Delving into the Latest Updates on Chlorthalidone with Synapse

Overview

Basic Info

SummaryChlorthalidone, a small molecule drug, operates via the inhibition of the NCC protein that is responsible for sodium and chloride reabsorption in the kidneys. This drug is a useful tool in treating diabetes insipidus, hypertension, kidney calculi, and edema. Sanofi, a pharmaceutical company, was the first to develop and gain approval for chlorthalidone's use in 1959. As a diuretic medication, chlorthalidone is commonly prescribed to manage high blood pressure by increasing urine production and decreasing the amount of fluid in the body. Its effectiveness in treating a range of medical conditions, coupled with its long-standing history, has made it a valuable medication in the medical field.

Drug Type

Small molecule drug

Synonyms

1-keto-3-(3'-sulfamyl-4'-chlorophenyl)-3-hydroxyisoindoline, 1-oxo-3-(3-sulfamyl-4-chlorophenyl)-3-hydroxyisoindoline, 2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)benzenesulfonamide

+ [16]

Target

NCC

Mechanism

NCC inhibitors(Thiazide-sensitive sodium-chloride cotransporter inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesEndocrinology and Metabolic Disease+ [2]

Active Indication

Diabetes InsipidusEdemaNephrolithiasis+ [1]

Inactive Indication-

Originator Organization

Sanofi

Active Organization

Sanofi

Chengdu First Pharmaceutical Co. Ltd.

Casper Pharma LLC

Inactive Organization

Sanofi-Aventis U.S. LLC

Drug Highest PhaseApproved

First Approval Date

CH (01 Jan 1959),

Hypertension

Regulation-

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Structure

Molecular FormulaC14H11ClN2O4S

InChIKeyJIVPVXMEBJLZRO-UHFFFAOYSA-N

CAS Registry77-36-1

High blood pressure (BP) is a public health problem worldwide. Nearly three-quarters of older adults (age
60 years) in the United States have high BP. High BP links to many health problems, like stroke. Drug treatments are typically used in clinics to reduce high BP and the risk of associated health problems. However, these drug treatments may not always benefit brain health. For example, drug treatment may reduce brain blood flow, which may reduce cognitive function in older adults with high BP. Alternatively, reduced brain blood flow may cause high BP due to increased nervous system activity (the so-called "fight or flight response"). Thus, monitoring brain blood flow may help to manage high BP during drug treatment.
It is unknown if brain blood flow and its control will be altered by drug treatment in older high BP patients. Therefore, study team will recruit older adults with high BP, who receive either drug treatment or a placebo for 2 weeks and will assess brain blood flow, cognitive function, and nervous system control before and after treatment.
Results from this study will provide novel and clinically relevant information on the impact of drug treatment for high BP on brain health. Investigators expect these results will suggest that it is crucial to measure brain blood flow, which may be a therapeutic new target for BP control and brain health.

Start Date15 May 2024

Sponsor / Collaborator

The University of Texas Southwestern Medical Center

100 Clinical Results associated with Chlorthalidone

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100 Translational Medicine associated with Chlorthalidone

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100 Patents (Medical) associated with Chlorthalidone

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1,595

Literatures (Medical) associated with Chlorthalidone

01 Mar 2024·Journal of hypertension

Use trends of chlorthalidone and hydrochlorothiazide among United States adults with hypertension: National Health and Nutrition Examination Survey 2009–2018

Article

Author: Perez, Alexandra ; El-Mcharfie, Layall ; Puchades, Emily ; Hale, Genevieve ; Jacomino, Gema

Objectives::

To estimate the national prevalence of chlorthalidone and hydrochlorothiazide use among adults diagnosed with hypertension by sociodemographic subgroup, healthcare access status, and clinical factors.

Methods::

Data was extracted from the National Health and Nutrition Examination Survey for 2009–2010 through 2017–2018 survey waves. Patients at least 20 years old, diagnosed with hypertension, and on hydrochlorothiazide or chlorthalidone were included. Uni-variable logistic regression models estimated the odds of being on chlorthalidone compared with hydrochlorothiazide use by sociodemographic and clinical factors. Analyses were adjusted for multi-stage complex survey design and are nationally representative.

Results::

Two thousand five hundred and eighty-five participants were included with 95.2% participants using hydrochlorothiazide and 4.8% using chlorthalidone. Participants over 65 years were more likely to be on chlorthalidone compared with younger counterparts [odds ratio (OR) 1.8; 95% confidence interval (CI) 1.12–2.88]. Participants with hypokalemia (OR 2.62; 95% CI 1.56–4.42) or hyponatremia [OR 2.298; 95% CI 1.23–4.30) were more likely to be using chlorthalidone compared with patients with normal levels.

Conclusion::

Chlorthalidone, a potent and effective first-line antihypertensive agent and thoroughly studied thiazide diuretic with substantial cardiovascular benefits, continues to be underutilized in patients with hypertension. Findings demonstrated that individuals receiving chlorthalidone were more likely to be 65 years or older and to experience hyponatremia or hypokalemia. Sociodemographic factors, healthcare access and use, clinical factors, and medical conditions did not appear to sway the choice in thiazide diuretic use.

01 Jan 2024·Hypertension (Dallas, Tex. : 1979)

Chlorthalidone or Spironolactone for Patients With TRH and Advanced Chronic Kidney Disease?

Article

Author: Auchus, Richard J ; Pitt, Bertram

01 Jan 2024·Annales pharmaceutiques francaises

Separation and quantification of azelnidipine and chlorthalidone in a synthetic mixture using optimized HPTLC method

Article

Author: Raimalani, Juhi ; Kotadiya, Rajendra

OBJECTIVES:

A simple, accurate, and reliable high-performance thin-layer chromatographic technique has been developed and validated for the simultaneous quantitation of azelnidipine and chlorthalidone in bulk and synthetic mixtures.

MATERIAL AND METHODS:

The procedure was carried out using a precoated silica gel 60 F254 TLC plate with a mobile phase of chloroform, ethyl acetate, and methanol in the ratio of 6.5:3.5:0.6 (by volume). Thin-layer chromatographic densitometry at 240nm was used to quantify medicines chromatographically.

RESULTS:

Over concentration ranges of 250.0 to 1000.0ng/band for chlorthalidone and 160.0 to 640.0ng/band for azelnidipine, the high-performance thin-layer chromatography technique was quantitated. This technique produced a tight and well-resolved band at retention factors of 0.67±0.02 and 0.24±0.02 for azelnidipine and chlorthalidone, respectively. Data from a linear regression study calibrating this method revealed a strong linear correlation between the two approaches, with regression coefficients of r2>0.99 for both. According to The International Conference for Harmonization of Technical Requirements for Pharmaceuticals for Human Use requirements, the procedures were validated for precision, robustness, accuracy, and specificity.

CONCLUSION:

The developed method was also used to simultaneously estimate azelnidipine and chlorthalidone in a synthetic mixture. The results were found to be in exemplary % assay with label claims.

4

News (Medical) associated with Chlorthalidone

16 May 2024

·www.prnewswire.com

New Analysis on Hypertension Treatment to be Presented as Late-Breaking Research at National Kidney Foundation Spring Clinical Meetings

LONG BEACH, Calif., May 16, 2024 /PRNewswire/ -- A new analysis of a study comparing two commonly used medications, chlorthalidone (CTD) and hydrochlorothiazide (HCTZ), is set to be presented as a late-breaking presentation at the annual 2024 National Kidney Foundation Spring Clinical Meetings. Continue Reading The study, titled "Treatment with Chlorthalidone vs Hydrochlorothiazide and Renal Outcomes: The Diuretic Comparison Project (DCP)," conducted by a team of distinguished researchers from various institutions and led by Areef Ishani, MD MS, Minneapolis VA Health Care System Primary Care and Specialty Care Integrated Care Community (ICC) Director and Professor of Medicine, University of Minnesota provides crucial insights into the impact of these medications on renal health in hypertensive patients. New study comparing two commonly used medications set to be shared as a late-breaking presentation at NKF's Conference. Post this Hypertension, or high blood pressure, is a significant risk factor for the development and progression of chronic kidney disease (CKD). Previous research had hinted at potential differences in kidney outcomes between chlorthalidone and hydrochlorothiazide. This new study followed more than 12,000 participants for an average of 3.9 years. The study found no significant disparity in renal outcomes between patients treated with chlorthalidone and those treated with hydrochlorothiazide. Specifically, there was no marked difference observed in the primary composite renal outcome, including doubling of serum creatinine, a significant drop in estimated glomerular filtration rate (eGFR), or kidney failure requiring treatment (KFRT), between the two treatment groups. Furthermore, the study revealed that the total slope of eGFR change and the incidence of chronic kidney disease (CKD) were comparable between patients receiving chlorthalidone and hydrochlorothiazide, suggesting similar efficacy in preserving kidney function. The findings offer reassurance that both chlorthalidone and hydrochlorothiazide may be equally effective choices for managing hypertension without compromising renal health. About NKF Spring Clinical Meetings For the past 32 years, nephrology healthcare professionals from across the country have come to NKF's Spring Clinical Meetings to learn about the newest developments related to all aspects of nephrology practice; network with colleagues; and present their research findings. The NKF Spring Clinical Meetings is designed for meaningful change in the multidisciplinary healthcare teams' skills, performance, and patient health outcomes. It is the only conference of its kind that focuses on translating science into practice for the entire healthcare team. About Kidney Disease In the United States, more than 37 million adults are estimated to have kidney disease, also known as chronic kidney disease (CKD)—and approximately 90 percent don't know they have it. About 1 in 3 adults in the U.S. are at risk for kidney disease. Risk factors for kidney disease include: diabetes, high blood pressure, heart disease, obesity, and family history. People of Black or African American, Hispanic or Latino, American Indian or Alaska Native, Asian American, or Native Hawaiian or Other Pacific Islander descent are at increased risk for developing the disease. Black or African American people are about four times as likely as White people to have kidney failure. Hispanics experience kidney failure at about double the rate of White people. About NKF Professional Memberships Healthcare professionals can join NKF to receive access to tools and resources for both patients and professionals, discounts on professional education, and access to a network of thousands of individuals who treat patients with kidney disease. About the National Kidney Foundation The National Kidney Foundation is revolutionizing the fight to save lives by eliminating preventable kidney disease, accelerating innovation for the dignity of the patient experience, and dismantling structural inequities in kidney care, dialysis, and transplantation. NKF Website Instagram Facebook X SOURCE The National Kidney Foundation

Clinical Study

15 Dec 2022

·www.sciencedaily.com

New study method finds two blood pressure drugs equally effective

A clinical trial found that two first-line treatments for high blood pressure were equally effective. A large VA clinical trial found that the blood pressure drug chlorthalidone (CTD) was not superior to hydrochlorothiazide (HCTZ) for the prevention of cardiovascular disease or non-cancer death. Both drugs are in a class of medications called thiazide diuretics, commonly known as water pills. They are used to help the body rid itself of excess fluid, which can lower blood pressure. The study was a first-of-its-kind pragmatic trial that was embedded in usual clinical care. As part of VA's clinical trials enterprise, it allowed participation from across the country with no additional staff. Also, all study procedures were done as part of routine clinical care. There was no additional burden placed on Veterans who participated in the study, including no extra visits. "Because of the number of Veterans VA cares for and our systemwide electronic medical record, we were able to embed this massive clinical trial within day-to-day care without any additional burden to the thousands of Veterans who volunteered for this study," said Rachel Ramoni, VA's chief research and development officer. "The result is important evidence of how these widely-used medications work in the real world." Current clinical guidelines say that CTD may be more effective than HCTZ to lower blood pressure, but this recommendation is unsupported by direct evidence. Both medications have been used for more than 50 years and each is considered a first-line treatment for hypertension. "In 2020, Medicare reported that approximately 1.5 million people were prescribed CTD compared to 11.5 million prescribed HCTZ, despite guideline recommendations," said principal investigator Dr. Areef Ishani, director of the Minneapolis VA Health Care System's Primary Care and Specialty Care Integrated Care Community. "This discrepancy between clinical guidelines and real-world usage is possibly related to the belief that CTD has a greater risk of adverse effects without clear evidence for differences in cardiovascular outcomes." The Diuretic Comparison Project (CSP 597) is a large pragmatic clinical trial that was conducted at 537 VA medical centers and community clinics in the U.S. The trial enrolled more than 4,000 providers and 13,500 Veterans with high blood pressure who were taking HCTZ at baseline. Study participants were randomized to stay on their current dose of HCTZ or take an equivalent dose of CTD. Ninety-five percent of study participants were taking a lower dose of HCTZ, so the main study comparison was 12.5 mg CTD to 25 mg HCTZ. The team found no difference between the two drugs, at these lower doses, for the prevention of cardiovascular disease or non-cancer death, which included heart attack, stroke, heart failure, or lack of blood flow requiring medical intervention. There was a slight increase in the risk for low potassium in the CTD group, which quickly resolved with potassium supplements. "We were able to compare two commonly prescribed generic drugs using a low-cost methodology," said Ishani. "This trial has shown that large, embedded trials are operationally feasible. They can be incorporated into the clinical workflow of providers by leveraging the electronic health record and other existing infrastructure." The study was funded by the VA Cooperative Studies Program. The study results were published online December 14, 2022, by the New England Journal of Medicine.

Clinical ResultAHAClinical Study

02 Mar 2020

·www.bioportfolio.com

AstraZeneca completes divestment agreement with Atnahs Pharma for established hypertension medicines

AstraZeneca today announced that it has completed the previously communicated agreement with Atnahs Pharma (Atnahs) to divest its global commercial rights to Inderal (propranolol), Tenormin (atenolol), Tenoretic (atenolol, chlorthalidone fixed-dose combination), Zestril (lisinopril) and Zestoretic (lisinopril, hydrochlorothiazide fixed-dose combination).

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100 Deals associated with Chlorthalidone

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External Link

KEGG	Wiki	ATC	Drug Bank
D00272	Chlorthalidone	C03BA04	DB00310

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetes Insipidus	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1985
Edema	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1985
Nephrolithiasis	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1985
Hypertension	CH	Sanofi	01 Jan 1959

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02665117 (CTgov)	Not Applicable	Hypertension	61	KMgCit+Potassium Magnesium Citrate (KMgCit)+chlorthalidone (KMgCit + Chlorthalidone)	bftbqzdynt(dpfbpokaay) = pxnkplhocc xjrpkcjgph (ppopkntsgm, ymkvwdqjms - kmbrygsrrs) View more	-	25 Oct 2023
				Potassium Chloride (KCl)+chlorthalidone (KCl + Chlorthalidone)	bftbqzdynt(dpfbpokaay) = injqgsthxp xjrpkcjgph (ppopkntsgm, ozbagowpoz - vvkmgngbwz) View more
NCT02185417 (Pubmed \| Br Dent J)	Phase 3	Hypertension	13,523	Chlorthalidone	laahpfvwkc(csuouhrezp) = The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P<0.001) visfjioqoo (eqretzjxhz ) View more	Negative	14 Dec 2022
				Hydrochlorothiazide
NCT02841280 (CTgov)	Phase 2	Chronic Kidney Diseases \| Hypertension	160	Chlorthalidone (Chlorthalidone)	mhhmnusrto(cdjnhqbpiz) = uoavtxxnan iimixeluwo (jkdhfnbtay, rrwmigtmwc - yivbsaocem) View more	-	31 Mar 2022
				Placebo (Placebo)	mhhmnusrto(cdjnhqbpiz) = fwprbkqekr iimixeluwo (jkdhfnbtay, mkmdwshmcc - ubaqorcloc) View more
NCT02841280 (Pubmed) Manual	Phase 2	Hypertension \| Chronic Kidney Diseases	160	Chlorthalidone	buaubctrrx(lgqqsflfsv) = jbkjmlbamz lfspssnmkz (gnfxwmbfgm, -13.9 ~ -8.1)	Positive	05 Nov 2021
				Placebo	buaubctrrx(lgqqsflfsv) = nagaxbkfqm lfspssnmkz (gnfxwmbfgm, -3.5 ~ 2.5)
NCT03325114 (CTgov)	Phase 2	Hypercalciuria \| Diabetes Mellitus, Type 1	1	chlorthalidone	dzqzuuczdy(tjjjotqttl) = tbhvpwmzer fhxfnykcph (ncoycdzytc, fohmhzetfb - ezqbxhzbhp) View more	-	05 Jan 2021
HEBE Trial (ASN2020)	Phase 4	Chronic Kidney Diseases	-	Bumetanide 2 mg BID + Chlorthalidone 50 mg BID	gaytsdgubw(ghatzlrdhb) = nfolltfmcs vnzvildcsk (nvshezorgh, 10.7) View more	Positive	19 Oct 2020
				Bumetanide 2 mg BID + Placebo	gaytsdgubw(ghatzlrdhb) = gvtksjfwfb vnzvildcsk (nvshezorgh, 11.9) View more
NCT04393493 (CTgov)	Phase 2	Cardio-Renal Syndrome	80	Furosemide (Stepped Furosemide)	qytjuwnyor(xylmisinvv) = uhbrtypwgv nhctfhtzdb (noshhqmsou, wmwnjbrvku - ntidwptunm) View more	-	14 Sep 2020
				Spironolactone+Furosemide+Chlortalidone (Diuretics Combined)	qytjuwnyor(xylmisinvv) = dxpvmgsvie nhctfhtzdb (noshhqmsou, tbsbiheybo - lmmjgqhsxg) View more
HEBE-CKD Trial (ESC2020)	Not Applicable	Chronic Kidney Diseases	-	Bumetanide + Chlorthalidone	gchlytsyhw(dzbrbwnjhr) = yuwfvheghj fykiygfesv (vfyvihxgys ) View more	Positive	30 Aug 2020
				Bumetanide + Placebo	gchlytsyhw(dzbrbwnjhr) = gtcckvtktv fykiygfesv (vfyvihxgys ) View more
NCT03923933 (CTgov)	Phase 2	Chronic Kidney Diseases	34	Bumetanide (Placebo)	xboxvismvd(hqsjehxaqo) = qodcbyhpux kptgvgekbw (wcawdijhsp, sgfeetqyxf - gwlgbigwbp) View more	-	10 Mar 2020
				Bumetanide+Chlorthalidone (Treatment Grup)	xboxvismvd(hqsjehxaqo) = uewnjmifwc kptgvgekbw (wcawdijhsp, ujgddyrzrq - zrgbvymsxs) View more
ASN2019	Not Applicable	-	113	KCl	jhjqycjbpy(ufffzuitll) = mdgtryhopi vtyngjvesj (doxrktxzel, 0.2) View more	Positive	05 Nov 2019
				KCit	jzjzsxuhze(lzrggupiwb) = djflhunoah sksfsfadsh (wnlteqwbcr, 0.3)