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Abstract Aims Delay of progression from paroxysmal to persistent atrial fibrillation AF is an important measure of long-term success of AF treatment.
Methods This prospective, randomized, controlled, two-arm, open-label trial was conducted at 29 hospitals and medical centres across 13 countries. Conclusions Radiofrequency ablation is superior to guideline-directed AAD therapy in delaying the progression from paroxysmal to persistent AF.
Keywords: Persistent atrial fibrillation, Atrial tachycardia, Antiarrhythmic drugs, Radiofrequency ablation, Progression. Graphical Abstract. Open in a separate window. Introduction Progression from paroxysmal to persistent atrial fibrillation AF results in an increased risk of myocardial infarction, thromboembolism, acute decompensation of heart failure, and stroke 1 , 2 ; delay of progression is therefore an important measure of cardiovascular treatment outcome.
Methods Trial design and study participants ATTEST was a prospective, multicentre, randomized, controlled, two-arm open-label trial performed at 29 sites worldwide Supplementary material online , Appendix between 13 February and 29 May ClinicalTrials. Consent The protocol, amendments, and informed consent forms were reviewed and approved by ethics committees at each individual centre and local authorities as needed.
Figure 1. Table 1 Baseline patient characteristics ITT population. Intervention and treatment The most commonly used catheters during the index ablation procedure were 6-hole irrigated non-CF catheters Figure 2. Sensitivity analyses Sensitivity analyses of the primary endpoint in the PP and as-treated populations as well as in the ITT population using the Heart Rhythm Society expert consensus definition of persistent AF confirmed the above findings. Factors associated with atrial fibrillation progression Using a Cox model with multiple baseline covariates and treatment as the time-dependent covariate in the PP population, treatment modality was significantly associated with AF progression.
Figure 3. Discussion This study demonstrated that RF catheter ablation—as part of standard-of-care AF management including AADs—is superior to guideline-directed AAD therapy alone in delaying the progression to persistent AF in patients with drug-refractory, recurrent paroxysmal AF. Limitations Only RF catheters were used in the current study. Conclusions This multicentre, randomized, controlled study demonstrated that, in patients with drug-refractory paroxysmal AF, standard-of-care RF ablation was superior to rhythm or rate control drug therapy in delaying progression to persistent AF.
Supplementary material Supplementary material is available at Europace online. Funding This work was supported by Biosense Webster, Inc. References 1. Distribution and risk profile of paroxysmal, persistent, and permanent atrial fibrillation in routine clinical practice: insight from the real-life global survey evaluating patients with atrial fibrillation international registry. BRESSO, JULY 12th — EryDel SpA, a global late-stage biotech company aimed at developing and commercializing therapies for the treatment of rare diseases delivered by its proprietary red blood cell technology announced today topline results from its Phase 3 ATTeST clinical trial in patients with Ataxia Telangiectasia AT , a devastating neurological disease for which there is no approved therapy.
The treatment duration was 6 months for the efficacy and extended to 12 months for long term safety assessment. Clinical trial participation is most successful when the protocol is carefully followed and there is frequent contact with the study staff. There are risks, discomforts, and inconveniences associated with any clinical trial. You may have side effects from taking the investigational drug. Side effects are any undesired actions or effects of the investigational drug or treatment.
Potential side effects will be discussed with you during the informed consent process; however, all of the risks associated with taking the investigational drug may not currently be known. Throughout the clinical trial you will be checked by the study team for side effects and it is very important that you tell the study doctor or nurse of any side effects that you have.
Investigational drugs must be evaluated for both immediate and long-term side effects. A participant can leave a clinical trial at any time. When withdrawing from the trial, the participant should let the research team know about it, and the reasons for leaving the study. A control is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug, while the control group is given either a standard treatment for the illness or a placebo.
This study is for research purposes only. It is possible that the symptoms your child experiences from A-T may improve because he or she is taking part in this study, but there is no guarantee that they will benefit in any way.
By participating in this study, you or your child may help gather information on the effectiveness, safety, and tolerability of the study drug, which may also help other patients in the future. After 12 months, you or your child may be offered an opportunity to participate in an additional extension study if they meet the criteria.
During this extension study, they will continue to receive the active study drug. You will be informed in a timely manner if information becomes available that might influence your willingness to continue participating in this study.
However, some went on receiving the drug under a compassionate treatment protocol and are still being treated with EDS today. As described in a recent publication by Leuzzi et al. Their clinical outcome was compared with that of 7 age -matched patients who stopped the treatment after the first 6 infusions IEDAT study. Patients in the extended study experienced a continuous neurological improvement with respect to their pretreatment status, whereas controls showed a progressive neurological deterioration in accordance with the natural course of the disease after the discontinuation of the treatment.
The delivery system used proved to be safe and well-tolerated, and none of the side effects usually associated with the chronic administration of corticosteroids were observed during the entire trial. As suggested by the authors, t hese promising preliminary results call for a large-scale, controlled study looking at the extended treatment of patients with A-T with dexamethasone-loaded red blood cells.
The drug should improve the neurological symptoms of the disease, general quality of life and adaptive behavior. Other statistically significant benefits of the EDS treatment were also seen in secondary measures, such as kinetic function movement , quality of life, adaptive behavior and eye movements. The study drug was generally well tolerated in this subject population, with only two patients discontinuing prematurely due to adverse events.
More details can be found in the paper by Chessa et a l. The EDS procedure ensures that after a rapid, short-lived peak, the drug is released at low and slowly-declining concentrations over the course of approximately 4 weeks. This is different from the daily administration of systemic steroids, which has to be done at higher doses. Dexamethasone is also more effective in penetrating the central nervous system than other steroids such as prednisolone.
These factors suggest that this method of administration may be associated with beneficial effects without the risk of steroid side effects. Following completion of 6 months in the study, all patients who complete the designated procedures and tests will be eligible to continue in an additional 6-month study, to collect information on the long-term safety and benefits of the study drug.
Patients who were originally assigned to receive the study drug will continue on same treatment, while patients on placebo will be progressively shifted to the study drug. In order to determine whether the study drug improves the neurological symptoms of A-T it is necessary to compare the results in participants receiving EDS with those in participants who are receiving a placebo.
However, following completion of 6 months in the study, all patients who complete the designated procedures and tests will be eligible to continue in an additional 6-month study to collect information on the long-term safety and benefits of the study drug. Patients originally randomized to receive the study drug will continue on the same treatment, while patients on placebo will be progressively shifted to the study drug.
At the completion of 12 months in the study, all patients will be receiving the study drug. Each patient who has completed one year in the study will have the option to continue receiving the study drug as part of a separate, on-going study. More complete inclusion and exclusion criteria are available at www. Potential participants must:. Consent forms are legal documents that can only be signed by adults, and assent forms give minors i.
The decision as to whether a patient is eligible for the study is ultimately made by the principal investigator and the study team at the study site. The team can also help each patient and family consider the possible risks and benefits to them. Participants must be at least 6 years of age. Providing that the person meets all other criteria, there is no upper age limit. The patient may be in this research study for up to 13 months including the initial screening visit.
The patient will be asked to visit the study site at least 16 times over this month period. If needed, the study doctor may ask patients to come to the study site for additional visits. Placebo-controlled trials are necessary to establish the benefits and risks of treatments. Patients who are randomized to receive the placebo will receive the EDS procedure without the investigational drug, dexamethasone. During the day screening period which is considered a washout period from previous treatments , any previous treatments with other corticosteroid drugs will be withdrawn.
Other restrictions may also apply. More details will be provided by the study team at the site. Unfortunately, we will not be able to include every patient immediately in this trial, and for that we are truly sorry. However, we are committed to completing the Phase 3 trial as quickly as possible so that if EDS proves to be safe and effective, it can be made available to the A-T community in the shortest period of time.
We know that each decision made about our clinical program impacts patients and families around the world. However our overriding aim is to learn definitively and as quickly as possible whether or not EDS is a safe and effective treatment option for people with A-T. The study drug, administered through the EDS, is an approved drug and is available by prescription for treating a number of chronic long-term inflammatory diseases. Patients with these diseases have to take large doses of the drug orally or by injection for long periods of time and this can result in serious side effects.
A list of most common side effects of the study drug will be found in the study informed consent form. In the course of clinical studies conducted in Europe and the United States, the EDS has been used to give the study drug to human subjects. Over infusions prepared using the EDS have been given to those participating in these studies, with some having received the treatment over two years. No toxicity related to the administration of the study drug using the EDS has been reported.
However, because the EDS is a new method of delivering the study drug, all its side effects may not be known.
You must tell the study staff about any side effects that your child develops. Every clinical trial must be approved and monitored by an Institutional Review Board IRB or Ethics Committee EC to make sure the risks are as low as possible and are worth any potential benefits.
An IRB or EC is an independent committee of physicians, statisticians, community advocates and others that ensures that a clinical trial is ethical and that the rights of study participants are protected. The ethical and legal codes that govern medical practice also apply to clinical trials. In addition, most clinical research is regulated by the government with built-in safeguards to protect the participants.
The trial follows a carefully controlled protocol, a study plan which details what researchers will do in the study. As a clinical trial progresses, researchers report the results of the trial at scientific meetings, to medical journals, and to various government agencies.
This Board is composed of four independent experts who will periodically monitor the safety results and will be able to stop the trial if any safety concerns are detected. J Am Coll Cardiol ;— Hypothesis: Activation of the prevention and termination therapies would reduce the burden and frequency of atrial tachyarrhythmias. Principal Findings: Detection was confirmed in
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