Summary
Chlorthalidone has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Hypertension would be drug repurposing rather than first-in-human development. This does not mean it is approved for Hypertension. ClinicalTrials.gov lists 8 registered trials linking Chlorthalidone to Hypertension: 1 is active or not yet recruiting; 6 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT00695955). The largest enrolment is 1219 participants (NCT06282549). Registration activity spans 2007 to 2022. The literature layer holds 16 publications for this pair: 4 Cochrane reviews, 3 meta-analyses, 4 systematic reviews and 5 clinical trial publications. Publication years run from 2012 to 2026. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Essential Hypertension ranks 376 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Not well-characterized as population baseline; routinely framed as irreversible in clinical culture despite contrary trial evidence.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 79.0 (trials 29.0, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 1 active / not yet recruiting, 6 completed, 1 other |
| Linked publications | 16 (5 clinical trial publications, 4 Cochrane reviews, 4 systematic reviews, 3 meta-analyses) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT05199129 | Clinical Efficacy and Safety Evaluation of HCP1904-3 in Essential Hypertension Patients 2021 | completed | Phase 3 | 166 |
| NCT00696384 | A Safety and Tolerability Study of Azilsartan Medoxomil in Participants With Essential Hypertension 2007 | completed | Phase 3 | 418 |
| NCT00695955 | One-Year Safety and Tolerability Study of Azilsartan Medoxomil in Participants With Essential Hypertension 2007 | completed | Phase 3 | 669 |
| NCT07116863 | A Multicenter, Randomized, Double-Blind Phase 3 Trial of KDF1901 in Patients With Essential Hypertension 2022 | completed | Phase 3 | 286 |
| NCT03928145 | Efficacy of Chlorthalidone and Hydrochlorothiazide Combined With Amiloride on Blood Pressure in Primary Hypertension. 2019 | status unknown | Phase 3 | 84 |
| NCT06282549 | Study to Evaluate the Efficacy and Safety of TEL/AML/CTD in Elderly Patients with Essential Hypertension 2022 | active, not recruiting | Not applicable | 1,219 |
| NCT01083017 | Resistant Arterial Hypertension Cohort Study 2011 | completed | Not applicable | 74 |
| NCT04470830 | A Study for PMS of AZL-M/CLD FDC in the Treatment of Participants With Essential HTN in South Korea 2019 | completed | Not applicable | 718 |
Published literature
- Clinical trial publication Individual participant-level analysis of four randomized clinical trials examined therapeutic effects of blood pressure lowering on hierarchical kidney outcome using win statisticsLiu Y, Lyu Y, Liu Y et al. · Kidney international · 2026 · PMID 41903707
- Clinical trial publication Low-Dose TEL/AML/CHTD SPC Versus Standard-Dose TEL in Hypertension: Phase III RCTAhn JC, Lee CW, Ahn JH et al. · Hypertension (Dallas, Tex. : 1979) · 2026 · PMID 41717679
- Clinical trial publication Single-Pill Low-Dose Triple Combination Therapy vs Standard-Dose Monotherapy in Patients With Mild-to-Moderate HypertensionSung KC, Park K, Kim DH et al. · Journal of the American College of Cardiology · 2026 · PMID 41670573
- Clinical trial publication Per-Protocol Analysis of Chlorthalidone Versus Hydrochlorothiazide for Cardiovascular Event Prevention-Diuretic Comparison ProjectAnand ST, Hau C, Davenport MJ et al. · Journal of the American Heart Association · 2026 · PMID 41614323
- Clinical trial publication Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical TrialIshani A, Hau C, Raju S et al. · JAMA network open · 2024 · PMID 39656458
- Cochrane review Efficacy and safety of adrenergic alpha-1 receptor antagonists in older adults: a systematic review and meta-analysis supporting the development of recommendations to reduce potentially inappropriate prescribingMansbart F, Kienberger G, Sönnichsen A et al. · BMC geriatrics · 2022 · PMID 36171560
- Meta-analysis New wrinkles in hypertension management 2022Carey RM, Whelton PK · Current opinion in cardiology · 2022 · PMID 35731676
- Meta-analysis Chlorthalidone versus hydrochlorothiazide: major cardiovascular events, blood pressure, left ventricular mass, and adverse effectsRoush GC, Messerli FH · Journal of hypertension · 2021 · PMID 33470735
- Meta-analysis Network meta-analysis of efficacy and safety of chlorthalidone and hydrochlorothiazide in hypertensive patientsDineva S, Uzunova K, Pavlova V et al. · Blood pressure monitoring · 2021 · PMID 32909966
- Systematic review Evaluating the Safety and Tolerability of Azilsartan Medoxomil Alone or in Combination With Chlorthalidone in the Management of Hypertension: A Systematic ReviewKatsi V, Michalakeas C, Soulaidopoulos S et al. · Current hypertension reviews · 2021 · PMID 33438552
- Cochrane review Combining angiotensin receptor blockers with chlorthalidone or hydrochlorothiazide - which is the better alternative? A meta-analysisFilipova E, Dineva S, Uzunova K et al. · Systematic reviews · 2020 · PMID 32838806
- Systematic review Single-pill Combination Therapy of Azilsartan Medoxomil/Chlorthalidone for Treatment of Hypertension: A Systematic ReviewKwon A, Kim GH · Clinical therapeutics · 2020 · PMID 32595000
- Systematic review Hydrochlorothiazide vs chlorthalidone, indapamide, and potassium-sparing/hydrochlorothiazide diuretics for reducing left ventricular hypertrophy: A systematic review and meta-analysisRoush GC, Abdelfattah R, Song S et al. · Journal of clinical hypertension (Greenwich, Conn.) · 2018 · PMID 30251403
- Systematic review Hydrochlorothiazide and alternative diuretics versus renin-angiotensin system inhibitors for the regression of left ventricular hypertrophy: a head-to-head meta-analysisRoush GC, Abdelfattah R, Song S et al. · Journal of hypertension · 2018 · PMID 29465713
- Cochrane review Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertensionMusini VM, Nazer M, Bassett K et al. · The Cochrane database of systematic reviews · 2014 · PMID 24869750
- Cochrane review Meta-analysis of dose-response relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and uratePeterzan MA, Hardy R, Chaturvedi N et al. · Hypertension (Dallas, Tex. : 1979) · 2012 · PMID 22547443
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Chlorthalidone approved for Hypertension?
Chlorthalidone has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Hypertension would be drug repurposing rather than first-in-human development. This does not mean it is approved for Hypertension. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Chlorthalidone in clinical trials for Hypertension?
ClinicalTrials.gov lists 8 registered trials linking Chlorthalidone to Hypertension: 1 is active or not yet recruiting; 6 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT00695955). The largest enrolment is 1219 participants (NCT06282549). Registration activity spans 2007 to 2022.
What does the evidence show for Chlorthalidone in Hypertension?
Chlorthalidone has both completed registered trials and synthesis-level publications linked to Hypertension. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.