2 research outputs found
Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19.
BACKGROUND
Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results.
OBJECTIVES
We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19.
METHODS
Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group.
RESULTS
Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent.
CONCLUSIONS
Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079).Dr Stone has received speaker honoraria from Medtronic, Pulnovo,
Infraredx, Abiomed, and Abbott; has served as a consultant to
Daiichi-Sankyo, Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Ancora, Elucid Bio, Occlutech,
CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore,
Amgen, Adona Medical, and Millennia Biopharma; and has equity/
options from Ancora, Cagent, Applied Therapeutics, Biostar family of
funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix,
and Xenter; his daughter is an employee at IQVIA; and his employer,
Mount Sinai Hospital, receives research support from Abbott,
Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, BiosenseWebster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr
Farkouh has received institutional research grants from Amgen,
AstraZeneca, Novo Nordisk, and Novartis; has received consulting
fees from Otitopic; and has received honoraria from Novo Nordisk. Dr
Lala has received consulting fees from Merck and Bioventrix; has
received honoraria from Zoll Medical and Novartis; has served on an
advisory board for Sequana Medical; and is the Deputy Editor for the
Journal of Cardiac Failure. Dr Moreno has received honoraria from
Amgen, Cuquerela Medical, and Gafney; has received payment for
expert testimony from Koskoff, Koskoff & Dominus, Dallas W. Hartman, and Riscassi & Davis PC; and has stock options in Provisio. Dr
Goodman has received institutional research grants from Bristol
Myers Squibb/Pfizer Alliance, Bayer, and Boehringer Ingelheim; has
received consulting fees from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL
Behring, Ferring Pharmaceuticals, HLS Therapeutics, Novartis, Pendopharm/Pharmascience, Pfizer, Regeneron, and Sanofi; has received
honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim,
Bristol Myers Squibb, Eli Lilly, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, and Servier; has served on Data
Safety and Monitoring boards for Daiichi-Sankyo/American Regent
and Novo Nordisk A/C; has served on advisory boards for Amgen,
AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL
Behring, Eli Lilly, Ferring Pharmaceuticals, HLS Therapeutics, JAMP
Pharma, Merck, Novartis, Pendopharm/Pharmascience, Pfizer,
Regeneron, Sanofi, Servier, and Tolmar Pharmaceuticals; has a leadership role in the Novartis Council for Heart Health (unpaid); and
otherwise has received salary support or honoraria from the Heart
and Stroke Foundation of Ontario/University of Toronto (Polo) Chair,
Canadian Heart Failure Society, Canadian Heart Research Centre and
MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating
Centre for Clinical Research, Duke Clinical Research Institute, New
York University Clinical Coordinating Centre, PERFUSE Research
Institute, and the TIMI Study Group (Brigham Health). Dr Ricalde has
received consulting fees from Medtronic, Servier, and Boston Scientific; has received honoraria from Medtronic, Pfizer, Merck, Boston
Scientific, Biosensors, and Bayer; has served on an advisory board for
Medtronic; and has leadership roles in SOLACI and Kardiologen. Dr
Payro has received consulting fees from Bayer Mexico; has received
honoraria from Bayer, Merck, AstraZeneca, Medtronic, and Viatris;
has received payments for expert testimony from Bayer; has received
travel support from AstraZeneca; has served on an advisory board for
Bayer; and his institution has received equipment donated from
AstraZeneca. Dr Castellano has received consulting fees and honoraria from Ferrer International, Servier, and Daiichi-Sankyo; and has
received travel support from Ferrer International. Dr Hung has served
as an advisory board member for Pfizer, Merck, AstraZeneca, Fosun,
and Gilead. Dr Nadkarni has received consulting fees from Renalytix,
Variant Bio, Qiming Capital, Menarini Health, Daiichi-Sankyo, BioVie,
and Cambridge Health; has received honoraria from Daiichi-Sankyo
and Menarini Health; has patents for automatic disease diagnoses
using longitudinal medical record data, methods, and apparatus for
diagnosis of progressive kidney function decline using a machine
learning model, electronic phenotyping technique for diagnosing
chronic kidney disease, deep learning to identify biventricular
structure and function, fusion models for identification of pulmonary
embolism, and SparTeN: a novel spatio-temporal deep learning
model; has served on a Data Safety and Monitoring Board for CRIC
OSMB; has leadership roles for Renalytix scientific advisory board,
Pensive Health scientific advisory board, and ASN Augmented Intelligence and Digital Health Committee; has ownership interests in
Renalytix, Data2Wisdom LLC, Verici Dx, Nexus I Connect, and Pensieve Health; and his institution receives royalties from Renalytix. Dr
Goday has received the Frederick Banting and Charles Best Canada
Graduate Scholarship (Doctoral Research Award) from the Canadian
Institutes of Health Research. Dr Furtado has received institutional
research grants from AstraZeneca, CytoDin, Pfizer, Servier, Amgen,
Alliar Diagnostics, and the Brazilian Ministry of Health; has received
consulting fees from Biomm and Bayer; has received honoraria from
AstraZeneca, Bayer, Servier, and Pfizer; and has received travel support from Servier, AstraZeneca, and Bayer. Dr Granada has received
consulting fees, travel support, and stock from Cogent Technologies
Corp; and has received stock from Kutai. Dr Contreras has served as a
consultant for Merck, CVRx, Novodisk, and Boehringer Ingelheim;
and has received educational grants from Alnylam Pharmaceuticals
and AstraZeneca. Dr Bhatt has received research funding from Abbott,
Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen,
AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific,
Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi,
Cincor, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring
Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly,
Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo
Nordisk, Owkin, Pfizer Inc, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The
Medicines Company, Youngene, and 89bio; has received royalties
from Elsevier; has received consultant fees from Broadview Ventures
and McKinsey; has received honoraria from the American College of
Cardiology, Baim Institute for Clinical Research, Belvoir Publications,
Boston Scientific, Cleveland Clinic, Duke Clinical Research Institute,
Mayo Clinic, Mount Sinai School of Medicine, Novartis, Population
Health Research Institute, Rutgers University, Canadian Medical and
Surgical Knowledge Translation Research Group, Cowen and Company, HMP Global, Journal of the American College of Cardiology, K2P,
Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME,
Piper Sandler, Population Health Research Institute, Slack Publications, WebMD, Wiley, Society of Cardiovascular Patient Care; has
received fees from expert testimony from the Arnold and Porter law
firm; has received travel support from the American College of Cardiology, Society of Cardiovascular Patient Care, American Heart Association; has a patent for otagliflozin assigned to Brigham and
Women’s Hospital who assigned to Lexicon; has participated on a
data safety monitoring board or advisory board for Acesion Pharma,
Assistance Publique-Hôpitaux de Paris, AngioWave, Baim Institute,
Bayer, Boehringer Ingelheim, Boston Scientific, Cardax, CellProthera,
Cereno Scientific, Cleveland Clinic, Contego Medical, Duke Clinical
Research Institute, Elsevier Practice Update Cardiology, Janssen,
Level Ex, Mayo Clinic, Medscape Cardiology, Merck, Mount Sinai
School of Medicine, MyoKardia, NirvaMed, Novartis, Novo Nordisk,
PhaseBio, PLx Pharma, Regado Biosciences, Population Health
Research Institute, and Stasys; serves as a trustee or director for
American College of Cardiology, AngioWave, Boston VA Research
Institute, Bristol Myers Squibb, DRS.LINQ, High Enroll, Society of
Cardiovascular Patient Care, and TobeSoft; has ownership interests in
AngioWave, Bristol Myers Squibb, DRS.LINQ, and High Enroll; has
other interests in Clinical Cardiology, the NCDR-ACTION Registry
Steering Committee; has conducted unfunded research with FlowCo
and Takeda, Contego Medical, American Heart Association Quality
Oversight Committee, Inaugural Chair, VA CART Research and Publications Committee; and has been a site co-investigator for Abbott,
Biotronik, Boston Scientific, CSI, St Jude Medical (now Abbott),
Phillips SpectraWAVE, Svelte, and Vascular Solutions. Dr Fuster declares that he raised $7 million from patients for this study granted to
Mount Sinai Heart, unrelated to industry. All other authors have reported that they have no relationships relevant to the contents of this
paper to disclose.S
Efficacy and safety of fixed dose combination of Sitagliptin, metformin, and pioglitazone in type 2 Diabetes (IMPACT study): a randomized controlled trial
Abstract Background Due to the progressive decline in β-cell function, it is often necessary to utilize multiple agents with complementary mechanisms of action to address various facets and achieve glycemic control. Thus, this study aimed to evaluate the efficacy and safety of a fixed-dose combination (FDC) of metformin/sitagliptin/pioglitazone (MSP) therapy vs. metformin/sitagliptin (MS) in type 2 diabetes mellitus (T2DM). Methods In this phase 3, multicenter, double-blind study, patients with T2DM who exhibited inadequate glycemic control with HbA1c of 8.0–11.0% while taking ≥1500 mg/day metformin for at least 6 weeks were randomized to receive either FDC of MSP (1000/100/15 mg) or MS (1000/100 mg) per day for 24 weeks. The primary outcome measure was the change in HbA1c, and secondary outcomes included changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and body weight from baseline to 24 weeks along with safety and tolerability. Results Among the 236 patients randomized, 207 (87.71%) successfully completed the study. All baseline characteristics were comparable between the FDC of MSP and MS groups. There was a subsequent significant reduction of HbA1c in FDC of MSP (− 1.64) vs. MS (− 1.32); between groups was [− 0.32% (95% CI, − 0.59, − 0.05)], P = 0.0208. Similar reductions were found in FPG [− 13.2 mg/dL (95% CI, − 22.86, − 3.71)], P = 0.0068, and PPG [− 20.83 mg/dL (95% CI, − 34.11, − 7.55)], P = 0.0023. There were no significant changes in body weight. A total of 27 adverse effects (AEs) and one severe AE were reported, none of which were related to the study drug. Conclusion The FDC of MSP demonstrated significant efficacy in managing glycemic indices and could serve as a valuable tool for physicians in the management of Indian patients with T2DM. Trial registration Clinical Trials Registry of India, CTRI/2021/10/037461