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POPADAD (antioxydant) study, 2008	TRC8776
[ISRCTN53295293]	download pdf: combination | antioxydants for cardiovascular prevention

Treatments

Studied treatment	antioxidant capsule containing (alpha-tocopherol 200 mg, ascorbic acid 100 mg, pyridoxine hydrochloride 25 mg, zinc sulphate 10 mg, nicotinamide 10 mg, lecithin 9.4 mg, and sodium selenite 0.8 mg)
Control treatment	placebo
Remarks	factorial design of aspirin plus antioxidant compared with aspirin alone, antioxidant alone, and placebo.

Patients

Patients	patients with diabetes mellitus and asymptomatic peripheral arterial disease
Inclusion criteria	adults of either sex, aged 40 or more, with type 1 or type 2 diabetes who were determined as having asymptomatic peripheral arterial disease as detected by a lower than normal ankle brachial pressure index (<=0.99)
Exclusion criteria	evidence of symptomatic cardiovascular disease; aspirin or antioxidant therapy on a regular basis; peptic ulceration, severe dyspepsia, a bleeding disorder, or intolerance to aspirin; suspected serious physical illness (such as cancer), which might have been expected to curtail life expectancy; psychiatric illness; congenital heart disease; unable to give informed consent
Baseline characteristics	Sexe M 43%  Age moyen 60 y

Method and design

Randomized effectives	640 / 636 (studied vs. control)
Design	Factorial plan
Blinding	double blind
Number of centre	multicentre
Geographic area	Scotland
Hypothesis	Superiority
Primary endpoint	CV events
Remarks	two hierarchical composite primary end points of death from coronary heart disease or stroke, non-fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke

Results

Endpoints and data reported in the trial's publication(s)

Endpoint	Events (%)		Relative Risk	95% CI
	Studied treat.	Control treat.
CHD death, stroke, MI, above ankle amputation	117 / 640 (18,3%)	116 / 636 (18,2%)	1,00	[0,79;1,26]
Death from coronary heart disease or stroke	42 / 640 (6,6%)	36 / 636 (5,7%)	1,16	[0,75;1,78]
Death (any cause)	115 / 640 (18,0%)	80 / 636 (12,6%)	1,43	[1,10;1,86]
Coronary heart disease death	30 / 640 (4,7%)	31 / 636 (4,9%)	0,96	[0,59;1,57]
Stroke death	12 / 640 (1,9%)	5 / 636 (0,8%)	2,39	[0,85;6,73]
Non-fatal myocardial infarction	49 / 640 (7,7%)	62 / 636 (9,7%)	0,79	[0,55;1,12]
Non-fatal stroke	36 / 640 (5,6%)	34 / 636 (5,3%)	1,05	[0,67;1,66]
Above ankle amputation for critical limb ischaemia	10 / 640 (1,6%)	10 / 636 (1,6%)	0,99	[0,42;2,37]
Transient ischaemic attack	11 / 640 (1,7%)	23 / 636 (3,6%)	0,48	[0,23;0,97]
Coronary artery bypass surgery	12 / 640 (1,9%)	14 / 636 (2,2%)	0,85	[0,40;1,83]
Coronary artery angioplasty	7 / 640 (1,1%)	8 / 636 (1,3%)	0,87	[0,32;2,38]
Development of angina	69 / 640 (10,8%)	79 / 636 (12,4%)	0,87	[0,64;1,18]
Peripheral arterial bypass surgery	4 / 640 (0,6%)	8 / 636 (1,3%)	0,50	[0,15;1,64]
Peripheral arterial angioplasty	12 / 640 (1,9%)	12 / 636 (1,9%)	0,99	[0,45;2,20]
Development of critical limb ischaemia	22 / 640 (3,4%)	18 / 636 (2,8%)	1,21	[0,66;2,24]
Development of claudication	97 / 640 (15,2%)	107 / 636 (16,8%)	0,90	[0,70;1,16]
Malignancy	65 / 640 (10,2%)	56 / 636 (8,8%)	1,15	[0,82;1,62]
Gastrointestinal bleeding	28 / 640 (4,4%)	31 / 636 (4,9%)	0,90	[0,54;1,48]
Gastrointestinal symptoms, including dyspepsia	69 / 640 (10,8%)	98 / 636 (15,4%)	0,70	[0,52;0,93]
Arrhythmia	50 / 640 (7,8%)	52 / 636 (8,2%)	0,96	[0,66;1,39]
Allergy including skin rash	68 / 640 (10,6%)	68 / 636 (10,7%)	0,99	[0,72;1,37]

Endpoints used by the meta-analysis and data retained for this trial

Endpoint Studied treat.
n/N Control treat.
n/N Graph RR [95% CI]

All cause death

115 / 640
80 / 636
1,43 [1,10;1,86]

Amputation

10 / 640
10 / 636
classic 0,99 [0,42;2,37] 0 2 1.0

Relative risks
Endpoint	Events (%)		Relative Risk	95% CI	Endpoint definition in the trial	Ref
	Studied treat.	Control treat.
All cause death	115 / 640 (18,0%)	80 / 636 (12,6%)	1,43	[1,10;1,86]	Death (any cause)	0
Amputation	10 / 640 (1,6%)	10 / 636 (1,6%)	0,99	[0,42;2,37]	Above ankle amputation for critical limb ischaemia	0
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction: 0:

Endpoint	studied treat.	control treat.	mean diff

Absolute risk reduction (for a follow-up of )
Endpoint	Events rate		Absolute risk reduction (ARR)
	Studied treat.	Control treat.
All cause death	17,97%	12,58%	5,4%
Amputation	1,56%	1,57%	-0,01%

Meta-analysis of all similar trials:

antioxydants in cardiovascular prevention for all type of patients

antioxydants in cardiovascular prevention for diabetic patients

antioxydants in diabetes type 2 for all type of patients

antioxydants in peripheral vascular diseases for diabetic patients

antioxydants in peripheral vascular diseases for all type of patients

Reference(s)

TrialResults-center ID	TRC8776
Trials register #	ISRCTN53295293

• Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, Macfarlane P, Morris A, Jung R, Kelly C, Connacher A, Peden N, Jamieson A, Matthews D, Leese G, McKnight J, O'Brien I, Semple C, Petrie J, Gordon D, . The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease.. BMJ 2008 Oct 16;337:a1840
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