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

Chengdu First Pharmaceutical Co. Ltd.

Casper Pharma LLC

Sanofi

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

The aim of this study is to test the efficacy of the two long-acting thiazide-like diuretics indapamide and chlorthalidone in reducing urine supersaturation for calcium oxalate and calcium phosphate compared to the short-acting thiazide diuretic hydrochlorothiazide for the prevention of calcium-containing kidney stones.

Start Date01 Oct 2024

Sponsor / Collaborator

Insel Gruppe AG

[+1]

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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1,657

Literatures (Medical) associated with Chlorthalidone

01 Nov 2024·Journal of the American Pharmacists Association

Probable chlorthalidone-induced hypokalemic rhabdomyolysis

Article

Author: Singh, Gagandeep ; Langworthy, Diana ; Canton, Caitlin

OBJECTIVEA case of hypokalemic rhabdomyolysis related to chlorthalidone use is reported SUMMARY: A 52-year-old male was admitted to the hospital for acute onset generalized weakness and was found to have severe hypokalemia and rhabdomyolysis. The patient had been on chlorthalidone therapy with a dose increase from 25mg daily to 50mg daily two months prior to admission. Extensive workup ruled out neurologic, rheumatologic and endocrinologic causes of hypokalemia. In the absence of other causes, it was determined that the patient was experiencing a severe presentation of chlorthalidone-induced hypokalemia resulting in rhabdomyolysis. The patient's rhabdomyolysis and weakness improved with aggressive potassium correction, and potassium wasting eventually resolved with discontinuation of chlorthalidone.CONCLUSIONAlthough mild hypokalemia is a known side effect of thiazide and thiazide-like diuretics, health care providers should be aware of the possibility of severe manifestations of this adverse reaction, even at relatively small dose increases.

01 Nov 2024·The American Journal of Cardiology

Prevention of Heart Failure in Hypertension—the Role of Coronary Heart Disease Events Treated With Versus Without Revascularization: The ALLHAT Study

Article

Author: Kattan, Michael W ; Tereshchenko, Larisa G. ; Chen, Vincent ; Davis, Barry R ; Kapadia, Samir R ; Kapadia, Samir R. ; Kattan, Michael W. ; Tereshchenko, Larisa G ; Davis, Barry R.

In modern clinical practice, less than half of patients with new-onset heart failure (HF) undergo ischemic evaluation and only a minority undergo revascularization. We aimed to assess the proportion of the effect of hypertension (antihypertensive treatment) on incident HF to be eliminated by prevention of coronary heart disease (CHD) event treated with or without revascularization, considering possible treatment-mediator interaction. The causal mediation analysis of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) included 42,418 participants (age 66.9 ± 7.7, 35.6% black, 53.2% men). A new CHD event (myocardial infarction or angina) that occurred after randomization but before the incident HF outcome was the mediator. Incident symptomatic congestive HF (CHF) and hospitalized/fatal HF (HHF) were the primary and secondary outcomes, respectively. Logistic regression (for mediator) and Cox proportional hazards regression (for outcome) were adjusted for demographics, cardiovascular disease history, and risk factors. During a median 4.5-year follow-up, 2,785 patients developed CHF, including 2,216 HHF events. Participants who developed CHD events had twice the higher incidence rate of CHF than CHD-free (28.5 vs 13.9 events/1,000 person-years). The proportion of reference interaction indicating direct harm because of a CHD event for lisinopril (234% for CHF, 355% for HHF) and amlodipine (244% for CHF, 468% for HHF) was greater than for chlortalidone (143% for CHF, 269% for HHF). In patients with revascularized CHD events, chlortalidone and amlodipine eliminated 21% to 24% and lisinopril eliminated -45% of HHF. Antihypertensive treatment could not eliminate harm from CHD events treated without revascularization. In conclusion, the antihypertensive drugs (chlortalidone, lisinopril, and amlodipine) prevent HF not principally by preventing CHD events but by way of other pathways. HF is moderated but not mediated by CHD events. Revascularization of CHD events is paramount for HF prevention.

01 Nov 2024·Drug Testing and Analysis

Elimination profile of low‐dose chlortalidone and its detection in hair for doping analysis—Implication for unintentional non‐therapeutic exposure

Article

Author: Thieme, Detlef ; Anielski, Patricia ; Krumbholz, Aniko ; Keiler, Annekathrin M. ; Weigel, Kai ; Sporkert, Frank

AbstractChlortalidone (CLT) is a thiazide‐type diuretic with high affinity for the erythrocyte carbonic anhydrase. Therapeutically, it is mostly used to treat edema and hypertension due to liver cirrhosis, heart insufficiency, or renal dysfunction. Although diuretics and masking agents are prohibited by the World Anti‐Doping Agency (WADA) at all times in sports, substances belonging to this category are constantly detected in athlete samples, according to WADA's annual testing figures. Within this group of structurally diverse compounds, a threshold of 20 ng/mL has been introduced for six substances solely due to their presence as contaminants in other permitted drugs because of pharmaceutical production processes. In a recent presumptive doping case with a low urinary CLT concentration, the question of unintentional doping, for example, by contaminated non‐steroidal anti‐inflammatory drug intake, arose. To examine this potential scenario, a co‐elimination of low‐dose CLT and hydrochlorothiazide (HCTA; 20 × 50 μg, 0.2 mg/day each) was conducted on five consecutive days in two volunteers. Urine samples were subjected to liquid chromatography‐tandem mass spectrometry (LC–MS/MS). Moreover, we examined the incorporation of CLT in scalp hair. HCTA is rapidly excreted renally in comparatively high concentrations. In contrast, the elimination of CLT is considerably slower (terminal elimination half‐life extended by a factor of 12) and, consequently, much less concentrated in corresponding urine samples (45 and 53 ng/mL, respectively). Conversely, a higher hair incorporation of chlorthalidone was observed with simultaneous dosing of both. The results suggest that an unintentional intake of sub‐therapeutic CLT doses due to contamination might result in an adverse analytical finding.

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


NCT02841280 (CLICK, Pubmed)	Phase 2	Chronic Kidney Diseases 24-hour urinary sodium \| aldosterone \| plasma renin ... View more	160	Chlorthalidone	zwfqyebhtf(sdqgsymajn) = esovebpuhe vxauvdoyeo (lrdcovvdqy, 25.4 - 57.4) View more	Positive	12 Jun 2024
NCT02665117 (CTgov)	Not Applicable	Hypertension	61	Potassium Magnesium Citrate (KMgCit)+chlorthalidone (KMgCit + Chlorthalidone)	qlechkgrsg(mhkcyxorgj) = ddrhrhibgv bjswhrqwqr (iebdeoaeay, clbzfnxraq - zssnobrqrd) View more	-	25 Oct 2023
				Potassium Chloride (KCl)+chlorthalidone (KCl + Chlorthalidone)	qlechkgrsg(mhkcyxorgj) = ksoprhwfec bjswhrqwqr (iebdeoaeay, ehgpufuxdq - sornortzgg) View more
NCT03923933 (HEBE-CKD, Pubmed)	Phase 2	Chronic Kidney Diseases	34	Bumetanide plus chlorthalidone	cejrlosxyw(mbfclhtsey) = mfgogvqces gudjkktspm (ktpruozgoa ) View more	-	20 Sep 2022
				Bumetanide plus placebo	cejrlosxyw(mbfclhtsey) = bfvvccdocr gudjkktspm (ktpruozgoa ) View more
NCT02841280 (CLICK, CTgov)	Phase 2	Hypertension \| Chronic Kidney Diseases	160	Chlorthalidone (Chlorthalidone)	vapsyxidhi(gtzjwapnxc) = ggnamavzcy olxkzltsob (qtmhzwjyun, icynrmtckw - htshqegvny) View more	-	31 Mar 2022
				Placebo (Placebo)	vapsyxidhi(gtzjwapnxc) = vvwsmcixwx olxkzltsob (qtmhzwjyun, gvmmimosvr - asskeigidz) View more
NCT02841280 (Pubmed) Manual	Phase 2	Hypertension \| Chronic Kidney Diseases	160	Chlorthalidone	(nlzmizlbmj) = btzhrnvndc aalqoosrdw (ahuekhdyeg, -13.9 to -8.1)	Positive	05 Nov 2021
				Placebo	(nlzmizlbmj) = qgihkiztqx aalqoosrdw (ahuekhdyeg, -3.5 to 2.5)
HEBE Trial (ASN2020)	Phase 4	Chronic Kidney Diseases	-	Bumetanide 2 mg BID + Chlorthalidone 50 mg BID	(vcvjpulsne) = oplmiuijtf prlzchahjx (ogufkzcdpb, 10.7) View more	Positive	19 Oct 2020
				Bumetanide 2 mg BID + Placebo	(vcvjpulsne) = zohmnxcwdi prlzchahjx (ogufkzcdpb, 11.9) View more
NCT04393493 (CTgov)	Phase 2	Cardio-Renal Syndrome	80	Furosemide (Stepped Furosemide)	uhtcppuilz(fidxsjcqxv) = htibqbjdyf vwubtpzzos (scmutfwucg, edxcynpxfp - jqhplubbrx) View more	-	14 Sep 2020
				Spironolactone+Furosemide+Chlortalidone (Diuretics Combined)	uhtcppuilz(fidxsjcqxv) = yfhvmnvvaa vwubtpzzos (scmutfwucg, hxyjqvfvfr - mkgphvxobb) View more
HEBE-CKD Trial (ESC2020)	Not Applicable	Chronic Kidney Diseases	-	Bumetanide + Chlorthalidone	(uwmlvynqpk) = ixcqjresis gagqrnwcly (exwlximllq ) View more	Positive	30 Aug 2020
				Bumetanide + Placebo	(uwmlvynqpk) = eshdmiucee gagqrnwcly (exwlximllq ) View more
NCT03923933 (HEBE-CKD, CTgov)	Phase 2	Chronic Kidney Diseases	34	Bumetanide (Placebo)	fhobfkygwi(ikjquuymbu) = rppxqkbcds ebvixhogqv (degvzfkcdq, cnfohtcane - wvbxpkqdes) View more	-	10 Mar 2020
				Bumetanide+Chlorthalidone (Treatment Grup)	fhobfkygwi(ikjquuymbu) = qyagmsxvgb ebvixhogqv (degvzfkcdq, pepemzltyz - lyxvizzacv) View more
NCT03000608 (CTgov)	Phase 2	Plaque psoriasis	69	S-amlodipine+Chlorthalidone (SAN021 Serum)	uxfadyuddd(zgymhkbgzr) = zfotnmlupw chkpdbesem (uzxbcoctal, fjsjmpcfgz - yzkaouyalr) View more	-	29 May 2019
				SAN021 Placebo (SAN021 Placebo)	uxfadyuddd(zgymhkbgzr) = uqwcgxhwvk chkpdbesem (uzxbcoctal, rvnutkertb - apliylpqfh) View more