amlodipine/indapamide/telmisartan (GMRx2) / George Medicines - LARVOL DELTA

Single-pill combination therapy is the standard of care for hypertension, but it is time for the next step: Implementation. (PubMed, Med) - "The GMRx2 trial1 in adults with high blood pressure (BP) demonstrated that after 12 weeks, a low-dose single-pill combination of telmisartan, amlodipine, and indapamide significantly reduced BP levels compared to several dual combinations (telmisartan with amlodipine, telmisartan with indapamide, or amlodipine with indapamide). Adverse events did not differ between the groups. This novel therapeutic option could improve high BP control."

Combination therapy • Journal • Cardiovascular • Hypertension

Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial. (PubMed, Lancet) - P3 | "A novel low-dose SPC product of telmisartan, amlodipine, and indapamide provided clinically meaningful improvements in blood pressure reduction compared with dual combinations and was well tolerated. This SPC provides a new therapeutic option for the management of hypertension and its use could result in a substantial improvement in blood pressure control in clinical practice."

Clinical • Journal • Cardiovascular • Hypertension

Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination Compared With Placebo for Initial Treatment of Hypertension. (PubMed, J Am Coll Cardiol) - P3 | "In a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo. (Efficacy and Safety of GRMx2 Compared to Placebo for the Treatment of Hypertension: NCT04518306)."

Clinical • Journal • Cardiovascular • Hypertension

Low-Dose Triple-Pill vs Standard-Care Protocols for Hypertension Treatment in Nigeria: A Randomized Clinical Trial. (PubMed, JAMA) - "The triple-pill protocol involved a novel combination of telmisartan, amlodipine, and indapamide in triple one-quarter, one-half, and standard doses (ie, 10/1.25/0.625 mg, 20/2.5/1.25 mg, and 40/5/2.5 mg), with accelerated up-titration...Among Black African adults with uncontrolled hypertension, a low-dose triple-pill protocol achieved better blood pressure lowering and control with good tolerability compared with the standard-care protocol. Pan African Clinical Trials Registry Identifier: PACTR202107579572114."

Clinical • Journal • Cardiovascular • Hypertension

Ask the Trialist - GMRx2 (ESC 2024) - No abstract available

Cardiovascular

Panel discussion - GMRx2, QUADRO and VERONICA-Nigeria (ESC 2024) - No abstract available

Cardiovascular

Discussant review - GMRx2, QUADRO and VERONICA-Nigeria (ESC 2024) - No abstract available

Review • Cardiovascular

GMRx2 - Efficacy and safety of a novel triple single pill combination (ESC 2024) - No abstract available

Clinical • Cardiovascular

Rationale for a New Low-Dose Triple Single Pill Combination for the Treatment of Hypertension. (PubMed, Glob Heart) - "Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up."

Journal • Cardiovascular • Hypertension

GMRx2_PCT: Efficacy and Safety of GMRx2 Compared to Placebo for the Treatment of Hypertension (clinicaltrials.gov) - P3 | N=295 | Completed | Sponsor: George Medicines PTY Limited | Recruiting ➔ Completed | Trial completion date: May 2023 ➔ Oct 2023 | Trial primary completion date: Mar 2023 ➔ Sep 2023

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension

GMRx2_ACT: Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension (clinicaltrials.gov) - P3 | N=1385 | Completed | Sponsor: George Medicines PTY Limited | Recruiting ➔ Completed | Trial primary completion date: Mar 2023 ➔ Aug 2023

Trial completion • Trial primary completion date • Cardiovascular • Hypertension

TRIPLE THERAPY PREVENTION OF RECURRENT INTRACEREBRAL DISEASE EVENTS TRIAL (TRIDENT): PROGRESS REPORT (ESOC 2023) - P3 | "TRIDENT aims to determine the effects of a novel SPC ‘Triple Pill’, three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20mg, amlodipine 2.5mg, indapamide 1.25mg), with placebo, for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH... Low-dose Triple Pill BP lowering could improve long-term outcome from ICH."

Cardiovascular • Hypertension • Myocardial Infarction

GMRx2_PCT: Efficacy and Safety of GMRx2 Compared to Placebo for the Treatment of Hypertension (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: George Medicines PTY Limited | Trial completion date: Dec 2022 ➔ May 2023 | Trial primary completion date: Sep 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Cardiovascular • Hypertension

GMRx2_ACT: Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension (clinicaltrials.gov) - P3 | N=1500 | Recruiting | Sponsor: George Medicines PTY Limited | Trial completion date: Jul 2022 ➔ Jul 2023 | Trial primary completion date: Mar 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Cardiovascular • Hypertension

TRIPLE THERAPY PREVENTION OF RECURRENT INTRACEREBRAL DISEASE EVENTS TRIAL (TRIDENT): PROGRESS REPORT (ESOC 2022) - P3 | "TRIDENT aims to determine the effects of a novel SPC 'Triple Pill', three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20mg, amlodipine 2.5mg, indapamide 1.25mg), with placebo, for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH. An international, double-blind, placebo-controlled, randomised trial in adults with ICH and mild-moderate hypertension (systolic BP 130-160mmHg), who are not taking any Triple Pill component drug or equivalent at greater than half-dose... Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.Trial registration: ClinicalTrials.gov (NCT02699645)"

Cardiovascular • Hypertension • Myocardial Infarction

GMRx2_PCT: Efficacy and Safety of GMRx2 Compared to Placebo for the Treatment of Hypertension (clinicaltrials.gov) - P3; N=250; Recruiting; Sponsor: George Medicines PTY Limited; Trial completion date: Mar 2022 ➔ Dec 2022; Trial primary completion date: Dec 2021 ➔ Sep 2022

Clinical • Trial completion date • Trial primary completion date • Hypertension

Difficulties in the diagnostics of chronic hyponatremia based on the case study of a 66-year old female patient during antihypertensive therapy. (PubMed, Pol Merkur Lekarski) - "This case report described the atypical presentation of TIH resembling SIADH. TIH diagnosis should be primarily based on the improvement of hyponatremia after the termination of thiazide or thiazide-like diuretic treatment."

Clinical • Journal • Cardiovascular • Fatigue • Heart Failure • Pain

GMRx2_ACT: Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension (clinicaltrials.gov) - P3; N=1500; Recruiting; Sponsor: George Medicines PTY Limited; Not yet recruiting ➔ Recruiting

Enrollment open • Hypertension

GMRx2_PCT: Efficacy and Safety of GMRx2 Compared to Placebo for the Treatment of Hypertension (clinicaltrials.gov) - P3; N=250; Recruiting; Sponsor: George Medicines PTY Limited; Not yet recruiting ➔ Recruiting

Enrollment open • Hypertension

TRIDENT MRI: Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial Magnetic Resonance Imaging Sub-study (clinicaltrials.gov) - P=N/A; N=4; Terminated; Sponsor: The George Institute; N=750 ➔ 4; Trial completion date: Dec 2023 ➔ Mar 2021; Recruiting ➔ Terminated; Trial primary completion date: Dec 2023 ➔ Mar 2021; Not feasible to continue

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Dementia • Hematological Disorders • Hypertension

GMRx2_ACT: Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension (clinicaltrials.gov) - P3; N=1500; Not yet recruiting; Sponsor: George Medicines PTY Limited; Initiation date: Jan 2021 ➔ Jun 2021; Trial primary completion date: Aug 2021 ➔ Dec 2021

Clinical • Trial initiation date • Trial primary completion date • Hypertension

GMRx2_PCT: Efficacy and Safety of GMRx2 Compared to Placebo for the Treatment of Hypertension (clinicaltrials.gov) - P3; N=250; Not yet recruiting; Sponsor: George Medicines PTY Limited; Trial completion date: Nov 2021 ➔ Mar 2022; Initiation date: Jan 2021 ➔ May 2021; Trial primary completion date: Aug 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Hypertension

TRIDENT COG: Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study (clinicaltrials.gov) - P3; N=1; Terminated; Sponsor: The George Institute; N=403 ➔ 1; Trial completion date: Dec 2023 ➔ Feb 2021; Recruiting ➔ Terminated; Trial primary completion date: Dec 2023 ➔ Feb 2021; Contractual and financial issues.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Dementia • Hematological Disorders • Hypertension

GMRx2_PCT: Efficacy and Safety of GMRx2 Compared to Placebo for the Treatment of Hypertension (clinicaltrials.gov) - P3; N=250; Not yet recruiting; Sponsor: George Medicines PTY Limited

Clinical • New P3 trial • Hypertension

GMRx2_ACT: Efficacy and Safety of GMRx2 Compared to Dual Combinations for the Treatment of Hypertension (clinicaltrials.gov) - P3; N=1500; Not yet recruiting; Sponsor: George Medicines PTY Limited

Clinical • New P3 trial • Hypertension