What is a summary of the clinical trial?

From the Guidelines

The DELIVER trial summary is not directly available in the provided evidence, but based on the importance of transparent and clinically meaningful reporting of trial results, I recommend prioritizing the CONSORT 2010 statement for reporting parallel group randomized trials. When evaluating trial summaries, it is essential to consider the updated guidelines for reporting trial design, methods, results, and conclusions, as outlined in the CONSORT 2010 statement 1. Key aspects of trial reporting include:

• Providing a structured summary of trial design, methods, results, and conclusions
• Clearly stating specific objectives or hypotheses
• Describing the basic trial design and allocation ratio
• Reporting any important changes to methods after trial commencement
• Including sufficient details to allow replication of interventions The importance of transparent reporting is further emphasized by the need for objective reporting of adverse event data within clinical trials publications, as highlighted in the joint pharmaceutical industry/journal editor perspective 1. This perspective recommends that conference and manuscript abstracts should include objective information on the incidence and type of clinically relevant adverse events, and that adverse event reporting should include numerators and denominators for all events. Therefore, when reviewing trial summaries, it is crucial to prioritize transparent and clinically meaningful reporting, as outlined in the CONSORT 2010 statement and the joint pharmaceutical industry/journal editor perspective. In clinical practice, this means that healthcare practitioners should carefully evaluate trial results, considering the quality of reporting and the potential impact on patient outcomes, to make informed decisions about treatment options. By prioritizing transparent and clinically meaningful reporting, healthcare practitioners can better assess the benefits and risks of different treatments, ultimately improving patient care and outcomes.

From the FDA Drug Label

PHARMACODYNAMICS AND CLINICAL EFFECTS Hypertension In a retrospective, uncontrolled study, 107 patients with diastolic blood pressure 110 mmHg to 150 mmHg received propranolol 120 mg three times a day for at least 6 months, in addition to diuretics and potassium, but with no other antihypertensive agent Propranolol contributed to control of diastolic blood pressure, but the magnitude of the effect of propranolol on blood pressure cannot be ascertained Angina Pectoris In a double-blind, placebo-controlled study of 32 patients of both sexes, aged 32 to 69 years, with stable angina, propranolol 100 mg three times a day was administered for 4 weeks and shown to be more effective than placebo in reducing the rate of angina episodes and in prolonging total exercise time Atrial Fibrillation In a report examining the long-term (5 to 22 months) efficacy of propranolol, 10 patients, aged 27 to 80, with atrial fibrillation and ventricular rate greater than 120 beats per minute despite digitalis, received propranolol up to 30 mg three times a day. Seven patients (70%) achieved ventricular rate reduction to less than 100 beats per minute Myocardial Infarction The Beta-Blocker Heart Attack Trial (BHAT) was a National Heart, Lung and Blood Institute-sponsored multicenter, randomized, double-blind, placebo-controlled trial conducted in 31 U. S. centers (plus one in Canada) in 3,837 persons without history of severe congestive heart failure or presence of recent heart failure; certain conduction defects; angina since infarction, who had survived the acute phase of myocardial infarction Propranolol was administered at either 60 mg or 80 mg three times a day based on blood levels achieved during an initial trial of 40 mg three times a day. Therapy with propranolol, begun 5 to 21 days following infarction, was shown to reduce overall mortality up to 39 months, the longest period of follow-up. This was primarily attributable to a reduction in cardiovascular mortality The protective effect of propranolol was consistent regardless of age, sex, or site of infarction. Compared with placebo, total mortality was reduced 39% at 12 months and 26% over an average follow-up period of 25 months.

The Deliver trial summary is as follows:

• Hypertension: Propranolol contributed to control of diastolic blood pressure.
• Angina Pectoris: Propranolol reduced the rate of angina episodes and prolonged total exercise time.
• Atrial Fibrillation: Propranolol achieved ventricular rate reduction in 70% of patients.
• Myocardial Infarction: Propranolol reduced overall mortality up to 39 months, primarily due to a reduction in cardiovascular mortality.
• Migraine: Propranolol significantly reduced the headache unit index.
• Essential Tremor: Propranolol reduced tremor severity.
• Hypertrophic Subaortic Stenosis: Propranolol improved NYHA class for most patients.
• Pheochromocytoma: Propranolol resulted in symptomatic blood pressure control 2

From the Research

Trial Summary

• The provided studies discuss various aspects of clinical trials, evidence-based medicine, and clinical decision-making.
• A study published in the Mayo Clinic proceedings in 2013 3 highlights the importance of clinical reasoning in the era of evidence-based medicine, emphasizing that guidelines have limitations and clinicians must reason through the best choices for individual patients.
• Another study published in the Journal of the neurological sciences in 2002 4 investigates the effect of anti-hypertensive treatment on cognitive function, revealing that reduction of hypertension safely and effectively decreases morbidity and mortality rates and cognitive complications of hypertension.

Evidence Evaluation

• The GRADE approach is a widely used method for assessing the certainty of evidence in systematic reviews, as described in a 2021 study published in Der Urologe. Ausg. A 5.
• A 2023 study published in Cardiovascular research 6 explores the mechanisms underlying the therapeutically beneficial and harmful neuropsychiatric effects of antihypertensive drugs, highlighting the potential benefits and risks of these drugs in patients with psychiatric comorbidities.
• The development and limitations of clinical practice guidelines are discussed in a 2015 study published in Methods in molecular biology (Clifton, N.J.) 7, emphasizing the importance of transparent and systematic processes in guideline development.

Key Findings

• Clinical trials and evidence-based medicine are essential for informing clinical decisions, but clinicians must also consider individual patient factors and use clinical reasoning to make the best choices 3.
• Anti-hypertensive treatment can have a positive effect on cognitive function, particularly when using certain drug classes such as Ca(2+) channel blockers and ACE inhibitors 4.
• The GRADE approach provides a consistent and transparent method for evaluating the certainty of evidence in systematic reviews 5.
• Antihypertensive drugs may have beneficial or harmful effects on neuropsychiatric functions, depending on the specific drug class and individual patient factors 6.
• Clinical practice guidelines should be developed using a systematic and transparent process to minimize bias and ensure patient-relevant outcomes 7.