAC pain score between two groups (P<0.05), and the decreased value of WOMAC pain score in the TNG group were better than those in the PC group (P<0.05). Secondary efficiency outcome: the WOMAC total score, WOMAC stiffness score, WOMAC physical function score, and the decrease of the above indexes of the two groups of patients after treatment were statistically significant (P<0.05), and the improvement of the above indexes in the TNG group was better than that of the PC group (P<0.05). Safety Evaluation. A total of 42 adverse events were reported by 29 patients: 25 adverse events reported by 16 patients (3.71%) in the experimental group and 17 adverse events were reported by 13 patients (9.03%) in the control group. And 8 adverse reactions were reported by 6 patients including 2 adverse reactions by 2 patients (0.46%) in the experimental group and 6 adverse reactions by 4 patients (2.78%) in the control group. Two cases of significant adverse events occurred in the experimental group. Both groups had one serious adverse event, respectively, which were not relevant to the intervention. Conclusion. These results of the trial demonstrate that TNG is superior to placebo in the treatment of patients with KOA, and TNG can improve other symptoms of KOA, such as stiffness and physical function. TNG is safe for the treatment of knee osteoarthritis as a whole.

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