title: Optimal Combination of Effective ANtihypertensives (OCEAN) study: a prospective, randomized, open-label, blinded endpoint trial--rationale, design and results of a pilot study in Japan.
abstract: There are limited clinical trials examining the efficacy of antihypertensive drug combinations aimed at preventing cardiovascular events. Therefore, we designed a randomized controlled trial using amlodipine as the base drug of a multi-drug regimen, the Optimal Combination of Effective ANtihypertensives (OCEAN) Study, to determine the drug combination that is most efficacious in the prevention of cardiovascular events, such as stroke. The OCEAN Study is a collaborative study between Japan and China, enrolling 20 000 patients and following them for 3 to 4 years. A pilot study was conducted before the full-scale study to confirm the feasibility of the protocol and that the study groups and infrastructures could function properly. A total of 279 Japanese patients were enrolled from 57 participating medical institutions between June and December 2004. Two hundred and sixty-six patients (mean age: 65.9 years) were treated with amlodipine alone. One hundred and fifty-four of these patients (57.9%) did not reach the treatment targets (<140/90 mm Hg for the elderly and patients with cerebrovascular disease, <130/80 mm Hg for those with diabetes mellitus, chronic kidney disease or prior myocardial infarction) and a second agent was added. They were randomly allocated into three different treatment groups using a diuretic, a β-blocker or an angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist. The pilot study showed that the protocol was appropriate, and the inclusion of patients with slightly higher blood pressures was necessary to increase the randomization rate. It also confirmed that we organized properly functioning study groups and infrastructures.
authors.affiliation: Division of Clinical Pharmacology and Therapeutics, The Jikei University School of Medicine, Tokyo, Japan. kageyama@jikei.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kageyama
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ueda
authors.forename: Kouichi
authors.initials: K
authors.lastname: Mochizuki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyakawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugawara
authors.forename: Michio
authors.initials: M
authors.lastname: Nakayama
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saito
authors.forename: Takao
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007564:Japan / Q000453:epidemiology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012107:Research Design; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D008055:Lipids; D017311:Amlodipine