BACKGROUND – THE STUDY QUESTION
Background • In type 2 diabetes, the body’s cells is resistance to insulin which results in excess blood sugar.
• Canagliflozin inhibits sodium-glucose cotransporter-2.
• the kidney-based inhibition reduces the rate at which glucose is reabsorbed. The latter results in increased glucose excretion via urine and reduced plasma glucose.
• The drug is indicated for diabetes and can be administered for hypertension, obesity and albuminuria.•
Previous trials • CANVAS- Began in November 2009 and ended March 2014. This trial occurred before the approval of canagliflozin by the FDA. The initial purpose was to determine cardiovascular safety, and assess adverse effects associated with the Canagliflozin
• CANVAS-R- Began in January 2014 and ended May 2015. This trial is post market research to measure cardiovascular safety and measure effects on albuminuria
Why this study? • Establishing canagliflozin’s effects on the cardiovascular and renal systems, alongside general safety concerns when patients are put von the drug.
GENERAL STUDY OVERVIEW
SUMMARY CRITIQUE
Funding • Janssen Research and Development: CANVAS
• CANVAS-R Clinical Trials.gov • Two interested bodies funding the research to inform their practice
Trial design • Double-blind, placebo-controlled
• Trial and randomized trial designs • Randomized trials enabled accuracy and bias during the study
Null Hypothesis • Death resulted from any causes like progression of albuminuria, cardiovascular complications and/or heart failure.
• Death could not be directly caused and/or influenced by the factors mentioned. The latter were not the basis of the research.
Objectives • Establishing the outcomes of canagliflozin on cardiovascular complications among type 2 diabetes patients. • The outcomes of the drug inform its indications and contraindications for diabetic patients.
Enrollment • Patients aged averagely 63.3 years. 64.2% males and 35.8% females.
• 65.6% of the specimen suffered from the disease and the mean duration for diabetes was 13.5 years.
• The nature of the enrollment enables collection of the most actionable and relevant data on the drug and its implications on patients.
METHODS
SUMMARY CRITIQUE
Inclusion criteria • Raw data to illustrate and test the theme – males and females suffering from the disorder were randomly selected and subjected to the study
• Patients with a history of cardiovascular illnesses are primary targets
• Childbearing women, or simply fertile women, must test negative for the hormone, beta-HCG, during screening. • The participants provided raw data following administration of the drug
Exclusion criteria • Qualitative methodology: hazard ratio of 1:3 • The hazard ratio was integral to the registration of the adverse effects of the drug among the participants.
Randomization • Centrally-executed randomization via a Web-based response system.
• They are also accompanied by permuted blocks.
• Computer-generated schedules were used. • Computer-generated randomization enhances accuracy and potentiate the validity of the outcomes
Interventions • Monitoring patients
• Follow-up programs on patients to which the drug is administered.
• CANVAS participants were assigned in the ration of 1:1:1.
• They received a placebo, 100 mg and 300 mg canagliflozin
• CANVAS-R were assigned the ration 1:1
• They received a placebo and a canagliflozin.
• Canagliflozin was initially administered daily, 100 mg and after the 13th week, 300 mg.
• Dose consumption: daily dose intake following a 2-weeksingle-blind run-in period where placebo was consumed,
• • Follow-ups enhanced the accuracy and validity of the study
• Controlling and monitoring the progress of the groups is key to the development of the concept.
Primary Endpoints • Non-fatal, MI or stroke and CV mortality • • • Patients are likely to die of cardiovascular complications mentioned earlier
•
Secondary Endpoints • All causes of mortality • Some cardiovascular and systemic complications may not result in patient death even though they are related to the condition
Statistical analyses • Statistics indicate the effectiveness of the drug on diabetic patients. The landscape of the statistical revelation is quite dynamic and extensive, as displayed in the article • the implications of the drug is displayed in the article. They display a multidimensional effects and implications of the drug and its effectiveness among the target group
RESULTS
SUMMARY CRITIQUE
Enrollment • Patients with extensive periods of the disease potentially provide the most relevant results on the same. • Participants must be carefully enrolled and recruited in the study process to obtain best results.
Monitoring • Frequent participant follow-up and evaluation • Participant evaluation and follow-up is necessary for analyzing the progress of their conditions.
Baseline characteristics • Type 2 diabetes patients likely to face cardiovascular complications, amputation and possibly death.
• Amputation and cardiovascular complications are probable among type 2 diabetes patients. The cardiovascular complications can result in death.
Primary Outcome Composite death resulting from cardiovascular complications, nonfatal stroke and/or nonfatal myocardial infarction.
• Nonfatal stroke and myocardial infarction are possible triggers of death among type 2 diabetes patients
Secondary Outcomes • Death resulted from cardiovascular causes, hospitalization courtesy of heart failure and/or progression of albuminuria. • Cardiovascular complications like heart failures and/or albuminuria’s progression do not independently trigger death
Adverse Events • Pharmacological adverse reactions
• Amputation
• Nonresponsive participants during follow-up • The drug increased chances of amputation
AUTHORS’ CONCLUSIONS
Type 2 diabetes patients treated with canagliflozin displayed lower cardiovascular stress and complications than those who did not, and the converse is true
GENERALIZABILITY/CRITIQUE/DISCUSSION
Strengths
• The article/study benefited from a large sample size, combined trials, length trial durations, high standards of trials and a wide breadth of participants.
• Possible renal protection
• Patients who received canagliflozin displayed low hospitalization rates than those who received a placebo
Limitations
• Moderate events around essential outcomes, especially paucity of events concerning end-stage kidney disease.
• Large number of studies and analysis that increase the probability of false results.
• Advantageous to weight and hypertension
• Decreased cardiovascular hospitalization
Discussion
• Canagliflozin is an effective drug for reducing cardiovascular-related mortality among type 2 diabetes
• Increasing amputation cases among type 2 diabetes patients
• Terminating randomized therapy, alongside administration glucose-reducing medications, among members of the placebo group, during the trial, is a potential account for the convergence and increase in hemoglobin levels.
• The latter may have resulted underestimation of other advantages and disadvantages of canagliflozin.
EVALUATOR CONCLUSIONS
Canagliflozin is a remarkable drug for diabetes-related cardiovascular complications. It prevents amputation and reduces mortality rates.
References
Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12. PMID: 28605608
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