Dataset Information

Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation.

ABSTRACT: Brain arteriovenous malformations (bAVMs) are relatively rare, although their potential for secondary intracranial haemorrhage (ICH) makes their diagnosis and management essential to the community. Currently, invasive therapies (surgical resection, stereotactic radiosurgery and endovascular embolisation) are the only interventions that offer a reduction in ICH risk. There is no designated medical therapy for bAVM, although there is growing animal and human evidence supporting a role for bevacizumab to reduce the size of AVMs. In this single-arm pilot study, two patients with large bAVMs (deemed unresectable by an interdisciplinary team) received bevacizumab 5 mg/kg every 2 weeks for 12 weeks. Due to limitations of external funding, the intended sample size of 10 participants was not reached. Primary outcome measure was change in bAVM volume from baseline at 26 and 52 weeks. No change in bAVM volume was observed 26 or 52 weeks after bevacizumab treatment. No clinically important adverse events were observed during the 52-week study period. There were no observed instances of ICH. Sera vascular endothelial growth factor levels were reduced at 26 weeks and returned to baseline at 52 weeks. This pilot study is the first to test bevacizumab for patients with bAVMs. Bevacizumab therapy was well tolerated in both subjects. No radiographic changes were observed over the 52-week study period. Subsequent larger clinical trials are in order to assess for dose-dependent efficacy and rarer adverse drug effects. Trial registration number: NCT02314377.

SUBMITTER: Muster R

PROVIDER: S-EPMC8204171 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundMechanical labour induction with a transcervical balloon is as effective as pharmacological methods, with fewer adverse effects. Its use has been limited to labour induction with an unfavourable cervix able to retain the balloon. We have developed an innovative approach using 2-3 balloons side-by-side to extend the benefits of mechanical labour induction/augmentation with a favourable cervix without having to resort to amniotomy or uterotonics.ObjectivesTo assess the effectiveness of side-by-side balloons for extended labour induction/augmentation.MethodsWe conducted a single arm proof of concept trial at Princess Marina Hospital (PMH) in Gaborone, Botswana. Participants were assessed as unsuitable for single balloon labour induction based on a modified Bishop cervical score of 7 or more. Three Foley catheters taped symmetrically side by side were passed through the cervix and inflated with 60mls each. Traction was applied with a weight of 250mls water suspended over the bed-end. The use of uterotonics, time from induction to birth, mode of birth, Apgar scores and adverse maternal and neonatal outcomes were recorded. Participants' satisfaction with the method of labour induction was assessed using a descriptive scale.ResultsWe enrolled 20 participants of whom two were nulliparous. Indications for labour induction were mainly late term (70%) and hypertensive disorders of pregnancy (25%). The mean cervical score was 7.2. Overall, 17 (85%) of the participants achieved a vaginal birth, of whom 5 required oxytocin for labour augmentation. Four of these had requested removal of the balloons, one due to discomfort and three felt the process was taking too long. Three participants underwent caesarean birth. The mean time from initiation of labour induction to vaginal birth was 16 h (standard deviation (SD) 8.4) and 20 h for caesarean birth (SD 10.5). There were no 5-minute Apgar scores below 7 nor neonatal admissions. One baby required brief resuscitation. There were no adverse maternal outcomes.ConclusionThis proof-of-concept study suggests that use of side-by-side balloons in participants with favourable cervix is effective in achieving vaginal birth in most participants without uterotonics or amniotomy. There were no adverse outcomes, though the study was too small to exclude the possibility of rare adverse outcomes. This offers a novel option for labour induction/augmentation, particularly where uterotonics or amniotomy are best avoided such as prior caesarean birth, vertical infection transmission risk and in settings with limited capacity for fetal surveillance. The results clearly justify larger randomized trials to evaluate this novel approach with greater precision. On the basis of the current study we are developing a purpose-designed balloon for extended balloon labour induction.

Project description:IntroductionPersonalised cancer screening aims to improve benefits, reduce harms and being more cost-effective than age-based screening. The objective of the DECIDO study is to assess the acceptability and feasibility of offering risk-based personalised breast cancer screening and its integration in regular clinical practice in a National Health System setting.Methods and analysisThe study is designed as a single-arm proof-of-concept trial. The study sample will include 385 women aged 40-50 years resident in a primary care health area in Spain. The study intervention consists of (1) a baseline visit; (2) breast cancer risk estimation; (3) a second visit for risk communication and screening recommendations based on breast cancer risk and (4) a follow-up to obtain the study outcomes.A polygenic risk score (PRS) will be constructed as a composite likelihood ratio of 83 single nucleotide polymorphisms. The Breast Cancer Surveillance Consortium risk model, including age, race/ethnicity, family history of breast cancer, benign breast disease and breast density will be used to estimate a preliminary 5-year absolute risk of breast cancer. A Bayesian approach will be used to update this risk with the PRS value.The primary outcome measures will be attitude towards, intention to participate in and satisfaction with personalised breast cancer screening. Secondary outcomes will include the proportions of women who accept to participate and who complete the different phases of the study. The exact binomial and the Student's t-test will be used to obtain 95% CIs.Ethics and disseminationThe study protocol was approved by the Drug Research Ethics Committee of the University Hospital Arnau de Vilanova. The trial will be conducted in compliance with this study protocol, the Declaration of Helsinki and Good Clinical Practice.The results will be published in peer-reviewed scientific journals and disseminated in scientific conferences and media.Trial registration numberNCT03791008.

Project description:BackgroundThere is strong rationale for interference with T cell co-stimulation in IgG4-related disease (IgG4-RD), but the literature to evaluate this is limited to a single case report.MethodsWe conducted a ten-subject proof-of-concept trial of abatacept in active IgG4-RD. All subjects met the ACR/EULAR Classification Criteria for IgG4-RD. Subjects received subcutaneous abatacept 125 mg weekly for 24 weeks. Concurrent glucocorticoid treatment was permitted but if used had to be discontinued by week four. The primary endpoint, complete remission at 24 weeks, was defined as an IgG4-RD Responder Index score of 0. Peripheral blood mononuclear cells were collected at baseline, four weeks, and 12 weeks. B and T cell subsets were quantified using a 25-parameter flow cytometry panel.FindingsThe subjects' median age was 68 years; seven subjects were male and nine were Caucasian. Baseline organ involvement was diverse with a median of 5 organs affected at the time of enrollment. The median serum IgG4 concentration was 597 mg/dL (IQR 304-913 mg/dL). Three subjects received concomitant prednisone at baseline. Six subjects (60%) had a disease response by week 12, five of whom maintained this response at week 24. Abatacept was stopped in the remaining five subjects (50%) due to flare (N = 1) or lack of response by week 12 (N = 4). Three subjects (30%) achieved the primary endpoint.Baseline proportions of unswitched memory B cells predicted responsiveness to abatacept. Reductions in serum IgE, circulating plasmablasts, and activated type 2 T follicular helper (TFH2) cells correlated with response to treatment. One adverse event (grade two thrombocytopenia) was attributed to abatacept.InterpretationAbatacept was associated with variable treatment responses in IgG4-RD. Half of the subjects achieved sustained treatment responses to abatacept alone, without glucocorticoids. Correlates of clinical response included reductions in serum IgE, circulating plasmablasts, and activated TFH2 cells. Response to abatacept was predicted by higher proportions of unswitched memory B cells at baseline.

Dataset Information

Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets