Table 9.

Characteristics of ongoing studies [ordered by study ID]

AdDIT
Trial name or title	Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT)
Methods	Study design: Multicenter RCT; 2×2 factorial design; randomization with minimization with primary intent-to-treat analysis and secondary ‘as treated’ analysis Unit of randomization and analysis: individual Number randomized - Total: not reported Per group: not reported Sample size calculation: Yes; “This sample size is informed by the ORPS cohort study (477 participants in the correct age range of recruitment with a mean of 3.5 observations over time)”
Participants	Country: United Kingdom, Australia, and Canada Study period: not reported Age: not reported Gender: not reported Race/ethnicity: not reported Inclusion criteria: type 1 diabetics 11 to 16 years of age with albumin/creatinine ratio measured twice from average of 3 early-morning samples; adjusted for gender, age, and duration of diabetes; eligible whenever “subject’s residual lies above log 1.2” (i.e. higher side); < 1 year since diagnosis or C-peptide negative Exclusion criteria: “the presence of any of the following will prevent patient inclusion: 1) Non T1D, i.e. type 2 diabetes, insulin dependent diabetes related to monogenic disease, secondary diabetes; 2) ACR based on six early morning urines deemed to be at low risk for subsequent development of CVD or DN; 3) Pregnancy or unwillingness to comply with contraceptive advice and regular testing throughout trial; 4) Breast feeding; 5) Severe hyperlipidaemia and family history data to support diagnosis of familial hypercholesterolaemia; 6) Established hypertension unrelated to DN; 7) Prior exposure to the investigational products; 8) Unwillingness/inability to comply with the study protocol; 9) Other co-morbidities considered unsuitable by the investigator (excluding treated hypothyroidism and celiac disease); 10) Proliferative retinopathy.” Type of diabetes: type 1 HbA1c categories/levels: not reported Retinopathy status: not reported
Interventions	Intervention 1: ACE inhibitor Intervention 2: statin Intervention 3: combination of ACE inhibitor and statin Intervention 4: placebo Length of follow-up: Planned: 5 to 10 years Actual: not reported
Outcomes	Primary study outcome: reduction in albumin/creatinine ratio (30% assumed; 25% advantage) using the area under the curve of the log albumin/creatinine ratio standardized for gender, age, and duration of diabetes Secondary study outcomes: changes in 1) carotid intima-media thickness, fibromuscular dysplasia, endothelial dysfunction, and pulse wave velocity; 2) arterial blood pressure, lipids, and other lipoproteins, cardiovascular disease risk markers (high-sensitivity C-reactive protein and asymmetric dimethylarginine); 3) measure of glomerular filtration rate (plasma symmetric dimethyl arginine, creatinine, and cystatin C); 4) retinopathy scores and retinal microvascular structure; 5) quality of life and health economics Intervals at which outcomes were assessed: every 3 months Eyes examined for outcome: not reported Cost of interventions: not reported Quality of life: not reported
Starting date	Registered in 2007 and publication expected in 2009
Contact information	The Adolescent type 1 Diabetes cardio-renal Intervention Trial Research Group (dbd25@cam.ac.uk)
Notes	Source of funding: Juvenile Diabetes Research Foundation, British Heart Foundation, and Diabetes UK. Study drugs are supplied by Pfizer UK Ltd. The study is also funded in Canada by the Canadian Diabetes Association and the Heart and Stroke Foundation of Canada Declaration of interest: “The author declares that they have no competing interests” Target sample size: 500 For retinopathy, expect > 90% power to detect 25% difference in “retinopathy prevalence” using retinal photographs EudraCT number: 2007-001039-72 Trial Registration Number: ISRCTN91419926
NCT00134160
Trial name or title	The Study Comparing the Incidence of Cardiovascular Events Between High-Dose ARB Monotherapy and Combination Therapy With ARB and Calcium Channel Blocker in Japanese Elderly Hypertensive Patients at High Cardiovascular Risk
Methods	Study design: Parallel group RCT Unit of randomization and analysis: individual Number randomized - Total: not reported Per group: not reported Sample size calculation: not reported
Participants	Country: Japan Study period: not reported Age: not reported Gender: not reported Race/ethnicity: not reported Inclusion criteria: individuals aged 65 to 85 years on anti-hypertensive therapy (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg) with either type 2 diabetes, cardiovascular risk factors, elevated serum creatinine, or proteinuria Exclusion criteria: “Secondary hypertension or malignant hypertension; Heart failure (NYHA functional classification III or IV); Required treatment for malignant tumor; Serious liver or renal dysfunction (serum creatinine > 2.5 mg/dL or with dialysis treatment); Not appropriate for change to the test drugs from current therapy for hypertension or coronary diseases (i.e. calcium channel blockers, β-blockers, thiazide diuretics, etc.); History of serious adverse drug reactions to angiotensin II receptor blockers or calcium channel blockers; Patients with other serious reasons (i.e. illness, significant abnormalities, etc.) that investigators judge inappropriate for the study” Type of diabetes: type 2 HbA1c categories/levels: not reported Retinopathy status: not reported
Interventions	Intervention 1: ARB therapy: olmesartan medoxomil 40 mg/day Intervention 2: Combination therapy: ARB and calcium channel blocker (olmesartan medoxomil 20 mg/day and either amlodipine or azelnidipine) Length of follow-up: Planned: 36 months Actual: not reported
Outcomes	Primary study outcome: composite fatal and nonfatal cardiovascular events; coronary events; heart failure; vascular events; diabetic complications (nephropathy, retinopathy, neuropathy); renal dysfunction; all-cause mortality Secondary study outcomes: change in blood pressure; serious adverse events not including primary outcomes Intervals at which outcomes were assessed: not reported Eyes examined for outcome: not reported Cost of interventions: not reported Quality of life: not reported
Starting date	August 2005
Contact information	Kikuo Arakawa, MD Emeritus Professor, Fukuoka University Fukuoka, Japan
Notes	ClinicalTrials.gov identifier: NCT00134160
NCT00300976
Trial name or title	Japan Diabetes Optimal Integrated Treatment Study for 3 Major Risk Factors of Cardiovascular Diseases (J-DOIT3)
Methods	Study design: Parallel group RCT Unit of randomization and analysis: individual Number randomized - Total: not reported Per group: not reported Sample size calculation: not reported
Participants	Country: Japan Study period: not reported Age: not reported Gender: not reported Race/ethnicity: not reported Inclusion criteria: Individuals aged 45 to 70 years with type 2 diabetes with 1 of the following: 1) HbA1c ≥ 6.9% despite therapy and lifestyle interventions; 2) SBP ≥ 140 mmHg or DBP ≥ 90 mmHg when not on anti-hypertensive therapy or SBP of 130 mmHg or DBP of 80 mmHg on ACE inhibitors, ARBs, and/or long-acting calcium channel blockers; 3) abnormalities in lipid metabolism Exclusion criteria: “1. Those with poorly controlled hypertension despite pharmacological therapy (systolic BP 200 mmHg or diastolic BP 120 mmHg) 2. Those on insulin therapy 3. Those with non-diabetic renal disease 4. Those in whom type 1 and other diabetes due to pathogenic mechanisms other than those associated with type 2 diabetes is strongly suspected 5. Those who tested anti-GAD antibody*-positive 6. Those with LDL-cholesterol 200 mg/dL 7. Those suspected of having secondary hypertension other than renal parenchymal hypertension 8. Those suspected of having hereditary lipid disorder with a strong family history of lipid metabolic disorder 9. Those who were receiving antihypertensive agents other than ARB, ACEI, long-acting CCB, except where they were receiving these agents for other purposes than blood pressure lowering 10. Those who were receiving 3 or more antihypertensive agents (i.e., ARB, ACEI, and long-acting CCB), except where they were receiving these agents for other purposes than blood pressure lowering 11. Those with more serious retinopathy than proliferative retinopathy 12. Renal failure (serum Cr: 2.0 mg/dL in men; 1.5 mg/dL in women) 13. Those with a history of cardiac failure or those with cardiac failure 14. Those who were pregnant or potentially pregnant 15. Those who met any of the following criteria and who had BNP 100 pg/mL, Myocardial infarction, Angina pectoris (or a history of disease), History of coronary artery bypass graft (CABG), History of percutaneous coronary angioplasty (PTCA), Other cardiac disease, ECG findings of left ventricular hyperplasia, Abnormal ECG findings (excluding isolated extrasystole or right bundle branch block (RBBB)) 16. Those judged by the physician in charge to be ineligible for study entry” Type of diabetes: type 2 HbA1c categories/levels: not reported Retinopathy status: not reported
Interventions	Intervention 1: Intensive therapy: weight control, diet, and exercise through lifestyle consultation; and drug therapy to achieve HbA1c < 6.2%, SBP/DBP < 120/75 mmHg, high-density lipoprotein cholesterol of 40 mg/dL, low-density lipoprotein cholesterol < 80 mg/dL, triglycerides < 120 mg/dL Intervention 2: Conventional therapy: weight control, diet, and exercise according to standard guidelines Length of follow-up: Planned: not reported; follow up every 6 or 12 months Actual: not reported
Outcomes	Primary study outcome: incidence of cardiovascular events Secondary study outcomes: incidence or progression of nephropathy, retinopathy, incidence of peripheral vascular events Intervals at which outcomes were assessed: every 6 or 12 months Eyes examined for outcome: not reported Cost of interventions: not reported Quality of life: not reported
Starting date	May 2006
Contact information	Takashi Kadowaki University of Tokyo
Notes	ClinicalTrials.gov identifier: NCT00300976

ACE: angiotensin-converting enzyme ARBs: angiotensin II receptor blockers DBP: diastolic blood pressure HbA1c: glycated hemoglobin mg/dL: milligram per deciliter mmHg: millimeter of mercury ORPS: Oxford Regional Prospective Study RCT: randomized controlled trial SBP: systolic blood pressure