Multi-centre clinical investigation of indapamide in the United States: a review.

ABSTRACT

Indapamide, a new indoline antihypertensive agent, has been the subject of a worldwide programme to develop this drug for general clinical use. The results are described of the multi-centre U.S. clinical programme demonstrating the effectiveness and tolerance of indapamide for the treatment of hypertension. All work was conducted under U.S. Federal Food and Drug Administration guidelines, and resulted recently in a New Drug Application. A total of 1891 subjects or patients participated in 27 separate studies conducted by 91 investigators. In controlled clinical trials comparing 2.5 mg indapamide once daily with 50 mg hydrochlorothiazide once daily for 40 weeks in patients with mild to moderate essential hypertension, indapamide produced a reduction of supine blood pressure of -9.5/-14.3 mmHg as compared with -7.6/-11.4 mmHg for hydrochlorothiazide. In combination with methyldopa, propranolol, clonidine, guanethidine and hydralazine, indapamide consistently produced a greater decrease in arterial pressure than did those agents given alone. Indapamide added to these step-care agents did not result in a meaningful increase in adverse reactions. Indapamide has been the subject of a long-term safety study in which over 100 hypertensive patients have been followed up for 2 years or longer. During this period of time, indapamide was well tolerated and remained effective. No biochemical, electrocardiographic or ophthalmological changes were associated with its use. Other studies with indapamide are discussed describing the systemic and renal haemodynamic effects, pharmacokinetic properties and special safety studies conducted with this agent. The use of indapamide in patients with hepatic or renal impairment is reviewed in detail.