Personalized Antihypertensive Treatment Optimization With Smartphone-Enabled Remote Precision Dosing of Amlodipine During the COVID-19 Pandemic (PERSONAL-CovidBP Trial).

BACKGROUND: The objective of the PERSONAL-CovidBP (Personalised Electronic Record Supported Optimisation When Alone for Patients With Hypertension: Pilot Study for Remote Medical Management of Hypertension During the COVID-19 Pandemic) trial was to assess the efficacy and safety of smartphone-enabled remote precision dosing of amlodipine to control blood pressure (BP) in participants with primary hypertension during the COVID-19 pandemic. METHODS AND RESULTS: This was an open-label, remote, dose titration trial using daily home self-monitoring of BP, drug dose, and side effects with linked smartphone app and telemonitoring. Participants aged ≥18 years with uncontrolled hypertension (5-7 day baseline mean ≥135 mm Hg systolic BP or ≥85 mm Hg diastolic BP) received personalized amlodipine dose titration using novel (1, 2, 3, 4, 6, 7, 8, 9 mg) and standard (5 and 10 mg) doses daily over 14 weeks. The primary outcome of the trial was mean change in systolic BP from baseline to end of treatment. A total of 205 participants were enrolled and mean BP fell from 142/87 (systolic BP/diastolic BP) to 131/81 mm Hg (a reduction of 11 (95% CI, 10-12)/7 (95% CI, 6-7) mm Hg, P<0.001). The majority of participants achieved BP control on novel doses (84%); of those participants, 35% were controlled by 1 mg daily. The majority (88%) controlled on novel doses had no peripheral edema. Adherence to BP recording and reported adherence to medication was 84% and 94%, respectively. Patient retention was 96% (196/205). Treatment was well tolerated with no withdrawals from adverse events. CONCLUSIONS: Personalized dose titration with amlodipine was safe, well tolerated, and efficacious in treating primary hypertension. The majority of participants achieved BP control on novel doses, and with personalization of dose there were no trial discontinuations due to drug intolerance. App-assisted remote clinician dose titration may better balance BP control and adverse effects and help optimize long-term care. REGISTRATION: URL: clinicaltrials.gov. Identifier: NCT04559074.

Feasibility of double-blinded, placebo-controlled interventional study for assessing catheter ablation efficacy in persistent atrial fibrillation: Insights from the ORBITA AF feasibility study.

BACKGROUND: To date, there are no randomized, double-blinded clinical trials comparing catheter ablation to DC cardioversion (DCCV) with medical therapy in patients with persistent atrial fibrillation (PersAF). Conducting a large-scale trial to address this question presents considerable challenges, including recruitment, blinding, and implementation. We conducted a pilot study to evaluate the feasibility of conducting a definitive placebo-controlled trial. METHODS: This prospective trial was carried out at Barts Heart Centre, United Kingdom, employing a randomized, double-blinded, placebo-controlled design. Twenty patients with PersAF (duration <2 years) were recruited, representing 10% of the proposed larger trial as determined by a power calculation. The patients were randomized in a 1:1 ratio to receive either PVI ± DCCV (PVI group) or DCCV + Placebo (DCCV group). The primary endpoint of this feasibility study was to evaluate patient blinding. Patients remained unaware of their treatment allocation until end of study. RESULTS: During the study, 35% of patients experienced recurrence of PersAF prior to completion of 12 months follow-up. Blinding was successfully maintained amongst both patients and medical staff. The DCCV group had a trend to higher recurrence and repeat procedure rate compared to the PVI group (recurrence of PersAF 60% vs 30%; p = .07 and repeat procedure 70% vs 40%; p = .4). The quality of life experienced by individuals in the PVI group showed improvement, as evidenced by enhanced scores on the AF specific questionnaire (AF PROMS) (3 [±4] vs 21 [±8]) and SF-12 mental-component raw score (51.4 [±7] vs 43.24 [±15]) in patients who maintained sinus rhythm at 12 months. CONCLUSION: This feasibility study establishes the potential for conducting a blinded, placebo-controlled trial to evaluate the efficacy of PVI versus DCCV in patients with PersAF.

Sub30: Protocol for the Sub30 feasibility study of a pre-hospital Extracorporeal membrane oxygenation (ECMO) capable advanced resuscitation team at achieving blood flow within 30 ​min in patients with refractory out-of-hospital cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest carries a poor prognosis with survival less than 10% in many patient cohorts. Survival is inversely associated with duration of resuscitation as external chest compressions do not provide sufficient blood flow to prevent irreversible organ damage during a prolonged resuscitation. Extracorporeal membrane oxygenation (ECMO) instituted during cardiac arrest can provide normal physiological blood flows and is termed Extracorporeal Cardio-Pulmonary Resuscitation (ECPR). ECPR may improve survival when used with in-hospital cardiac arrests. This possible survival benefit has not been replicated in trials of out-of-hospital cardiac arrests, possibly because of the additional time it takes to transport the patient to hospital and initiate ECPR. Pre-hospital ECPR may shorten the time between cardiac arrest and physiological blood flows, potentially improving survival. It may also mitigate some of the neurological injury that many survivors suffer. METHODS: Sub30 is a prospective six patient feasibility study. The primary aim is to test whether it is possible to institute ECPR within 30 ​min of collapse in adult patients with refractory out of hospital cardiac arrest (OHCA). The secondary aims are to gather preliminary data on clinical outcomes, resource utilisation, and health economics associated with rapid ECPR delivery in order to plan any subsequent clinical investigation or clinical service. On study days a dedicated fast-response vehicle with ECPR capability will be tasked to out-of-hospital cardiac arrests in an area of London served by Barts Heart Centre. If patients suffer a cardiac arrest refractory to standard advanced resuscitation and meet eligibility criteria, ECPR will be started in the pre-hospital environment. DISCUSSION: Delivering pre-hospital ECPR within 30 ​min of an out-of-hospital cardiac arrest presents significant ethical, clinical, governance and logistical challenges. Prior to conducting an efficacy study of ECPR the feasibility of timely and safe application must be demonstrated first. Extensive planning, multiple high-fidelity multiagency simulations and a unique collaboration between pre-hospital and in-hospital institutions will allow us to test the feasibility of this intervention in London. The study has been reviewed, refined and endorsed by the International ECMO Network (ECMONet). TRIAL REGISTRATION: Clinicaltrials. gov NCT03700125, prospectively registered October 9, 2018.

A pragmatic pilot phase II randomised controlled trial of prothrombin complex concentrates (PCC) versus fresh frozen plasma (FFP) in adult patients who are undergoing heart surgery (PROPHESY).

BACKGROUND: Fresh frozen plasma (FFP) is the accepted standard treatment for clotting factor replacement in bleeding patients during or immediately after cardiac surgery. In the United Kingdom prothrombin complex concentrate (PCC) is not licensed in this setting, although it is being used in Europe because it has a higher concentration of clotting factor levels, and it can be administered rapidly and in small volume, resulting in less volume overload during cardiac surgery. METHODS: PROPHESY is a pragmatic, single-centre, open-label, randomised, controlled pilot trial that will assess whether it is feasible to perform a large trial in the future that will compare PCC versus FFP in patients who are bleeding (not on warfarin) and who require blood transfusion. Over a 15-month period, 50 patients will be randomised to PCC versus FFP if they develop active bleeding within 24 h of cardiac surgery and for whom the clinician has decided to administer FFP for treatment of bleeding. Standard laboratory and point-of-care assessments will be performed as per routine practice, and additional research blood samples will be taken at three time points to assess haemostasis. Subjects will be assessed daily up to hospital discharge or 30 days or death (whichever occurs first) and will be seen in follow-up for 90 days after surgery to assess for thromboembolic complications and hospital re-admission since discharge. Quality-of-life assessment will be performed pre-surgery and at 90 days post-surgery. We will also perform qualitative research with clinical experts and patients to explore the understanding of and experience with the interventions, as well as adherence to study procedures and protocol. DISCUSSION: There have been no randomised controlled trials that have compared the safety and efficacy of FFP versus PCC in cardiac surgery patients who are bleeding. This pilot study will assess if individual components of a large trial are deliverable to assess the safety and efficacy of the two blood products in the future. TRIAL REGISTRATION: EudraCT, 2018-003041-41; ClinicalTrials.gov, NCT03715348. Registered on 29 July 2018.

Air pollution and activation of implantable cardioverter defibrillators in London.

BACKGROUND: Air pollution may increase the incidence of ventricular cardiac arrhythmias. We investigated this in patients with implantable cardioverter defibrillators attending London clinics. METHOD: We explored associations between dates of activation of defibrillators and daily concentrations of various metrics of particulate matter and of pollutant gases at lags from 0 to 5 days, using a fixed-stratum case-crossover analysis controlling for confounding factors. RESULTS: Over an average of 1200 days of observation, 705 patients experienced 5462 activation days. Of 11 pollutants considered, we found positive associations with particle sulfate, particulate matter with aerodynamic diameter less than 10 microm and less than 2.5 microm, ozone, and sulfur dioxide. Only the association for particle sulfate was not easily explainable by chance (for 1 microg/m, lag 0-1 day, odds ratio = 1.025 [95% confidence interval = 1.003 to 1.047]). There was little or no evidence of associations with markers of primary vehicle emissions (particle number concentration, black smoke, nitrogen oxides, and carbon monoxide). There was little evidence of interactions with clinical factors such as ischemic heart disease, frequency of activation, or cardiac drugs. CONCLUSION: Overall there was little evidence of an association between air pollution and activation of implantable cardioverter defibrillators. The pollutants with positive associations tended to be those of secondary origin with a regional distribution, rather than primary pollutants emitted from transport sources.