Gouranga Sarkar1, Vijay B Gaikwad2, Aradhana Sharma3, Swapan K Halder4, Darivemula A Kumar5, Jitendra Anand6, Sumit Agrawal7, Avinash Kumbhar8, Bhushan Kinholkar9, Rishabh Mathur10, Maulik Doshi11, Deepak Bachani12, Suyog Mehta13. 1. Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India. 2. Government Medical College, Aurangabad, Maharashtra, India. 3. SMS Medical College and Hospital, Jaipur, Rajasthan, India. 4. NRS Medical College and Hospital, Kolkata, West Bengal, India. 5. Gandhi Hospital, Secunderabad, Telangana, India. 6. Kanoria Hospital and Research Centre, Gandhinagar, Gujarat, India. 7. Oyster and Pearl Hospital, Pune, Maharashtra, India. 8. Aster Aadhar Hospital (Prerana Hospital Ltd.), Kolhapur, Maharashtra, India. 9. Sanjeevan Hospital, Pune, Maharashtra, India. 10. Marudhar Hospital, Jaipur, Rajasthan, India. 11. India Clinical Research, Sun Pharma, Mumbai, India. 12. India Medical Affairs, Sun Pharma, Mumbai, Maharashtra, India. Deepak.Bachani@sunpharma.com. 13. India Medical Affairs, Sun Pharma, Mumbai, Maharashtra, India.
Abstract
INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of metoprolol, telmisartan, and chlorthalidone in patients with essential hypertension and stable coronary artery disease (CAD) who showed inadequate response to dual therapy. METHODS: In this phase III, open-label, multicenter study, 254 adults with stable CAD having uncontrolled hypertension despite being treated with FDC of metoprolol (25/50 mg) and telmisartan (40 mg) were included. Patients received either of the following FDC for 24 weeks: metoprolol (25 mg), telmisartan (40 mg), and chlorthalidone (12.5 mg) (FDC1; n = 139) or metoprolol (50 mg), telmisartan (40 mg), and chlorthalidone (12.5 mg) (FDC2; n = 115) tablets once daily. The FDCs were developed using the novel Wrap Matrix™ platform technology. Primary endpoint assessed the mean change in seated diastolic blood pressure (SeDBP) and seated systolic blood pressure (SeSBP) from baseline to 24 weeks. Secondary efficacy endpoints included proportion of patients achieving < 90 mmHg SeDBP (SeDBP responder) and < 140 mmHg SeSBP (SeSBP responder) at weeks 12, 16, 20, and 24. Safety was assessed throughout the study. RESULTS: A total of 243 (95.70%) patients completed study. The mean change in BP from baseline (FDC1, 155/96 mmHg; FDC2, 165/98 mmHg) to week 24 (FDC1, 128/82 mmHg; FDC2, 131/83 mmHg) was statistically significant (both groups p < 0.0001). Within FDC1 and FDC2, the mean change from baseline to week 24 in SeDBP (82.60 mmHg and 83.09 mmHg) and SeSBP (128.07 mmHg and 131.29 mmHg) was statistically significant (both groups p < 0.0001). At week 24, in FDC1, 80.15% and 84.73% were SeDBP and SeSBP responders, respectively; in FDC2, 79.46% and 74.11% were SeDBP and SeSBP responders, respectively. No serious adverse events or deaths were reported. CONCLUSION: Triple FDCs of metoprolol, telmisartan, and chlorthalidone were considered effective and well tolerated in patients with hypertension who respond inadequately to dual therapy. CLINICAL TRIAL REGISTRATION: CTRI/2016/11/007491.
INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of metoprolol, telmisartan, and chlorthalidone in patients with essential hypertension and stable coronary artery disease (CAD) who showed inadequate response to dual therapy. METHODS: In this phase III, open-label, multicenter study, 254 adults with stable CAD having uncontrolled hypertension despite being treated with FDC of metoprolol (25/50 mg) and telmisartan (40 mg) were included. Patients received either of the following FDC for 24 weeks: metoprolol (25 mg), telmisartan (40 mg), and chlorthalidone (12.5 mg) (FDC1; n = 139) or metoprolol (50 mg), telmisartan (40 mg), and chlorthalidone (12.5 mg) (FDC2; n = 115) tablets once daily. The FDCs were developed using the novel Wrap Matrix™ platform technology. Primary endpoint assessed the mean change in seated diastolic blood pressure (SeDBP) and seated systolic blood pressure (SeSBP) from baseline to 24 weeks. Secondary efficacy endpoints included proportion of patients achieving < 90 mmHg SeDBP (SeDBP responder) and < 140 mmHg SeSBP (SeSBP responder) at weeks 12, 16, 20, and 24. Safety was assessed throughout the study. RESULTS: A total of 243 (95.70%) patients completed study. The mean change in BP from baseline (FDC1, 155/96 mmHg; FDC2, 165/98 mmHg) to week 24 (FDC1, 128/82 mmHg; FDC2, 131/83 mmHg) was statistically significant (both groups p < 0.0001). Within FDC1 and FDC2, the mean change from baseline to week 24 in SeDBP (82.60 mmHg and 83.09 mmHg) and SeSBP (128.07 mmHg and 131.29 mmHg) was statistically significant (both groups p < 0.0001). At week 24, in FDC1, 80.15% and 84.73% were SeDBP and SeSBP responders, respectively; in FDC2, 79.46% and 74.11% were SeDBP and SeSBP responders, respectively. No serious adverse events or deaths were reported. CONCLUSION: Triple FDCs of metoprolol, telmisartan, and chlorthalidone were considered effective and well tolerated in patients with hypertension who respond inadequately to dual therapy. CLINICAL TRIAL REGISTRATION: CTRI/2016/11/007491.
Authors: Henry R Black; William J Elliott; Gregory Grandits; Patricia Grambsch; Tracy Lucente; William B White; James D Neaton; Richard H Grimm; Lennart Hansson; Yves Lacourciere; James Muller; Peter Sleight; Michael A Weber; Gordon Williams; Janet Wittes; Alberto Zanchetti; Robert J Anders Journal: JAMA Date: 2003 Apr 23-30 Impact factor: 56.272
Authors: Björn Dahlöf; Richard B Devereux; Sverre E Kjeldsen; Stevo Julius; Gareth Beevers; Ulf de Faire; Frej Fyhrquist; Hans Ibsen; Krister Kristiansson; Ole Lederballe-Pedersen; Lars H Lindholm; Markku S Nieminen; Per Omvik; Suzanne Oparil; Hans Wedel Journal: Lancet Date: 2002-03-23 Impact factor: 79.321
Authors: Joshua D Bundy; Changwei Li; Patrick Stuchlik; Xiaoqing Bu; Tanika N Kelly; Katherine T Mills; Hua He; Jing Chen; Paul K Whelton; Jiang He Journal: JAMA Cardiol Date: 2017-07-01 Impact factor: 14.676
Authors: B J Materson; D J Reda; W C Cushman; B M Massie; E D Freis; M S Kochar; R J Hamburger; C Fye; R Lakshman; J Gottdiener Journal: N Engl J Med Date: 1993-04-01 Impact factor: 91.245
Authors: L Hansson; A Zanchetti; S G Carruthers; B Dahlöf; D Elmfeldt; S Julius; J Ménard; K H Rahn; H Wedel; S Westerling Journal: Lancet Date: 1998-06-13 Impact factor: 79.321
Authors: Jonas Prenissl; Jennifer Manne-Goehler; Lindsay M Jaacks; Dorairaj Prabhakaran; Ashish Awasthi; Anne Christine Bischops; Rifat Atun; Till Bärnighausen; Justine I Davies; Sebastian Vollmer; Pascal Geldsetzer Journal: PLoS Med Date: 2019-05-03 Impact factor: 11.069
Authors: Olga V Zimnitskaya; Marina M Petrova; Natalia V Lareva; Marina S Cherniaeva; Mustafa Al-Zamil; Anastasia E Ivanova; Natalia A Shnayder Journal: Genes (Basel) Date: 2022-07-12 Impact factor: 4.141