Efficacy and Safety of Losartan/Chlorthalidone vs Losartan/Hydrochlorothiazide in Essential Arterial Hypertension

Essential Arterial Hypertension Clinical Trial

Official title:

Confirmatory Study of the Efficacy and Safety of the Combination of Losartan / Chlorthalidone vs Losartan / Hydrochlorothiazide in the Treatment of Patients With Essential Arterial Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04927299
• Other study ID #: SIL-30601-III-20(1)
• Status: Completed
• Phase: Phase 3
• Start date: June 30, 2022
• Est. completion date: September 11, 2023

Study information

• Verified date: April 2024
• Source: Laboratorios Silanes S.A. de C.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase IIIb, randomized, double-blind, prospective, multicenter study to evaluate the efficacy and safety of the fixed-dose combination of losartan / chlorthalidone compared with losartan / hydrochlorothiazide in the treatment of patients with essential arterial hypertension.

Description:

Two groups of patients will be formed, who wil start treatment with the lower dose (Losartan 50 mg + chlorthalidone 12.5 mg; Losartan 50 mg + hydrochlorothiazide 12.5 mg).

Blood pressure (BP) figures will be evaluated and, in those patients who do not reach the therapeutic goal, defined as a decrease in Systolic blood pressure (SBP) / Diastolic blood pressure (DBP) values of 20/10 mmHg with respect to their baseline values or BP <140 / 90 mmHg, the dose will be escalated to the next available concentration for both treatments (Losartan 100 mg + chlorthalidone 25 mg; Losartan 100 mg + hydrochlorothiazide 25 mg) at 30 days or during an unscheduled visit.

After two months of treatment, the BP figures obtained with the final dose and the proportion of subjects who achieved a decrease in SBP / DBP values of 20/10 mmHg or <140/90 mmHg with respect to both combinations will be compared, and the frequency of adverse events presented will be described.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: September 11, 2023
• Est. primary completion date: August 15, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Any sex.

• That they agree to participate in the study and give their informed consent in writing.

• Age between 18 and 65 years old at the beginning of the study.

• Patients with essential arterial hypertension with BP =140 / 90 mmHg and <180/110 mmHg.

• Women of childbearing potential using a contraceptive method (barrier, oral hormonal, injectable, subdermal), menopausal or surgically sterile.

Exclusion Criteria:

• The drug is contraindicated for medical reasons.

• Glomerular filtration rate =30 ml / min x 1.73 m2.

• Hypersensitivity to any of the components of the formula or other sulfonamides.

• Patients treated with other diuretics.

• Patient with a history of vascular disease (cerebrovascular disease, acute coronary syndrome, etc.) and acute renal failure in the last 6 months.

• Patient with severe complications of type 2 diabetes mellitus (Ketoacidosis or hyperosmolar nonketotic coma).

• Patients participating in another clinical study involving an investigational treatment or participated in one in the previous 4 weeks.

• Positive pregnancy test, women who are pregnant, breastfeeding or planning a pregnancy while conducting the study.

• Oncological patients (except basal cell skin cancer) or with serious diseases that, in the opinion of the investigator, have a serious prognosis or a life expectancy of less than 1 year, as well as mental illnesses.

• Patients diagnosed with gout.

• Patients whose participation in the study may be influenced (employment relationship with the research center or sponsor, inmates, etc.).

Related Conditions & MeSH terms

• Essential Arterial Hypertension
• Hypertension

Intervention

Drug:
• Losartan/Chlorthalidone in fixed dose
1 tablet, once a day of 50 mg/12.5 or 100 mg/ 25 mg
• Losartan + hydrochlorothiazide in fixed dose
1 tablet, once a day of 50 mg/12.5 or 100 mg/ 25 mg

Locations

Country	Name	City	State
Mexico	Laboratorio Silanes, S.A. de C.V.	Mexico City

Sponsors (1)

Lead Sponsor	Collaborator
Laboratorios Silanes S.A. de C.V.

Country where clinical trial is conducted

Mexico, 

References & Publications (11)

2018 ESC/ESH Guidelines for the management of arterial hypertension. Rev Esp Cardiol (Engl Ed). 2019 Feb;72(2):160. doi: 10.1016/j.rec.2018.12.004. No abstract available. English, Spanish. — View Citation

ACCORD Study Group; Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HC, Ismail-Beigi F. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85. doi: 10.1056/NEJMoa1001286. Epub 2010 Mar 14. — View Citation

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72. doi: 10.1001/jama.289.19.2560. Epub 2003 May 14. Erratum In: JAMA. 2003 Jul 9;290(2):197. — View Citation

Ernst ME, Moser M. Use of diuretics in patients with hypertension. N Engl J Med. 2009 Nov 26;361(22):2153-64. doi: 10.1056/NEJMra0907219. No abstract available. Erratum In: N Engl J Med. 2010 Nov 4;363(19):1877. — View Citation

Gonzalez-Juanatey JR, Mazon Ramos P. Cardiovascular prevention (VI). Use of drugs in the primary prevention of arterial hypertension and dyslipidemia. Rev Esp Cardiol. 2008 Aug;61(8):861-79. English, Spanish. — View Citation

Guerrero-Garcia C, Rubio-Guerra AF. Combination therapy in the treatment of hypertension. Drugs Context. 2018 Jun 6;7:212531. doi: 10.7573/dic.212531. eCollection 2018. — View Citation

Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23. doi: 10.1016/S0140-6736(05)17741-1. — View Citation

Kurtz TW, Klein U. Next generation multifunctional angiotensin receptor blockers. Hypertens Res. 2009 Oct;32(10):826-34. doi: 10.1038/hr.2009.135. Epub 2009 Aug 28. — View Citation

Morales-Salinas A, Wyss F, Coca A, Ramirez AJ, Valdez O, Valerio LF. [Differences between the 2013 and 2014 hypertension guidelines.: Position of the Central American and Caribbean Society for Hypertension and Cardiovascular Prevention]. Rev Panam Salud Publica. 2015 Mar;37(3):172-8. Spanish. — View Citation

Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, Ramirez A, Schlaich M, Stergiou GS, Tomaszewski M, Wainford RD, Williams B, Schutte AE. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. 2020 Jun;75(6):1334-1357. doi: 10.1161/HYPERTENSIONAHA.120.15026. Epub 2020 May 6. No abstract available. — View Citation

Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Jun;71(6):e13-e115. doi: 10.1161/HYP.0000000000000065. Epub 2017 Nov 13. No abstract available. Erratum In: Hypertension. 2018 Jun;71(6):e140-e144. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in systolic blood pressure (SBP)	Evaluate the mean change in systolic blood pressure (SBP) at 2 months with respect to their baseline measurement, by treatment group with the final dose.	Baseline and 2 months
Primary	Change in diastolic blood pressure (DBP)	Evaluate the mean change in diastolic blood pressure (DBP) at 2 months with respect to their baseline measurement, by treatment group with the final dose.	Baseline and 2 months
Secondary	Dosage adjustment requirement	Describe the proportion of subjects who required dose adjustment per treatment group.	2 months
Secondary	Subjects who achieved blood pressure reduction goals	Proportion of subjects who decreased their systolic pressure by 20 mmHg and their diastolic pressure by 10 mmHg from baseline or blood pressure <140/90 mmHg per treatment group with the final dose.	2 months
Secondary	Percentage of adherence to treatment	Assess the percentage of adherence to treatment during the intervention, by pill count.	2 months
Secondary	Adverse events	Describe the frequency and intensity of adverse events and adverse reactions presented during the study by treatment group.	2 months

External Links

•   Official Journal of the Federation. PROJECT of Official Mexican Standard PROY-NOM-030-SSA2-2017, For the prevention, detection, diagnosis, treatment and control of systemic arterial hypertension. 2017.
•   Official Mexican NORM NOM-008-SSA3-2017, For the comprehensive treatment of overweight and obesity.