Understanding the trajectory of functional recovery of older hospitalised patients with COVID in the short- and long-term is critical to improving patient outcomes and informing health and rehabilitative interventions for survivors.
The addition of a prospective cohort study extension to COREG will allow the investigators to follow-older hospitalised COVID patients over the longer-term in order to gain an understanding of the trajectory of functional recovery of the disease. Combining the primary data collection with COREG will also allow the investigators to identify determinants of long-term outcomes for at-risk older adults.
These data are necessary to guide the clinical care and optimal management of older patients who survive serious COVID illness. Retrospective Cohort The retrospective cohort will assess patients at 3, 6, 9, and months after being discharged from the hospital.
Change in Clinical Frailty Scale CFS for participants over 60 years of age [ Time Frame: Admission to hospital ward days post ward admission, to capture pre-morbid function , and at 3,6,9 and months post hospital discharge ] The CFS is an interview-based scale wherein the assessor may ask the participant questions about things such as a participant's independence or physical abilities to determine where the participant falls along the 9-point scale, from 1 Very Fit to 9 Terminally Ill.
Change in Forced Expiratory Volume FEV1 [ Time Frame: 3,6,9 and months post hospital discharge ] The Forced Expiratory Volume in 1 Second parameter measures the volume of air that was exhaled into the mouthpiece in the first second after a full inhalation as measured by spirometry.
Change in Forced Vital Capacity FVC [ Time Frame: 3,6,9 and months post hospital discharge ] The amount of air that can be forcibly exhaled from a participant's lungs after taking the deepest breath possible, as measured by spirometry.
Each item is rated on a 5-point scale, from 0 "not at all" to 4 "extremely". Lower grades indicate better functioning, with grade 0 representing the absence of symptoms or functional limitations and grade 4 reflecting severe limitations and symptom burden. The PCFSS can be patient-reported following a flow diagram series of questions to result in a grade, or it can be administered via structured interview, which is more comprehensive.
The research team will conduct the structured interview over the phone and the patient-reported flow chart during the home visits.
Scores range from 0 to 21, with higher scores indicating higher levels of anxiety. Change in Fatigue Visual Analog Scale Fatigue VAS [ Time Frame: 3,6,9 and months post hospital discharge ] This visual scale allows individuals to rate a participant's global fatigue from 0 worst fatigue to 10 normal.
Change in Modified Medical Research Council MRC Breathlessness Scale [ Time Frame: 3,6,9 and months post hospital discharge ] This brief questionnaire contains five statements describing a range of breathlessness from only becoming breathless with strenuous exercise to being too breathless to leave the house. Change in Oxygen Saturation SpO2 [ Time Frame: 3,6,9 and months post hospital discharge ] Oxygen saturation will be measured using a fingertip pulse oximeter to detect hypoxia and to evaluate any persistent hypoxia post-COVID illness.
Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below.
For general information, Learn About Clinical Studies. Criteria Inclusion Criteria:. Try the modernized ClinicalTrials. No differences were seen between the two groups as it comes to worsening in heart failure, hospitalizations, and cause-specific hospitalizations Torp-Pedersen, Poole-Wilson, et al Mean duration of follow-up was 58 months, but the benefit, in concern of reduced mortality among the patients treated with carvedilol, appeared already at 6 months of observation.
Lancet, — Criticism has been focused on the choice of formulation of metoprolol. The question is then whether this formulation can improve mortality and is worthy of comparison with carvedilol. Need for transplantation was used as an expression for deterioration of heart failure. No reduction in all-cause mortality was observed, possibly due to a very low number of deaths in the trial. But when follow up was extended a beneficial effect on mortality was indeed observed with IR metroprolol MDC The basic question is, whether the apparent superior effect on mortality seen with carvedilol compared with IR metoprolol, has any relevance to a higher dose and more sustained blockade that is obtained with mg of CR metoprolol as was used in MERIT-HF.
To assess the degree of beta1-blockade the most accepted method is to study exercise-induced increase in heart rate HR. In the COMET trial no evaluation of the relative beta1-blockade of the two beta-blockers used was performed.
The only information collected was the resting HR. A significant albeit small difference in the reduction of HR obtained was observed in the carvedilol arm, no difference in HR was seen beyond the f irst year of observation Figure 2 Packer As carvedilol exert different adrenoceptor blocking properties besides its antioxidative effect, it is of interest to know which mechanism gives carvedilol its favorable effect in superiority to metoprolol on mortality.
The alpha-blocking properties have been tested. Doxazosin, a selective alpha1-blocker, versus placebo was tested in 73 patients with CHF DiBianco et al Both investigators and patients assessment of symptomatic change was improved after treatment with doxazosin. When doxazosin was added to the beta1-blocker metoprolol in patients with heart failure, no improvement in hemodynamic measurements were seen, when compared with patients only treated with metoprolol Kukin et al Even though carvedilol does not have the same pharmacokinetic properties as the combination of doxazosin and metoprolol, this study indicates that the beneficial effect seen with carvedilol is less likely to be caused solely by the alpha1-blocking properties of carvedilol.
The beta2-blocking effect affects the pre-synaptic release of NE, which reduces the amount of NE that can stimulate the beta1-receptors. Sub-studies from the COMET trial showed a decreased number of new-onset diabetes in the carvedilol arm, this sub-study is published as an abstract Torp-Pedersen, Cleland, et al This was in contrast to earlier findings from beta-blocker trials showing an increased number of new-onset diabetes when treated with traditional beta1-receptor blockers Dahlof et al That carvedilol might have a beneficial effects on the glucose metabolism was already shown in a study by Jacob and colleagues In this study metoprolol was compared with carvedilol in a group of patients with hypertension.
An improvement in insulin sensitivity was seen among those treated with carvedilol. Guigliano also showed improved insulin sensitivity when treated with carvedilol. The changes were shown by making an insulin clamp testing. Recently a large randomized trial in which the two beta-blockers were compared concerning their abilities in affecting the metabolic control in patients with diabetes and hypertension was published Bakris et al An increase in glycosylated hemoglobin was seen in the metoprolol arm, whereas no change was seen in the carvedilol arm.
Improvement in insulin sensitivity was seen in the carvedilol group and no change was seen among the patients treated with metoprolol. In both trials the IR metoprolol was used. The beneficial role of carvedilol is speculated to be caused by its alpha-blocking properties and thereby causing vasodilation. Peripheral vasodilation facilitates glucose uptake in skeletal muscle and thereby improves insulin sensitivity Smith and Warren Other anti-hypertensives that also increase peripheral blood-flow have the same benef icial effect on insulin sensitivity Lind and Lithell Whether the increased peripheral blood-flow is solely to explain the benefit of carvedilol on insulin sensitivity is doubtful.
The combined effect of carvedilol, including its antioxidative properties, is more likely to be the explanation. The perspective of COMET can be divided in 3 parts: the importance of beta-1 inhibition, the importance of other effects of carvedilol and the clinical consequence.
Three beta-blockers with beta-1 activity have been shown to reduce mortality in CHF. One interpretation of COMET is that a more effective inhibition by carvedilol, either because of a higher dose being given or because carvedilol has a higher affinity for the beta-1 receptor, explained the marked difference. Thus effective beta-1 inhibition with as high a dose as possible is clearly important for the treatment of CHF.
Therefore, it is likely that other effects of carvedilol compared with metoprolol are important for the treatment of heart failure. Further research is necessary to clarify whether beta-2 inhibition, alpha-1 inhibition, antioxidative properties of, inhibition of endothelin-1biosynthesis, or yet another effect is beneficial Table 1.
The possible effect of the adrenoreceptors in the progression of heart failure. Beta-blockers in heart failure: are pharmacological differences clinically important? Heart Fail Rev, — As for the clinical consequence at this time what remains is a continuing debate. National Center for Biotechnology Information , U. Vasc Health Risk Manag. Carvedilol controlled release 10, 20, 40 or 80 mg and placebo taken in the morning. Outcome Measures. Eligibility Criteria. Information from the National Library of Medicine Choosing to participate in a study is an important personal decision.
NOTE: Female subjects must be post-menopausal i. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Please refer to this study by its ClinicalTrials. More Information. Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure.
The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. Carvedilol Heart Failure Study Group. N Engl J Med. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. Safety and efficacy of carvedilol in severe heart failure. The U. J Card Fail. Carvedilol improves left ventricular function and symptoms in chronic heart failure: a double-blind randomized study. J Am Coll Cardiol. Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease.
Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Dargie HJ. Epub Jan 5. The proponents of carvedilol assembled a collection of compelling arguments both during and after the disputatious FDA debate.
There was no question about the strength of the US Carvedilol's programs findings. Lives were prolonged for patients who had a disease that had no known definitive therapy and whose prevalence was rapidly rising. The FDA was reminded that the most compelling of all endpoints in clinical trials is total mortality, and the most laudable goal was prolonging life. There was no doubt that carvedilol had produced this precise result in the US Carvedilol Program.
In addition, the research community was asked to recall that at the outset of a research effort, investigators cannot be expected to identify the totality of the analyses that they will want to carry out at the study's conclusion.
While scientists will certainly want to have a prospectively asked question that motivate the generation of the sample, the logistical efficiency of the research effort requires that they collect data extending above and beyond the prospectively declared analyses. When the manuscripts are submitted for publication, the authors must affirmatively reply to persistent journal reviewers and editors who may like to see additional analyses carried out so that the reader will have all relevant information required to make an independent judgment about the intervention's risk-benefit balance.
To do anything else would open the investigators to the criticism of concealing critical information. Finally, the sponsors were obligated to collect safety data.
It was the FDA, the Advisory Committee was told, that required the US Carvedilol Program to collect mortality data in order to provide assurances that carvedilol did not shorten lives.
Was the FDA, they asked, now to ignore the data they themselves demanded when the data demonstrated an unsuspected benefit of the drug? The US Carvedilol Program had complied with the requirements of the FDA in the design of the program and the studies' interim monitoring.
From its advocates' point of view, scientists who criticized the US Carvedilol Program for not finding a statistically significant reduction in weaker endpoints e. The Data Safety and Monitoring Committee is a collection of distinquished scientists responsible for evaluating the interim results of the study to ensure the ethical treatment of its participants. Unblinded to therapy assignment, and privy to all of the data, this committee can recommend that the study be prematurely terminated if unanticipated harm or benefit has occurred.
The asymmetry of safety findings is discussed in Chapter Eight.
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