The Precision Hypertension Care Study

NCT02774460 | Completed Phase 4

• 1 other identifier: PHY201501
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

The PHYSIC study aims to investigate the potential for precision medicine in the treatment of high blood pressure. It is a double-blind, randomized, repeated cross-over trial with six treatment periods: four classes of blood pressure-lowering drugs where treatment with two classes are repeated for each patient. The classes of blood pressure-lowering drugs to be tested are a diuretic, a calcium channel blocker, an ACE-inhibitor and an angiotensin receptor blocker.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Between-person variation in blood pressure-lowering effects of blood pressure-lowering drugs, measured as variation in daytime (10 a.m. to 8 p.m.) ambulatory systolic blood pressure.

  This outcome will be analysed based on measurements on the last day of each treatment period (week 7-9).

Secondary Outcomes (3)

• Between-person variation in side effects of blood pressure-lowering drugs, as measured with a modified section of a validated questionnaire about adverse effects of antihypertensive drugs (PERSYVE section 2.1)

  This outcome will be analysed based on data collected on the next to last day of each treatment period (week 7-9).

• The difference in patient treatment preferences between the blood pressure lowering drug classes, as measured with a treatment preference rating questionnaire.

  This outcome will be analysed based on data collected on the next to last day of each treatment period (week 7-9).

• Overall patient treatment preferences measured with a questionnaire on paper.

  This outcome will be measured on the last visit for each patient, i.e. week 56.

Study Arms (7)

Zestril® (Lisinopril)

ACTIVE COMPARATOR

Inhibition of angiotensin converting enzyme (ACE inhibitor). Treatment step up: 1-2 weeks (10 mg tablet) Target dose: 5-7 weeks (20 mg tablet)

Drug: Zestril®

Atacand® (Candesartan)

ACTIVE COMPARATOR

Angiotensin receptor blocker. Treatment step up: 1-2 weeks (8 mg tablet) Target dose: 5-7 weeks (16 mg tablet)

Drug: Atacand®

Norvasc® (Amlodipine)

ACTIVE COMPARATOR

Calcium channel blocker. Treatment step up: 1-2 weeks (5 mg tablet) Target dose: 5-7 weeks (10 mg tablet)

Drug: Norvasc®

Hydrochlorothiazide® (Hydrochlorothiazide)

ACTIVE COMPARATOR

Diuretic agent. Treatment step up: 1-2 weeks (12,5 mg tablet) Target dose: 5-7 weeks (25 mg tablet)

Drug: Hydrochlorthiazide®

Repeated treatment X

ACTIVE COMPARATOR

Each patient receives all four treatments, and in addition repeats two of the treatments, labeled X and Y. The repeated arms will be given with the same duration and dosing as the other arms.

Drug: Treatment X

Repeated treatment Y

ACTIVE COMPARATOR

Each patient receives all four treatments, and in addition repeats two of the treatments, labeled X and Y. The repeated arms will be given with the same duration and dosing as the other arms.

Drug: Treatment Y

Placebo

PLACEBO COMPARATOR

This is an unblinded placebo run-in which we use to generate baseline values. Each patient will initiate their participation with these 2 weeks of placebo treatment, taking 1 capsule daily.

Drug: Placebo

Interventions

Zestril® DRUG

Treatment step up: 1-2 weeks (10 mg tablet) Target dose: 5-7 weeks (20 mg tablet)

Also known as: Lisinopril

Zestril® (Lisinopril)

Atacand® DRUG

Treatment step up: 1-2 weeks (8 mg tablet) Target dose: 5-7 weeks (16 mg tablet)

Also known as: Candesartan

Atacand® (Candesartan)

Norvasc® DRUG

Treatment step up: 1-2 weeks (5 mg tablet) Target dose: 5-7 weeks (10 mg tablet)

Also known as: Amlodipine

Norvasc® (Amlodipine)

Hydrochlorthiazide® DRUG

Treatment step up: 1-2 weeks (12,5 mg tablet) Target dose: 5-7 weeks (25 mg tablet)

Also known as: Hydrochlorthiazide

Hydrochlorothiazide® (Hydrochlorothiazide)

Treatment X DRUG

Each patient receives all four treatments, and in addition repeats two of the treatments, labeled X and Y. The repeated arms will be given with the same duration and dosing as the other arms.

Repeated treatment X

Treatment Y DRUG

Each patient receives all four treatments, and in addition repeats two of the treatments, labeled X and Y. The repeated arms will be given with the same duration and dosing as the other arms.

Repeated treatment Y

Placebo DRUG

This is an unblinded placebo run-in which we use to generate baseline values. Each patient will initiate their participation with these 2 weeks of placebo treatment, taking 1 capsule daily.

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥40 years and ≤75 years
• Previously diagnosed with hypertension with systolic blood pressure between 140 and 159 mm Hg within five years prior to the start of the trial.
• Pharmacologically untreated or using blood pressure-lowering monotherapy at Visit 1. No blood pressure-lowering medication taken during the placebo run-in period.
• Office systolic blood pressure between 140 and 179 mm Hg and diastolic blood pressure at or below 109 mm Hg at Visit 2.
• Patients must give informed consent to participate in the study.

You may not qualify if:

• Medical history, clinical signs or laboratory results indicating secondary hypertension, including primary aldosteronism or renal artery stenosis
• Evidence of serious hematological, respiratory immunological, renal, hepatic, gastrointestinal, endocrinological, metabolic, neurologic, malignant, psychiatric or other diseases as revealed by medical history, physical examination and/or laboratory assessments.
• Active gout
• Previous or present arterial occlusive diseases such as myocardial infarction (MI), stroke or acute arterial insufficiency (unstable angina pectoris or transient ischemic attacks, (TIA)) or heart failure (NYHA class III or IV, or left ventricular systolic dysfunction irrespectively of function class).
• Moderate or severe aortic or mitral insufficiency.
• Renal failure, including hemo-dialysis or kidney transplant/s.
• Atrial fibrillation in need of rate control.
• Symptomatic hypotension, defined as weakness or syncope upon rising to an erect position associated with a decrease in systolic blood pressure.
• Diabetes requiring insulin or oral glucose-lowering drugs.
• Any history of serious abnormal drug reaction to active or inactive compounds in the study drugs, including angioedema.
• Any condition associated with poor compliance including alcoholism or drug dependence.
• Patients who will not comply with the study protocol as judged by the Investigator.
• Women who are pregnant or lactating or not using appropriate contraception for at least 3 months prior to visit 1. Acceptable contraceptive methods are: combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and vasectomised partner.
• Continuous use of concomitant medication that can interfere with study medication, i.e. digitalis glucosides, sotalol, cholestyramine, colestipol, NSAID, lithium, carbamazepine, CYP3A4-inhibitors, CYP3A4-inducers, dantrolene, diuretics, aliskiren, gold, sympathomimetics, tricyclic antidepressants, antipsychotics, anaesthetics and potassium supplements.
• Clinical laboratory assessment outside normal range at visit 1 and judged clinically significant by the Investigator.

Sponsors & Collaborators

• Uppsala University: lead

Study Sites (1)

Uppsala University hospital, Internal medicine research, Oscar II

Uppsala, SE-752 37, Sweden

Location

Related Publications (2)

• Sundstrom J, Lind L, Nowrouzi S, Lytsy P, Marttala K, Ekman I, Ohagen P, Ostlund O. The Precision HYpertenSIon Care (PHYSIC) study: a double-blind, randomized, repeated cross-over study. Ups J Med Sci. 2019 Jan;124(1):51-58. doi: 10.1080/03009734.2018.1498958. Epub 2018 Sep 28.

  PMID: 30265168 BACKGROUND

• Sundstrom J, Lind L, Nowrouzi S, Hagstrom E, Held C, Lytsy P, Neal B, Marttala K, Ostlund O. Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs: A Randomized Clinical Trial. JAMA. 2023 Apr 11;329(14):1160-1169. doi: 10.1001/jama.2023.3322.

  PMID: 37039792 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Lisinopril; candesartan cilexetil; candesartan; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Johan Sundstrom, Professor

  Uppsala University, Department of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: May 17, 2016
• Study Start: February 20, 2017
• Primary Completion: June 11, 2021
• Study Completion: June 11, 2021
• Last Updated: September 1, 2021

Record last verified: 2021-08

Locations

SE (1)