Management of Newly Diagnosed and Uncontrolled Hypertension With Fixed-Dose Combination of Perindopril/Amlodipine and Perindopril/Indapamide/Amlodipine

NCT03738761 | Completed Phase 4

• 2 other identifiers: KCT 06/20172017-001596-23
• Study Type: interventional
• Target: 471
• Locations: 7 countries
• Sites: 34

Brief Summary

PRECIOUS Study aims to evaluate the efficacy and safety of therapy with fixed-dose combination (FDC) of perindopril/amlodipine (Amlessa®) and FDC of perindopril/indapamide/amlodipine (Co-Amlessa®) on blood pressure reduction in both previously untreated patients and patients with previous antihypertensive therapy. Adult patients with AH who are treatment-naïve with systolic blood pressure (SBP) from 150 mmHg or higher AND/OR diastolic blood pressure (DBP) from 95 mmHg or higher (SBP ≥ 150 mm AND/OR DBP ≥ 90 mmHg for patients with type 2 diabetes mellitus ) and uncontrolled patients on mono, dual or triple antihypertensive therapy with systolic blood pressure (SBP) from 140 mmHg or higher AND/OR diastolic blood pressure (DBP) from 90 mmHg or higher (SBP ≥ 140 AND/OR DBP ≥ 85 mmHg for patients with type 2 diabetes mellitus) will be invited to participate in this study. During 16-week trial, seven study visits are planned. At first study visit physical examination, medical history, BP measurement, electrocardiogram (ECG), laboratory analysis and of Ambulatory Blood Pressure Measurement (ABPM) will be performed. Based on their previous antihypertensive therapy, patients will receive to treatment with either Amlessa® or Co-Amlessa® for the duration of 16 weeks and blood pressure measurements, laboratory investigations and patient interviews will be performed at study follow-up visits to assess the treatment efficacy (proportion of patients reaching normal office blood pressure after 16 weeks of treatment) and safety.

Conditions

Hypertension

Keywords

Hypertension; Blood pressure control; Fixed-dose combination antihypertensives; Ambulatory blood pressure monitoring

Outcome Measures

Primary Outcomes (1)

• Systolic and diastolic blood pressure at Week 16

  Responder rate at end of study (week 16): proportion of patients reaching office normal blood pressure defined as SBP \< 140 mmHg and DBP \< 90 mmHg (patients with type 2 diabetes mellitus: SBP \< 140 mmHg and DBP \< 85 mmHg). BP is measured using a validated automated BP-measuring device.

  16 weeks

Secondary Outcomes (12)

• Systolic and diastolic blood pressure at Week 4, Week 8 and Week 12

  12 Weeks

• Mean absolute and relative change in Systolic and diastolic blood pressure from baseline to Week 4, Week 8, Week 12 and Week 16

  16 weeks

• Average 24-hour blood pressure at Week 16

  16 weeks

• Average awake time blood pressure at Week 16

  16 weeks

• Average sleep time blood pressure at Week 16

  16 weeks

Other Outcomes (10)

• Change in serum total cholesterol from baseline to end of study (Week 16)

  16 weeks

• Change in HDL-C from baseline to end of study (week 16)

  16 weeks

• Change in LDL-C from baseline to end of study (week 16)

  16 weeks

Study Arms (2)

Amlessa® Arm

EXPERIMENTAL

Patients allocated to treatment with Amlessa® (starting FDC of perindopril 4mg/amlodipine 5mg) according to their previous antihypertensive therapy and as described in the protocol inclusion criteria.

Drug: Amlessa®; Drug: Co-Amlessa®

Co-Amlessa® Arm

EXPERIMENTAL

Patients allocated to treatment with Co-Amlessa® (starting FDC perindopril 4mg/indapamide 2,5mg/amlodipine 5mg) according to their previous antihypertensive therapy and as described in the protocol inclusion criteria. Patients on previous perindopril and amlodipine therapy will be automatically assigned to Co-Amlessa® arm.

Drug: Co-Amlessa®

Interventions

Amlessa® DRUG

Fixed-dose combination (FDC) of perindopril/amlodipine, tablets. Strengths: 4mg/5 mg, 8mg/5 mg, 8mg/10 mg.

Amlessa® Arm

Co-Amlessa® DRUG

Fixed-dose combination (FDC) of perindopril/indapamide/amlodipine, tablets. Strengths: 4mg/1.25 mg/5 mg, 8mg/2.5 mg/5 mg, 8mg/2.5 mg/10 mg.

Amlessa® Arm; Co-Amlessa® Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with essential arterial hypertension.\*
• Men and women aged ≥ 18 years
• Written informed consent
• Ability to adhere to study protocol
• Patients with essential arterial hypertension:
• Naïve patients with systolic blood pressure (SBP) from 150 mmHg or higher AND/OR diastolic blood pressure (DBP) from 95 mmHg or higher (SBP ≥ 150 AND/OR DBP ≥ 90 mmHg for patients with type 2 diabetes mellitus)
• Uncontrolled patients on antihypertensive monotherapy with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP ≥ 140 AND/OR DBP ≥ 85 mmHg for patients with type 2 diabetes mellitus).
• Uncontrolled patients on dual antihypertensive therapy (either in monoforms or FDC) with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP ≥ 140 AND/OR DBP ≥ 85 mmHg for patients with type 2 diabetes mellitus).
• Patients with essential arterial hypertension (AH):
• Uncontrolled patients on dual antihypertensive therapy (either in monoforms or FDC, including perindopril+amlodipine combination) with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP ≥ 140 AND/OR DBP ≥ 85 mmHg for patients with type 2 diabetes mellitus).
• Uncontrolled patients on triple antihypertensive therapy (either in monoforms or FDC) with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP ≥ 140 AND/OR DBP ≥ 85 mmHg for patients with type 2 diabetes mellitus).

You may not qualify if:

• History of adverse reactions or hypersensitivity associated with the use of the active substances, or any other components of the Investigational medicinal products (IMPs) used in the trial.
• Hereditary/idiopathic angioedema.
• Known secondary AH (e.g. pheochromocytoma, primary aldosteronism, renal artery stenosis).
• Office measured Systolic blood pressure ≥200 mmHg.
• Unstable angina pectoris.
• Acute heart failure and heart failure New York Heart Association (NYHA) Class IV.
• Antihypertensive drugs used for other indication than AH (e.g. tachyarrhythmia, glaucoma) less than 3 months before the study or in changed dosages less than 3 months before the study.
• Severe liver impairment OR biliary cirrhosis OR cholestasis OR hepatic encephalopathy.
• Renal dysfunction - glomerular filtration rate (GFR) \<60 ml/min, bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients with only 1 kidney, or post-renal transplant patients, dialysis patients.
• Any of the following clinically relevant laboratory or ECG findings:
• significant anaemia with haemoglobin less than 100 g/l
• serum aspartate transaminase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase (ALP) and/or gamma-glutamyltransferase (GGT) of more than 3 x upper limit of normal (ULN)
• hyperkalaemia (serum potassium of more than 5 mmol/l)
• A-V block grade 2 or 3
• ECG signs of acute ischemia

Sponsors & Collaborators

• KRKA: lead
• Clinres Farmacija d.o.o.: collaborator
• University Medical Centre Ljubljana: collaborator

Study Sites (34)

Unimed medical center

Abovyan, Armenia

Location

Center of Preventive Cardiology

Yerevan, Armenia

Location

Thalassotherapia Opatija, Specijalna bolnica za medicinsku rehabilitaciju, bolesti srca, pluća i reumatizma, Klinika za liječenje, rehabilitaciju i prevenciju bolesti srca i krvnih žila

Opatija, Croatia

Location

KBC Rijeka - Sušak, Klinika za internu medicinu, Zavod za nefrologiju, dijalizu i transplantaciju bubrega

Rijeka, Croatia

Location

KB Merkur, Klinika za unutarnje bolesti, Zavod za kardiologiju

Zagreb, Croatia

Location

KBC Sestre milosrdnice, Klinika za bolesti srca i krvnih žila, Zavod za bolesti krvnih žila

Zagreb, Croatia

Location

KBC Zagreb, Klinika za bolesti srca i krvnih žila

Zagreb, Croatia

Location

KBC Zagreb, Klinika za unutarnje bolesti, Zavod za nefrologiju, arterijsku hipertenziju, dijalizu i transplantaciju

Zagreb, Croatia

Location

Poliklinika za prevenciju kardiovaskularnih bolesti i rehabilitaciju SRČANA

Zagreb, Croatia

Location

Biatros Kft.

Biatorbágy, Hungary

Location

General practitioner office

Budapest, Hungary

Location

AD SANITATEM Bt.

Pilisvörösvár, Hungary

Location

Przychodnia Kardiologiczna w Zespole Przychodni Specjalistycznych DIAB-END-COR

Krakow, Poland

Location

Niepubliczny Zakład Opieki Zdrowotnej Neuromed M.i M. Nastaj Spółka Partnerska

Lublin, Poland

Location

Poradnia Kardiologiczna, Nowodworskie Centrum Medyczne

Nowy Dwór Mazowiecki, Poland

Location

Poradnia Kardiologiczna Samodzielnego Publicznego Zespołu Zakładów Opieki Zdrowotnej im. Marszałka Józefa Piłsudskiego w Płońsku

Płońsk, Poland

Location

Poradnia Kardiologiczna w Niepublicznym Zakładzie Opieki Zdrowotnej Euro-Klinika Sp. z o.o. w Siemianowicach Śląskich

Siemianowice Śląskie, Poland

Location

Poradnia internistyczno-kardiologiczna w Niepublicznym Zakładzie Opieki Zdrowotnej AURUM

Warsaw, Poland

Location

Poradnia Kardiologiczna w Przychodni Rejonowej - Specjalistycznej (III) Samodzielnego Zespołu Publicznych Zakładów Lecznictwa Otwartego Warszawa - Ochota

Warsaw, Poland

Location

Przychodnia ACTIV-MED.

Warsaw, Poland

Location

Federal State Budgetary Scientific Institution "Scientific Research Institute of Complex Problems of Cardiovascular Diseases"

Kemerovo, Russia

Location

Federal State budget organization National medical research center of cardiology of the Ministry of healthcare of the Russian Federation

Moscow, Russia

Location

State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital № 29 named after N.E. Bauman of Department of Healthcare of Moscow city" (SBIH "CCH № 29 Bauman")

Moscow, Russia

Location

Federal State Budgetary Institution "V.A. Almazov National Medical Research Center" of the Ministry of Health of the Russian Federation (V.A. Almazov NMRC)

Saint Petersburg, Russia

Location

Federal State Budgetary Educational Institution Higher Education "Volgograd State Medical University" of the Ministry of Healthcare of the Russian Federation (FSBEI HE VolgSMU MOH Russia)

Volgograd, Russia

Location

KBC Dragiša Mišović

Belgrade, Serbia

Location

Klinički centar Srbije

Belgrade, Serbia

Location

Inštitut za kardiovaskularne bolesti Vojvodine

Kamenitz, Serbia

Location

Klinički centar Niš

Niš, Serbia

Location

Univerzitetna klinika za pljučne bolezni in alergijo Golnik

Golnik, Slovenia

Location

Splošna bolnišnica Jesenice

Jesenice, Slovenia

Location

Ordinacija interne medicine Verboten Kopriva Renata

Litija, Slovenia

Location

MC Medicor, d. d.

Ljubljana, Slovenia

Location

Intermed, d. o. o.

Maribor, Slovenia

Location

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• Jassim Al Khaja KA, Sequeira RP, Mathur VS. Rational pharmacotherapy of hypertension in the elderly: analysis of the choice and dosage of drugs. J Clin Pharm Ther. 2001 Feb;26(1):33-42. doi: 10.1046/j.1365-2710.2001.00324.x.

  PMID: 11286605 BACKGROUND

• Gosse P. Perindopril/indapamide combination in the first-line treatment of hypertension and end-organ protection. Expert Rev Cardiovasc Ther. 2006 May;4(3):319-33. doi: 10.1586/14779072.4.3.319.

  PMID: 16716093 BACKGROUND

• Brguljan Hitij J, Gaciong Z, Simic D, Vajer P, Zelveian P, Chazova IE, Jelakovic B; Precious trial investigators. Differences in sex and age response to single pill combination based antihypertensive therapy reflecting in blood pressure and arterial stiffness. J Hypertens. 2025 Mar 1;43(3):387-396. doi: 10.1097/HJH.0000000000003901. Epub 2024 Nov 7.

  PMID: 39445609 DERIVED

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Jana Brguljan Hitij

  University Medical Centre Ljubljana Hospital dr. Peter Držaj

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Treatment is started at Visit 1 with Amlessa® 4mg/5mg (Amlessa® Arm) or Co-Amlessa® 4mg/1,25mg/5mg (Co-Amlessa® Arm) for 4 weeks. At each of the three follow-up visits (at week 4, week 8 and week 12) patient BP is assessed and if normal office blood pressure was achieved, the treatment with the study medication prescribed for the previous treatment period is continued. If normal office blood pressure was not achieved at any of the follow-up visits (week 4, week 8 and week 12), Amlessa® or Co-Amlessa® strength is increased in accordance with the below sequence. Amlessa® Arm Amlessa® 4mg/5mg (initial therapy) - Amlessa® 8mg/5mg - Amlessa® 8mg/10mg - Co-Amlessa® 8mg/2,5mg/10mg Co-Amlessa® Arm Co-Amlessa® 4mg/1,25mg/5mg - Co-Amlessa® 8mg/2,5mg/5mg - Co-Amlessa® 8mg/2,5mg/10mg - end of study no further escalation of study medication dosage Normal office BP is defined as SBP \< 140 mmHg and DBP \< 90 mmHg; patients with type 2 diabetes mellitus: SBP \< 140 mmHg and DBP \< 85 mmHg.

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: November 13, 2018
• Study Start: February 13, 2018
• Primary Completion: September 27, 2019
• Study Completion: September 27, 2019
• Last Updated: September 2, 2020

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

HU (3); AR (2); RU (5); SE (4); SL (5); CR (7); PL (8)