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Essential HypertensionPhase 4BETTERNCT05880056

Study of Bisoprolol (Nerkardou - Nerhadou International) 5 and 10 mg Oral Dissolvable Film (ODF) Treatment in Egyptian Patients With Essential Hypertension

A Phase 4 study testing Nerkardou (5 mg) & (10 mg) in people with Essential Hypertension, run by Genuine Research Center, Egypt at 1 site in Egypt.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The trial is designed to assess the safety and investigation of the efficacy of a single oral dose of bisoprolol (Nerkardou - Nerhadou) oral dissolvable film (ODF) 5 \& 10 mg, and patients' compliance in the treatment of essential hypertension. Read more about this study

Who is it for?
Ages 21 to 65 years
Conditions the study is for
Essential Hypertension
What is being tested?
Nerkardou (5 mg) & (10 mg)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
406 participants
Where
1 siteEgypt
Study dates
8 Aug 2024to 1 Apr 2025
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The participant is willing and able to give informed consent for participation in the trial.
  • Male or Female, aged ≥ 21 and < 65 years.
  • The subject with Body mass index (BMI) greater than or equal to 18.5 and below 30 kg/m2
  • Newly diagnosed hypertensive patients with grade 1 and 2 are defined according to the recent ESC/ESH guidelines as follows:
  • Grade 1 hypertension: SBP 140 to 159mmHg and/or DBP 90 to 99mmHg
  • Grade 2 hypertension: SBP 160 to 179mmHg and/or DBP 100 to 109mmHg at screening.
Show all 11Show fewer
  • Non-responders to the 1ST line of therapy for hypertension other than beta blocker and can be safely switched to Bisoprolol (Nerkardou) according to PI decision.
  • Subject doesn't have other comorbidity according to the assessment of the medical history, electrocardiogram (ECG), echocardiogram vital signs, physical examination, and laboratory results.
  • Subject with heart rate (HR) ≥ 80 (BPM) at baseline.
  • Female subjects in childbearing period, and not on a reliable contraceptive method must adhere to the recommended contraceptive methods as detailed in Appendix I.
  • Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.

Who cannot join

  • Grade III hypertension or malignant hypertension (Hypertensive crisis: Systolic over 180 and/or diastolic over 120).
  • Subjects who are not legible to discontinue current antihypertensives such as calcium channel blockers (CCB), ACE- inhibitors, or diuretics for reasons other than hypertension, or responders to current therapy.
  • Subjects with heart rates less than (<)80 beats at rest.
  • Subjects with renal impairment (serum creatinine > 2.0 milligram per deciliter [mg/dL])
  • Subjects with unrecovered pulmonary edema
  • Subjects with a history of cardiovascular surgeries.
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  • Significant history of hypersensitivity to bisoprolol, amlodipine, other dihydropyridines, or any related products (including excipients of the formulations)
  • Presence of diabetes mellitus
  • History or presence of asthma
  • Presence of significant gastrointestinal, liver, kidney disease, surgery, or any other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs or known to potentiate or predispose to undesired effects.
  • Use of any enzyme-modifying drugs, including strong inhibitors of CYP enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and human immunodeficiency virus [HIV] antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, St. John's wort or other herbal medicine known with effect on CYP enzymes) within 28 days before Day 1 of this trial
  • Acute conditions which might alter renal function (e.g., dehydration, severe infection)
  • History of suicidal tendency, history of, or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
  • Positive pregnancy test (only for females of child-bearing potential), or females breastfeeding a child.
  • Consumption of large quantities of methylxanthine-containing beverages (more than 600 mg caffeine/day: 1 cup (250 mL) of coffee contains approximately 100 mg of caffeine, 1 cup of black or green tea contains approximately 30 mg and 1 glass of cola contains approximately 20 mg caffeine)
  • A participant with a life expectancy of fewer than 6 months, or inappropriate for the medication as defined in the Product Information such as acute heart failure or decompensation of heart insufficiency, that requires a therapy with inotropic agents; cardiogenic shock; AV block grade II or III, sick sinus syndrome, sinoatrial heart block; symptomatic bradycardia; symptomatic hypotonia; severe asthma bronchiolus or severe chronic obstructive airways disease; advanced stages of peripheral arterial disease or Raynaud's Syndrome; untreated pheochromocytoma, metabolic acidosis.
  • Participants who have participated in another research trial involving an investigational product in the past 12 weeks.

Trial locations and contacts

1 site in 1 country.

Mohsen Fathallah, MD, Ph.D contact

Telephone: +224514516

mohsen.fathallah@grc-me.com

Sally Khairat, B.Sc.Pharma contact

Telephone: +224514516

sally.khairat@grc-me.com

Egypt1 site, 1 recruiting

  • Al-Fayoum University Hospital

    Al Fayyum, 63611

    Khaled Khashab, Professor, 0105123662

    Abdelrahman Gamal, assistant Lecturer, 01032773645

    Recruiting

Other trials in Egypt

About this study

Official title: A Prospective, Multicenter, Open-label, Single-arm Interventional Study of Bisoprolol (Nerkardou - Nerhadou International) 5 and 10 mg Oral Dissolvable Film (ODF) Treatment in Egyptian Patients With Essential Hypertension

The trial is designed to assess the safety and investigation of the efficacy of a single oral dose of bisoprolol (Nerkardou - Nerhadou) oral dissolvable film (ODF) 5 \& 10 mg, and patients' compliance in the treatment of essential hypertension. This is a Phase IV, open-label, single-arm, prospective trial where subjects will receive:

  1. Bisoprolol (Nerkardou) at an initial dose of 5 (mg) milligrams once daily for 2 weeks.
  2. If the blood pressure would be greater than or equal to 130/80 mmHg after 2 weeks, then the dose will be titrated to 10 mg once daily (non-responders). Dose-Titration will be done at any follow-up visit based on the response.
  3. The total duration of study treatment will be 12 weeks ±2 days, and the total sample size of the study will be 406 participants.
Read the detailed description

The trial is designed to assess the safety and investigation of the efficacy of a single oral dose of bisoprolol (Nerkardou - Nerhadou) oral dissolvable film (ODF) 5 \& 10 mg \& patients' compliance in the treatment of essential hypertension. This is a Phase IV, open-label, single-arm, prospective trial where subjects will receive:

The subject will initially administer once daily 5 mg bisoprolol (Nerkardou) oral dissolvable film (ODF) for 2 weeks. After the assessment of the subject being a responder, study medication will be maintained till week 12. Response will be assessed for each patient every 2 weeks and dose-titration will be done based on the response and PI decision at any visit. Then, for responders, once daily 5 mg bisoprolol (Nerkardou) oral dissolvable film (ODF will be administered for the subsequent 2 weeks. For non-responders once daily 10 mg bisoprolol (Nerkardou) oral dissolvable film (ODF) will be administered for the subsequent 2 weeks. For those who are still not responding to the higher dose will be shifted to other alternatives according to their merit and they will be included to intention to treat.

A responder is defined by BP response, which is represented in the form of a ≥20 mmHg decreases in sitting through SBP and a ≥10 mmHg decreases in sitting through DBP, or a sitting through SBP of <130 mmHg and a sitting through DBP of <80 mmHg.

The total duration of study treatment will be 12 week (±2days). (Flow chart of trail design Appendix III) and the total sample size of the study will be 406 participants.

The trial has a duration of approximately 14 weeks, including:

  1. Screening (assessments to determine eligibility for entry into the trial, occurring within 14 days to day 1 before treatment initiation (week -2) to (week 0).
  2. Treatment duration (5 mg or 10 mg bisoprolol (Nerkardou) based on the response) (duration of 12 weeks); from Day 1 (week 1) to the end of day 84 ±2days (week 12 ±2days)
  3. Premature withdrawal/ Early Discontinuation
Being tested
Nerkardou (5 mg) & (10 mg)
Medical subject headings
Essential Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nerkardou (5 mg) & (10 mg)Drug

    Also called Bisoprolol oral dissolved film ODF (5 mg) & (10 mg)

    Bisoprolol oral dissolved film ODF(5 mg): equivalent to 5 mg of bisoprolol fumarate Bisoprolol oral dissolved film ODF (10 mg): equivalent to 10 mg of bisoprolol fumarate.

Study groups in NCT05880056
Study groupRoleWhat they receive
(Nerkardou 5 mg) & (Nerkardou 10 mg)ExperimentalOne ODF of bisoprolol 5 mg (Nerkardou 5 mg) Dosage form description: Bisoprolol oral dissolved film ODF: equivalent to 5 mg of bisoprolol fumarate. One ODF of bisoprolol 10 mg (Nerkardou 10 mg) Dosage form description: Bisoprolol oral dissolved film ODF: equivalent to 10 mg of bisoprolol fumarate.
Receives: Drug: Nerkardou (5 mg) & (10 mg)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The frequency of the first dose hypotension

    The frequency of occurrence of the first dose hypotension, which is defined as a fall in systolic blood pressure of 20 mm Hg or more, or to a systolic blood pressure of less than 100 mm Hg, with or without associated symptoms.

    Measured: At day 1 (week 1) within 1-4 hours of the first administration of 5& 10 mg doses

Secondary outcomes (5)

  1. Identifying Bradycardia manifestation Assess the safety of Nerkardou ODF.

    Identify the number of patients with bradycardia manifestation, which is defined as heart rate reduction < 60 (bpm) after drug administration

    Measured: At day 14±2 (week 2), day 28±2 (week 4), day 42± 2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)

  2. Assess the safety of Nerkardou ODF.

    Number of reported AEs

    Measured: At day 14±2 (week 2), day 28±2 (week 4), day 42±2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)

  3. Investigate the efficacy of (Nerkardou) in treating patients with hypertension

    Measuring the response rate for a patient's BP response, which is defined as a ≥20mmHg decrease in sitting through SBP and a ≥10mmHg decrease in sitting through DBP， or a sitting through SBP of <130mmHg and a sitting through DBP of <80mmHg

    Measured: At day 14±2 (week 2), day 28±2 (week 4), day 42±2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)

  4. Investigate the overall response of (Nerkardou) in treating patients with hypertension

    The change of systolic blood pressure from baseline will be measured. The change of diastolic blood pressure from baseline will be measured

    Measured: At the end of day 84±2 (week 12)

  5. Measuring Patients' compliance to this dosage form, especially being easy to carry and easy to use

    Doses returned will be counted at each visit.

    Measured: At day 14±2 (week 2), day 28±2 (week 4), day 42±2 (week 6), day 56±2 (week 8), day 70±2 (week 10), and day 84±2 (week 12)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2023
  2. Study start8 Aug 2024
  3. Primary completion1 Apr 2025 (estimated)
  4. Study completion1 Apr 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
The subject will initially administer once daily 5 mg bisoprolol (Nerkardou) oral dissolvable film (ODF) for 2 weeks. After the assessment of the subject being a responder, study medication will be maintained till week 12. Response will be assessed for each patient every 2 weeks and dose-titration will be done based on the response and PI decision at any visit. Then, for responders, once daily 5 mg bisoprolol (Nerkardou) oral dissolvable film (ODF will be administered for the subsequent 2 weeks. For non-responders once daily 10 mg bisoprolol (Nerkardou) oral dissolvable film (ODF) will be administered for the subsequent 2 weeks. Non responders patients on 10 mg will be shifted to other alternatives according to their merit and those patients will be included to intention to treat.
Masking
None (open label)
Enrolment
406 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05880056
Sponsor's protocol ID
GRC/NE-CV/EG/39/IV
Acronym
BETTER
Status last verified
Aug 2024
First submitted
7 May 2023
Last updated
19 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Fuchs FD, Whelton PK. High Blood Pressure and Cardiovascular Disease. Hypertension. 2020 Feb;75(2):285-292. doi: 10.1161/HYPERTENSIONAHA.119.14240. Epub 2019 Dec 23.

    PubMed 31865786

  • NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021 Sep 11;398(10304):957-980. doi: 10.1016/S0140-6736(21)01330-1. Epub 2021 Aug 24.

    PubMed 34450083

  • Channaraya V, Marya RK, Somasundaram M, Mitra D, Tibrewala KD; BRIGHT investigators. Efficacy and tolerability of a beta-1 selective beta blocker, bisoprolol, as a first-line antihypertensive in Indian patients diagnosed with essential hypertension (BRIGHT): an open-label, multicentric observational study. BMJ Open. 2012 May 14;2(3):e000683. doi: 10.1136/bmjopen-2011-000683. Print 2012.

    PubMed 22586283

  • Hostalek-Gottwald U, Gaciong Z. A growing evidence base for the fixed-dose combination of bisoprolol and amlodipine to manage hypertension. Curr Med Res Opin. 2022 Jul;38(7):1047-1053. doi: 10.1080/03007995.2022.2072087. Epub 2022 May 13.

    PubMed 35510372

  • Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ, Cifkova R, Clement D, Coca A, Dominiczak A, Erdine S, Fagard R, Farsang C, Grassi G, Haller H, Heagerty A, Kjeldsen SE, Kiowski W, Mallion JM, Manolis A, Narkiewicz K, Nilsson P, Olsen MH, Rahn KH, Redon J, Rodicio J, Ruilope L, Schmieder RE, Struijker-Boudier HA, Van Zwieten PA, Viigimaa M, Zanchetti A. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. Blood Press. 2009;18(6):308-47. doi: 10.3109/08037050903450468. No abstract available.

    PubMed 20001654

  • Mancia G, Kreutz R, Brunstrom M, Burnier M, Grassi G, Januszewicz A, Muiesan ML, Tsioufis K, Agabiti-Rosei E, Algharably EAE, Azizi M, Benetos A, Borghi C, Hitij JB, Cifkova R, Coca A, Cornelissen V, Cruickshank JK, Cunha PG, Danser AHJ, Pinho RM, Delles C, Dominiczak AF, Dorobantu M, Doumas M, Fernandez-Alfonso MS, Halimi JM, Jarai Z, Jelakovic B, Jordan J, Kuznetsova T, Laurent S, Lovic D, Lurbe E, Mahfoud F, Manolis A, Miglinas M, Narkiewicz K, Niiranen T, Palatini P, Parati G, Pathak A, Persu A, Polonia J, Redon J, Sarafidis P, Schmieder R, Spronck B, Stabouli S, Stergiou G, Taddei S, Thomopoulos C, Tomaszewski M, Van de Borne P, Wanner C, Weber T, Williams B, Zhang ZY, Kjeldsen SE. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023 Dec 1;41(12):1874-2071. doi: 10.1097/HJH.0000000000003480. Epub 2023 Sep 26.

    PubMed 37345492

  • Deedwania P. Hypertension, dyslipidemia, and insulin resistance in patients with diabetes mellitus or the cardiometabolic syndrome: benefits of vasodilating beta-blockers. J Clin Hypertens (Greenwich). 2011 Jan;13(1):52-9. doi: 10.1111/j.1751-7176.2010.00386.x. Epub 2010 Nov 8.

    PubMed 21214722

  • Prichard BN, Cruickshank JM, Graham BR. Beta-adrenergic blocking drugs in the treatment of hypertension. Blood Press. 2001;10(5-6):366-86. doi: 10.1080/080370501753400665.

    PubMed 11822540

  • Dutta A, Lanc R, Begg E, Robson R, Sia L, Dukart G, Desjardins R, Yacobi A. Dose proportionality of bisoprolol enantiomers in humans after oral administration of the racemate. J Clin Pharmacol. 1994 Aug;34(8):829-36. doi: 10.1002/j.1552-4604.1994.tb02047.x.

    PubMed 7962671

  • Minushkina LO. [Bisoprolol: opportunities in the treatment of hypertension]. Kardiologiia. 2012;52(6):80-5. Russian.

    PubMed 22839675

  • Wee Y, Burns K, Bett N. Medical management of chronic stable angina. Aust Prescr. 2015 Aug;38(4):131-6. doi: 10.18773/austprescr.2015.042. Epub 2015 Aug 3.

    PubMed 26648642

  • Johns TE, Lopez LM. Bisoprolol: is this just another beta-blocker for hypertension or angina? Ann Pharmacother. 1995 Apr;29(4):403-14. doi: 10.1177/106002809502900412.

    PubMed 7633020

  • Lancaster SG, Sorkin EM. Bisoprolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension and angina pectoris. Drugs. 1988 Sep;36(3):256-85. doi: 10.2165/00003495-198836030-00002.

    PubMed 2903820

  • Tjandrawinata RR, Setiawati E, Yunaidi DA, Santoso ID, Setiawati A, Susanto LW. Bioequivalence study of two formulations of bisoprolol fumarate film-coated tablets in healthy subjects. Drug Des Devel Ther. 2012;6:311-6. doi: 10.2147/DDDT.S36567. Epub 2012 Oct 30.

    PubMed 23139624

  • Baxter AJ, Spensley A, Hildreth A, Karimova G, O'Connell JE, Gray CS. Beta blockers in older persons with heart failure: tolerability and impact on quality of life. Heart. 2002 Dec;88(6):611-4. doi: 10.1136/heart.88.6.611.

    PubMed 12433890

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Nerkardou (5 mg) & (10 mg) in people with Essential Hypertension, run by Genuine Research Center, Egypt at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 19 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Mohsen Fathallah, MD, Ph.D (Telephone: +224514516, mohsen.fathallah@grc-me.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The frequency of the first dose hypotension (time frame: At day 1 (week 1) within 1-4 hours of the first administration of 5& 10 mg doses). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05880056, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2024.

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