DIRECT: DIabetic Retinopathy Candesartan Trials.

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00252720
• Collaborator: Takeda (Industry)
• Enrollment: 1,850
• Arms: 2
• Duration (Months): 80

Study Details

Study Description

Brief Summary

The primary objective is to determine whether candesartan, compared to placebo reduces the progression of diabetic retinopathy in normotensive, normoalbuminuric type 1 diabetic patients with retinopathy.

The secondary objective is to determine whether candesartan, compared to placebo, reduces the incidence of clinically significant macular oedema (CSME) and/or proliferative diabetic retinopathy (PDR) and beneficially influences the rate of change in urinary albumin excretion rate (UAER).

This study is part of the DIRECT Programme also including a primary prevention study of diabetic retinopathy in type 1 diabetes and a secondary prevention study in type 2 diabetes. The primary objective for all three pooled studies is to determine whether candesartan, compared to placebo, reduces the incidence of microalbuminuria in type 1 and type 2 diabetic patients.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Drug: candesartan	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1850 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: DIRECT: DIabetic Retinopathy Candesartan Trials. Effects of Candesartan Cilexetil (Candesartan) on Diabetic Retinopathy in Type 1 Diabetic Patients With Retinopathy.
• Study Start Date: Aug 1, 2001
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: candesartan candesartan cilexetil 32 mg once daily	Drug: candesartan; 32 mg oral tablet; Other Names: ATACAND
No Intervention: placebo control

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a 3-step or Greater Increase in Early Treatment of Diabetic Retinopathy Study (EDTRS) Severity Scale [From baseline to end of study, i.e. 5 years, with visits after a half year, one year and thereafter one visit per year.]

   Retinopathy progression was defined as the first occurrence of at least a 3-step increase in the ETDRS severity scale. 3 steps were defined as either a 1-step change in one eye and a 2-step change in the other eye or as a 3-step change in one eye only. EDRTS is a scale with 11 steps (1-11). A generlized log-rank test was used to test difference between treatments.

Secondary Outcome Measures

1. Number of Participants With a Regression of Diabetic Retinopathy. [From baseline to the end of the study, i.e., 5 years]

   Regression of diabetic retinopathy was defined as at least a 3 step improvement or a persistent 2-step improvement (confirmed in 2 consecutive photography sets) in the Early Treatment of Diabetic Retinopathy Study (ETDRS) severity scale. 3 steps were defined as either a 1-step change in one eye and a 2-step change in the other eye or as a 3-step change in one eye only. EDRTS is a scale with 11 steps (1-11).

2. Number of Participants With Incident Clinically Significant Macular Edema (CSME) and/or Proliferative Diabetic Retinopathy (PDR). [From baseline to end of study, i.e. 5 years.]

   Clinically Significant Macular Edema (CSME) and Proliferative Diabetic Retinopathy (PDR) are diagnosed via retinal photographs.

3. Rate of Change in Urinary Albumin Excretion Rate (UAER). [From baseline to end of study, i.e. 5 years.]

   An estimate of the slope from fitting a linear regression of log (UAER) over time (post-randimisation, yearly assessments) for each patient

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female aged 18 - 55 years with type 1 diabetes diagnosed before age of 36 years and in need for continuous insulin treatment within 1 year of diagnosis of diabetes are included.

• Duration of diabetes for > 1 year and < 20 years with stable diabetic therapy within last 6 months.

• Patients with untreated resting mean sitting SBP < 130 mmHg, mean sitting DBP < 85 mmHg and with retinal photograph grading level > 20/10 up to < 47/47 (on ETDRS severity scale).

Exclusion Criteria:

• Patients with the following conditions are excluded from participation on the study:

• Cataract or media opacity of a degree which precludes taking gradable retinal photographs

• Angle closure glaucoma, which precludes pharmacological dilatation of the pupil

• History or presence of proliferative retinopathy

• History or presence of clinical significant macular oedema (CSME)

• History or evidence of photocoagulation of the retina

• Other retinal conditions which may mask assessment, eg, retinal vein occlusion

• Positive micral dipstick test

• Presence of secondary diabetes

• Pregnant or lactating women or women of child bearing potential not practicing an adequate method of contraception

• Need of treatment with ACE-inhibitor

• Haemodynamically significant aortic or mitral valve stenosis

• Known renal artery stenosis or kidney transplantation

• Hypersensitivity to study drug

• Severe concomitant disease which may interfere with the assessment of the patient, eg, malignancy, as judged by the investigator

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AstraZeneca
• Takeda

Investigators

• Study Director: AstraZeneca Atacand Medical Science Director, MD, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• CSR-D2453C00046.pdf

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00252720
• Other Study ID Numbers: D2453C00046; DIRECT; SH-AHM-0046
• First Posted: Nov 15, 2005
• Last Update Posted: Jun 3, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by AstraZeneca: Diabetes mellitus type 1
• Additional relevant MeSH terms: Retinal Diseases; Diabetic Retinopathy; Candesartan

Study Results

Participant Flow

Recruitment Details	First subject enrolled in the DIRECT programme 8 June 2001 and last subject completed the DIRECT programme 16 April 2008 mainly in hospital based clinics. The study investigators enrolled 4514 patients with type 1 diabetes to either Study 45 or 46, of whom 1905 proceeded to randomization into Study 46 (1421 into Study 45).
Pre-assignment Detail	The most common reason for not being randomized was that all eligibility criteria were not fulfilled, followed by withdrawn informed consent.

Arm/Group Title	Candesartan	Placebo
Arm/Group Description	Candesartan cilexetil 32 mg once daily	Placebo Comparator
Period Title: Overall Study
STARTED	951	954
COMPLETED	819	789
NOT COMPLETED	132	165

Baseline Characteristics

Arm/Group Title	Candesartan	Placebo	Total
Arm/Group Description	Candesartan cilexetil 32 mg once daily	Placebo Comparator	Total of all reporting groups
Overall Participants	951	954	1905
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	951 100%	954 100%	1905 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.5 (8.5)	31.9 (8.5)	31.7 (8.5)
Sex: Female, Male (Count of Participants)
Female	413 43.4%	401 42%	814 42.7%
Male	538 56.6%	553 58%	1091 57.3%
Region of Enrollment (participants) [Number]
Russian Federation	186 19.6%	162 17%	348 18.3%
Europe	595 62.6%	619 64.9%	1214 63.7%
Canada	69 7.3%	71 7.4%	140 7.3%
South Africa	101 10.6%	102 10.7%	203 10.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a 3-step or Greater Increase in Early Treatment of Diabetic Retinopathy Study (EDTRS) Severity Scale
Description	Retinopathy progression was defined as the first occurrence of at least a 3-step increase in the ETDRS severity scale. 3 steps were defined as either a 1-step change in one eye and a 2-step change in the other eye or as a 3-step change in one eye only. EDRTS is a scale with 11 steps (1-11). A generlized log-rank test was used to test difference between treatments.
Time Frame	From baseline to end of study, i.e. 5 years, with visits after a half year, one year and thereafter one visit per year.

Outcome Measure Data

Analysis Population Description

The population was the Intention to Treat population which includes all randomized patients with any post-randomization data.

Arm/Group Title	Candesartan	Placebo
Arm/Group Description	Candesartan cilexetil 32 mg once daily	Placebo Comparator
Measure Participants	951	954
Number [Participants]	127 (0.034) 13.4%	124 (0.033) 13%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Candesartan, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8487
	Comments
	Method	Log Rank
	Comments	Generalized
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.024
	Confidence Interval	(2-Sided) 95%; 0.800 to 1.312
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With a Regression of Diabetic Retinopathy.
Description	Regression of diabetic retinopathy was defined as at least a 3 step improvement or a persistent 2-step improvement (confirmed in 2 consecutive photography sets) in the Early Treatment of Diabetic Retinopathy Study (ETDRS) severity scale. 3 steps were defined as either a 1-step change in one eye and a 2-step change in the other eye or as a 3-step change in one eye only. EDRTS is a scale with 11 steps (1-11).
Time Frame	From baseline to the end of the study, i.e., 5 years

Outcome Measure Data

Analysis Population Description

The population was the Intention To Treat population which includes all randomized patients with any post-randomization data.

Arm/Group Title	Candesartan	Placebo
Arm/Group Description	Candesartan cilexetil 32 mg once daily	Placebo Comparator
Measure Participants	951	954
Number [Participants]	140 (0.039) 14.7%	139 (0.039) 14.6%

3. Secondary Outcome

Title	Number of Participants With Incident Clinically Significant Macular Edema (CSME) and/or Proliferative Diabetic Retinopathy (PDR).
Description	Clinically Significant Macular Edema (CSME) and Proliferative Diabetic Retinopathy (PDR) are diagnosed via retinal photographs.
Time Frame	From baseline to end of study, i.e. 5 years.

Outcome Measure Data

Analysis Population Description

The population was the Intention To Treat population whick includes all randomized patients with any post-randomization data.

Arm/Group Title	Candesartan	Placebo
Arm/Group Description	Candesartan cilexetil 32 mg once daily	Placebo Comparator
Measure Participants	951	954
Number [Participants]	110 (0.03) 11.6%	107 (0.03) 11.2%

4. Secondary Outcome

Title	Rate of Change in Urinary Albumin Excretion Rate (UAER).
Description	An estimate of the slope from fitting a linear regression of log (UAER) over time (post-randimisation, yearly assessments) for each patient
Time Frame	From baseline to end of study, i.e. 5 years.

Outcome Measure Data

Analysis Population Description

The population was the Intention To Treat population which includes all randimized patients with any post-randomization data.

Arm/Group Title	Candesartan	Placebo
Arm/Group Description	Candesartan cilexetil 32 mg once daily	Placebo Comparator
Measure Participants	951	954
Least Squares Mean (95% Confidence Interval) [log (µg/min)/year]	0.569	0.642

Adverse Events

Time Frame	During treatment. During Treatment refers to the period of actual treatment with randomized study drug, ie, is a subset of the patients included in During Study. During Treatment period only includes AEs reported while patients were on study treatment.
Adverse Event Reporting Description	Population used was the safety population which includes all patients who received at least 1 dose of randomized study strug and for whom any post-dose data were available.
Arm/Group Title	Candesartan		Placebo
Arm/Group Description	Candesartan cilexetil 32 mg once daily		Placebo Comparator
All Cause Mortality
	Candesartan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Candesartan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	173/951 (18.2%)		161/951 (16.9%)
Blood and lymphatic system disorders
Idiopathic Thrombocytopenic Purpura	1/951 (0.1%)		1/951 (0.1%)
Iron Deficiency Anaemia	1/951 (0.1%)		0/951 (0%)
Thrombocytopenic Purpura	1/951 (0.1%)		0/951 (0%)
Cardiac disorders
Myocardial Infarction	1/951 (0.1%)		2/951 (0.2%)
Acute Myocardial Infarction	0/951 (0%)		1/951 (0.1%)
Angina Pectoris	0/951 (0%)		1/951 (0.1%)
Cardiovascular Disorder	0/951 (0%)		1/951 (0.1%)
Congenital, familial and genetic disorders
Heart Disease Congenital	0/951 (0%)		1/951 (0.1%)
Hepato-Lenticular Degeneration	0/951 (0%)		1/951 (0.1%)
Ear and labyrinth disorders
Ear Congestion	0/951 (0%)		1/951 (0.1%)
Sudden Hearing Loss	0/951 (0%)		1/951 (0.1%)
Vestibular Neuronitis	1/951 (0.1%)		0/951 (0%)
Endocrine disorders
Addison's Disease	1/951 (0.1%)		0/951 (0%)
Eye disorders
Cataract	0/951 (0%)		1/951 (0.1%)
Conjunctivitis	1/951 (0.1%)		0/951 (0%)
Diabetic Blindness	0/951 (0%)		1/951 (0.1%)
Eye Haemorrhage	0/951 (0%)		1/951 (0.1%)
Gastrointestinal disorders
Gastritis	5/951 (0.5%)		2/951 (0.2%)
Abdominal Pain	2/951 (0.2%)		1/951 (0.1%)
Inguinal Hernia	0/951 (0%)		2/951 (0.2%)
Abdominal Adhesions	0/951 (0%)		1/951 (0.1%)
Abdominal Pain Lower	0/951 (0%)		1/951 (0.1%)
Anal Fissure	1/951 (0.1%)		0/951 (0%)
Change Of Bowel Habit	0/951 (0%)		1/951 (0.1%)
Coeliac Disease	1/951 (0.1%)		1/951 (0.1%)
Diarrhoea	0/951 (0%)		1/951 (0.1%)
Duodenal Ulcer Perforation	1/951 (0.1%)		0/951 (0%)
Dyspepsia	1/951 (0.1%)		1/951 (0.1%)
Food Poisoning	0/951 (0%)		1/951 (0.1%)
Gastric Ulcer	1/951 (0.1%)		0/951 (0%)
Gastrointestinal Haemorrhage	0/951 (0%)		1/951 (0.1%)
Gingival Disorder	0/951 (0%)		1/951 (0.1%)
Hiatus Hernia	0/951 (0%)		1/951 (0.1%)
Irritable Bowel Syndrome	1/951 (0.1%)		0/951 (0%)
Pancreatitis Acute	0/951 (0%)		1/951 (0.1%)
Rectal Polyp	0/951 (0%)		1/951 (0.1%)
Vomiting	1/951 (0.1%)		0/951 (0%)
General disorders
Chest Pain	5/951 (0.5%)		0/951 (0%)
Death	0/951 (0%)		1/951 (0.1%)
Foreign Body Reaction	0/951 (0%)		1/951 (0.1%)
Macrosomia	0/951 (0%)		1/951 (0.1%)
Oedema	1/951 (0.1%)		0/951 (0%)
Oedema Peripheral	1/951 (0.1%)		0/951 (0%)
Organ Failure	0/951 (0%)		1/951 (0.1%)
Pyrexia	0/951 (0%)		1/951 (0.1%)
Hepatobiliary disorders
Cholelithiasis	1/951 (0.1%)		1/951 (0.1%)
Hepatitis Acute	0/951 (0%)		1/951 (0.1%)
Hepatitis Toxic	0/951 (0%)		1/951 (0.1%)
Immune system disorders
Sarcoidosis	0/951 (0%)		1/951 (0.1%)
Infections and infestations
Appendicitis	4/951 (0.4%)		4/951 (0.4%)
Gastroenteritis	2/951 (0.2%)		3/951 (0.3%)
Pneumonia	3/951 (0.3%)		3/951 (0.3%)
Pyelonephritis Acute	3/951 (0.3%)		1/951 (0.1%)
Respiratory Tract Infection	3/951 (0.3%)		0/951 (0%)
Bronchitis	1/951 (0.1%)		2/951 (0.2%)
Hepatitis B	2/951 (0.2%)		0/951 (0%)
Localised Infection	2/951 (0.2%)		0/951 (0%)
Pilonidal Cyst	2/951 (0.2%)		0/951 (0%)
Postoperative Wound Infection	2/951 (0.2%)		0/951 (0%)
Pyelonephritis	0/951 (0%)		2/951 (0.2%)
Sepsis	2/951 (0.2%)		1/951 (0.1%)
Upper Respiratory Tract Infection	2/951 (0.2%)		1/951 (0.1%)
Viral Infection	1/951 (0.1%)		2/951 (0.2%)
Abdominal Abscess	0/951 (0%)		1/951 (0.1%)
Abdominal Wall Abscess	1/951 (0.1%)		0/951 (0%)
Abscess	1/951 (0.1%)		0/951 (0%)
Abscess Limb	0/951 (0%)		1/951 (0.1%)
Acute Tonsillitis	0/951 (0%)		1/951 (0.1%)
Adnexitis	1/951 (0.1%)		0/951 (0%)
Bronchopneumonia	1/951 (0.1%)		0/951 (0%)
Carbuncle	1/951 (0.1%)		0/951 (0%)
Cellulitis	1/951 (0.1%)		1/951 (0.1%)
Corneal Infection	0/951 (0%)		1/951 (0.1%)
Empyema	1/951 (0.1%)		0/951 (0%)
Encephalitis Viral	0/951 (0%)		1/951 (0.1%)
Gastrointestinal Infection	0/951 (0%)		1/951 (0.1%)
Groin Abscess	1/951 (0.1%)		0/951 (0%)
Hepatitis A	1/951 (0.1%)		0/951 (0%)
Hepatitis C	1/951 (0.1%)		0/951 (0%)
Herpes Zoster	0/951 (0%)		1/951 (0.1%)
Infected Cyst	1/951 (0.1%)		0/951 (0%)
Liver Abscess	0/951 (0%)		1/951 (0.1%)
Lower Respiratory Tract Infection	1/951 (0.1%)		1/951 (0.1%)
Oophoritis	0/951 (0%)		1/951 (0.1%)
Osteomyelitis	1/951 (0.1%)		1/951 (0.1%)
Pelvic Inflammatory Disease	0/951 (0%)		1/951 (0.1%)
Perianal Abscess	1/951 (0.1%)		1/951 (0.1%)
Perineal Abscess	1/951 (0.1%)		0/951 (0%)
Peritonsillar Abscess	1/951 (0.1%)		1/951 (0.1%)
Pulmonary Tuberculosis	1/951 (0.1%)		0/951 (0%)
Pyelonephritis Chronic	0/951 (0%)		1/951 (0.1%)
Retroperitoneal Abscess	0/951 (0%)		1/951 (0.1%)
Subcutaneous Abscess	0/951 (0%)		1/951 (0.1%)
Viral Diarrhoea	1/951 (0.1%)		0/951 (0%)
Viral Skin Infection	0/951 (0%)		1/951 (0.1%)
Wound Infection Staphylococcal	1/951 (0.1%)		0/951 (0%)
Injury, poisoning and procedural complications
Road Traffic Accident	4/951 (0.4%)		2/951 (0.2%)
Meniscus Lesion	0/951 (0%)		3/951 (0.3%)
Multiple Injuries	2/951 (0.2%)		3/951 (0.3%)
Hand Fracture	2/951 (0.2%)		1/951 (0.1%)
Humerus Fracture	2/951 (0.2%)		0/951 (0%)
Ligament Injury	0/951 (0%)		2/951 (0.2%)
Lower Limb Fracture	2/951 (0.2%)		2/951 (0.2%)
Overdose	1/951 (0.1%)		2/951 (0.2%)
Accidental Overdose	0/951 (0%)		1/951 (0.1%)
Ankle Fracture	1/951 (0.1%)		0/951 (0%)
Cartilage Injury	1/951 (0.1%)		1/951 (0.1%)
Cervical Vertebral Fracture	1/951 (0.1%)		0/951 (0%)
Concussion	0/951 (0%)		1/951 (0.1%)
Contusion	0/951 (0%)		1/951 (0.1%)
Epicondylitis	0/951 (0%)		1/951 (0.1%)
Femur Fracture	1/951 (0.1%)		0/951 (0%)
Foot Fracture	1/951 (0.1%)		0/951 (0%)
Frostbite	0/951 (0%)		1/951 (0.1%)
Gun Shot Wound	1/951 (0.1%)		0/951 (0%)
Hip Fracture	1/951 (0.1%)		0/951 (0%)
Injury Corneal	0/951 (0%)		1/951 (0.1%)
Intentional Overdose	1/951 (0.1%)		0/951 (0%)
Intervertebral Disc Injury	1/951 (0.1%)		0/951 (0%)
Joint Dislocation	1/951 (0.1%)		0/951 (0%)
Joint Injury	0/951 (0%)		1/951 (0.1%)
Ligament Rupture	1/951 (0.1%)		0/951 (0%)
Limb Injury	1/951 (0.1%)		0/951 (0%)
Multiple Fractures	0/951 (0%)		1/951 (0.1%)
Patella Fracture	0/951 (0%)		1/951 (0.1%)
Radius Fracture	1/951 (0.1%)		0/951 (0%)
Skin Laceration	0/951 (0%)		1/951 (0.1%)
Skull Fractured Base	1/951 (0.1%)		0/951 (0%)
Sports Injury	1/951 (0.1%)		0/951 (0%)
Tendon Injury	1/951 (0.1%)		0/951 (0%)
Thermal Burn	0/951 (0%)		1/951 (0.1%)
Tibia Fracture	1/951 (0.1%)		0/951 (0%)
Investigations
Hepatitis C Positive	0/951 (0%)		1/951 (0.1%)
Tumour Marker Increased	0/951 (0%)		1/951 (0.1%)
Metabolism and nutrition disorders
Diabetic Ketoacidosis	26/951 (2.7%)		17/951 (1.8%)
Hypoglycaemia	16/951 (1.7%)		24/951 (2.5%)
Hyperglycaemia	8/951 (0.8%)		13/951 (1.4%)
Diabetes Mellitus Inadequate Control	11/951 (1.2%)		8/951 (0.8%)
Ketoacidosis	1/951 (0.1%)		6/951 (0.6%)
Hypoglycaemic Seizure	4/951 (0.4%)		0/951 (0%)
Dehydration	1/951 (0.1%)		1/951 (0.1%)
Diabetic Foot	1/951 (0.1%)		0/951 (0%)
Musculoskeletal and connective tissue disorders
Periarthritis	4/951 (0.4%)		1/951 (0.1%)
Intervertebral Disc Protrusion	0/951 (0%)		3/951 (0.3%)
Musculoskeletal Chest Pain	2/951 (0.2%)		0/951 (0%)
Osteoarthritis	0/951 (0%)		2/951 (0.2%)
Arthralgia	1/951 (0.1%)		0/951 (0%)
Arthritis	0/951 (0%)		1/951 (0.1%)
Dupuytren's Contracture	1/951 (0.1%)		0/951 (0%)
Myopathy	0/951 (0%)		1/951 (0.1%)
Osteoarthropathy	1/951 (0.1%)		0/951 (0%)
Rotator Cuff Syndrome	0/951 (0%)		1/951 (0.1%)
Spondylolisthesis	1/951 (0.1%)		0/951 (0%)
Tenosynovitis	0/951 (0%)		1/951 (0.1%)
Trigger Finger	1/951 (0.1%)		1/951 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma Of Breast	0/951 (0%)		2/951 (0.2%)
Malignant Melanoma	2/951 (0.2%)		0/951 (0%)
Anaplastic Astrocytoma	1/951 (0.1%)		0/951 (0%)
Benign Colonic Neoplasm	0/951 (0%)		1/951 (0.1%)
Fibroma	1/951 (0.1%)		0/951 (0%)
Hepatic Adenoma	1/951 (0.1%)		0/951 (0%)
Lymphoma	1/951 (0.1%)		0/951 (0%)
Ovarian Adenoma	0/951 (0%)		1/951 (0.1%)
Papillary Thyroid Cancer	1/951 (0.1%)		0/951 (0%)
Penile Wart	0/951 (0%)		1/951 (0.1%)
Uterine Leiomyoma	0/951 (0%)		1/951 (0.1%)
Nervous system disorders
Hypoglycaemic Coma	3/951 (0.3%)		5/951 (0.5%)
Carpal Tunnel Syndrome	4/951 (0.4%)		1/951 (0.1%)
Diabetic Coma	2/951 (0.2%)		0/951 (0%)
Diabetic Neuropathy	0/951 (0%)		2/951 (0.2%)
Grand Mal Convulsion	2/951 (0.2%)		1/951 (0.1%)
Amnesia	1/951 (0.1%)		0/951 (0%)
Cerebral Haemorrhage	1/951 (0.1%)		0/951 (0%)
Cerebrovascular Accident	1/951 (0.1%)		1/951 (0.1%)
Diabetic Hyperosmolar Coma	1/951 (0.1%)		0/951 (0%)
Diabetic Ketoacidotic Hyperglycaemic Coma	0/951 (0%)		1/951 (0.1%)
Dizziness	0/951 (0%)		1/951 (0.1%)
Encephalopathy	1/951 (0.1%)		0/951 (0%)
Haemorrhagic Stroke	0/951 (0%)		1/951 (0.1%)
Headache	0/951 (0%)		1/951 (0.1%)
Migraine	0/951 (0%)		1/951 (0.1%)
Multiple Sclerosis	1/951 (0.1%)		0/951 (0%)
Myelitis	1/951 (0.1%)		0/951 (0%)
Sciatica	0/951 (0%)		1/951 (0.1%)
Syncope	0/951 (0%)		1/951 (0.1%)
Tension Headache	0/951 (0%)		1/951 (0.1%)
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous	0/951 (0%)		1/951 (0.1%)
Foetal Cardiac Disorder	0/951 (0%)		1/951 (0.1%)
Intra-Uterine Death	1/951 (0.1%)		0/951 (0%)
Polyhydramnios	0/951 (0%)		1/951 (0.1%)
Psychiatric disorders
Depression	1/951 (0.1%)		1/951 (0.1%)
Major Depression	0/951 (0%)		1/951 (0.1%)
Suicide Attempt	0/951 (0%)		1/951 (0.1%)
Renal and urinary disorders
Nephrolithiasis	2/951 (0.2%)		0/951 (0%)
Calculus Urinary	1/951 (0.1%)		0/951 (0%)
Diabetic Nephropathy	0/951 (0%)		1/951 (0.1%)
Haematuria	1/951 (0.1%)		0/951 (0%)
Renal Failure	0/951 (0%)		1/951 (0.1%)
Ureteric Stenosis	0/951 (0%)		1/951 (0.1%)
Reproductive system and breast disorders
Adenomyosis	0/951 (0%)		2/951 (0.2%)
Cervical Dysplasia	1/951 (0.1%)		0/951 (0%)
Dysfunctional Uterine Bleeding	0/951 (0%)		1/951 (0.1%)
Endometriosis	1/951 (0.1%)		0/951 (0%)
Menometrorrhagia	1/951 (0.1%)		0/951 (0%)
Menorrhagia	1/951 (0.1%)		1/951 (0.1%)
Ovarian Cyst	0/951 (0%)		1/951 (0.1%)
Pelvic Pain	0/951 (0%)		1/951 (0.1%)
Uterine Polyp	1/951 (0.1%)		0/951 (0%)
Varicocele	1/951 (0.1%)		0/951 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchitis Chronic	0/951 (0%)		1/951 (0.1%)
Chronic Obstructive Pulmonary Disease	0/951 (0%)		1/951 (0.1%)
Haemoptysis	0/951 (0%)		1/951 (0.1%)
Nasal Congestion	1/951 (0.1%)		0/951 (0%)
Nasal Polyps	1/951 (0.1%)		0/951 (0%)
Nasal Septum Deviation	1/951 (0.1%)		0/951 (0%)
Pneumomediastinum	1/951 (0.1%)		0/951 (0%)
Tonsillar Hypertrophy	1/951 (0.1%)		0/951 (0%)
Vocal Cord Polyp	1/951 (0.1%)		0/951 (0%)
Skin and subcutaneous tissue disorders
Angioedema	1/951 (0.1%)		0/951 (0%)
Dermal Cyst	1/951 (0.1%)		0/951 (0%)
Erythema Nodosum	1/951 (0.1%)		0/951 (0%)
Skin Ulcer	1/951 (0.1%)		0/951 (0%)
Urticaria	0/951 (0%)		1/951 (0.1%)
Vascular disorders
Hypotension	2/951 (0.2%)		1/951 (0.1%)
Femoral Artery Occlusion	0/951 (0%)		1/951 (0.1%)
Hypertension	1/951 (0.1%)		0/951 (0%)
Thrombosis	0/951 (0%)		1/951 (0.1%)
Varicose Vein	0/951 (0%)		1/951 (0.1%)
Other (Not Including Serious) Adverse Events
	Candesartan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	92/951 (9.7%)		32/951 (3.4%)
Vascular disorders
Hypotension	92/951 (9.7%)		32/951 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.