Clinical Trials Register

Summary
EudraCT Number:	2014-003459-76
Sponsor's Protocol Code Number:	09F401
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-10-23
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-003459-76

A.3

Full title of the trial

REducing blood pressure Variability in Essential hypertension with RAmipril vErsus Nifedipine GITS Trial

Riduzione della variabilità della pressione arteriosa nell’ipertensione essenziale con ramipril o nifedipina GITS

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study of the efficacy of two blood pressure lowering drugs, ramipril and nifedipine GITS, in reducing the variability of blood pressure in patients with high blood pressure.

Studio dell'efficacia di due farmaci antiipertensivi, ramipril e nifedipina GITS, nella riduzione della variabilità della pressione arteriosa in pazienti con pressione arteriosa elevata.

A.3.2

Name or abbreviated title of the trial where available

REVERENT

A.4.1

Sponsor's protocol code number

09F401

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Istituto Auxologico Italiano, IRCCS
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bayer Healthcare
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Istituto Auxologico Italiano, IRCCS
B.5.2	Functional name of contact point	Scientific Secretariat
B.5.3	Address:
B.5.3.1	Street Address	via Ariosto 13
B.5.3.2	Town/ city	Milan
B.5.3.3	Post code	20145
B.5.3.4	Country	Italy
B.5.4	Telephone number	3902619112894
B.5.5	Fax number	3902619112901
B.5.6	E-mail	seg.sci@auxologico.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	nifedipine GITS
D.3.4	Pharmaceutical form	Modified-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NIFEDIPINE
D.3.9.1	CAS number	21829-25-4
D.3.9.3	Other descriptive name	NIFEDIPINE GITS
D.3.9.4	EV Substance Code	SUB09253MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	30 to 60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	ramipril
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RAMIPRIL
D.3.9.1	CAS number	87333-19-5
D.3.9.3	Other descriptive name	RAMIPRIL
D.3.9.4	EV Substance Code	SUB10248MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	10 to 20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

essential hypertension

ipertensione arteriosa essenziale

E.1.1.1

Medical condition in easily understood language

elevated arterial pressure

pressione arteriosa elevata

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10015488
E.1.2	Term	Essential hypertension
E.1.2	System Organ Class	10047065 - Vascular disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the effects of nifedipine GITS and ramipril on different estimates of blood pressure variability (over 24 h, at home, between clinic visits) in subjects with elevated blood pressure variability.

Comparare gli effetti di nifedipina GITS e di ramipril su vari indici di variabilità della pressione arteriosa (nelle 24 ore, a domicilio, tra visite ambulatoriali) in soggetti in cui variabilità della pressione arteriosa è elevata.

E.2.2

Secondary objectives of the trial

To assess whether the degree of treatment-induced changes in blood pressure variability, is related to the degree of regression (or progression) of organ damage, after accounting for mean blood pressure reduction by treatment.

Valutare se il grado di modificazioni di variabilità della pressione arteriosa indotte dai trattamenti utilizzati correla con il grado di regressione (o di progressione) del danno d’organo ipertensivo, tenendo conto delle riduzioni in valore medio della pressione arteriosa indotte dal trattamento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male and female subjects
- Age 35-75 years
- clinic systolic (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg
- daytime blood pressure (BP) on ambulatory BP monitoring (ABPM) ≥135 mmHg systolic and/or ≥85 mmHg diastolic
- home SBP standard deviation (SD) >7 mmHg and/or daytime ambulatory SBP SD >12 mmHg
- patients may be included if untreated or, if treated with one antihypertensive drug or two drugs in low doses, after 2 weeks’ washout period
- written informed consent to participate in the study

- Soggetti di entrambi i sessi, età 35-75 anni
- pressione arteriosa convenzionale sistolica ≥140 mmHg e/o diastolica ≥ 90 mmHg
- valore medio di pressione arteriosa ambulatoria nel periodo diurno ≥135 mmHg (sistolica) e/o ≥85 mmHg (diastolica)
- deviazione standard dei valori della PA sistolica domiciliare >7 mmHg e/o della pressione ambulatoria diurna daytime >12 mmHg
- pazienti non trattati con farmaci antiipertensivi o, se in trattamento con un farmaco o con due farmaci a basso dosaggio, dopo il periodo di washout terapeutico di 2 settimane
- consenso informato scritto

E.4

Principal exclusion criteria

- subjects treated with ≥ 2 antihypertensive drugs (except those on two drugs in low doses)
- treated subjects with on-treatment clinic BP ≥160 mmHg systolic and/or 100 mmHg diastolic
- treated antihypertensive subjects in whom withdrawal of treatment is deemed unethical for other reasons
- Contraindications to study treatments as detailed in the relative Summaries of medical Product Characteristics for ramipril or nifedipine GITS (this includes hypersensitivity, pregnancy and lactation)
- Cardiovascular diseases other than hypertension
- Suspected or confirmed secondary hypertension
- Diabetes mellitus
- Other conditions deemed relevant by the investigator
- BMI ≥35 kg/m2
- known severe obstructive sleep apnea
- Premenopausal women not using effective contraceptive methods
- Elevated probability of noncompliance with the study procedures

- soggetti trattati con ≥ 2 farmaci antiipertensivi (eccetto quelli trattati con due farmaci a bassi dosaggi)
- soggetti trattati con pressione convenzionale sistolica ≥160 mmHg e/o diastolica ≥ 100 mmHg
- soggetti trattati in cui la sospensione della terapia non sarebbe etica per altri motivi
- controindicazioni ai farmaci utilizzati nello studio come descritte nei relative Riassunti delle Caratteristiche del Prodotto per ramipril o nifedipina GITS (compresa ipersensibilità, gravidanza ed allattamento)
- altre malattie cardiovascolari
- ipertensione arteriosa secondaria
- Diabete mellito
- Altre condizioni rilevanti secondo l’investigatore
- indice di massa corporea ≥35 kg/m2
- nota syndrome di apnee notturne ostruttive di grado severo
- femmine in età premenopausale non utilizzanti metodi contraccettivi efficaci
- elevata probabilità di nonaderenza alle procedure dello studio

E.5 End points

E.5.1

Primary end point(s)

Variability (standard deviation) of home systolic blood pressure.

Variabilità (deviazione standard) della pressione arteriosa sistolica domiciliare.

E.5.1.1

Timepoint(s) of evaluation of this end point

Final visit of the main study (10 weeks after randomization)

Visita finale della fase principale dello studio (dopo 10 settimane dalla randomizzazione)

E.5.2

Secondary end point(s)

1) Variability (standard deviation) of home diastolic blood pressure.
2) Short term 24h variability of systolic blood pressure at final visit
3) Short term 24h variability of diastolic blood pressure at final visit
4) Visit-to-visit variability of systolic blood pressure assessed over the three last visits
5) Visit-to-visit variability of diastolic blood pressure assessed over the three last visits
6) Mean 24 hour systolic blood pressure at final visit

1) Variabilità (deviazione standard) della pressione arteriosa diastolica domiciliare
2) Variabilità della pressione arteriosa sistolica nelle 24 ore
3) Variabilità della pressione arteriosa diastolica nelle 24 ore
4) Variabilità della pressione convenzionale sistolica tra visite
5) Variabilità della pressione convenzionale sistolica tra visite
6) Valore medio della pressione arteriosa sistolica nelle 24 ore

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary endpoints 1, 2, 3 and 6: Final visit of the main study (10 weeks after randomization)
Secondary endpoints 4 and 5: The last three visits of the main study (6, 8 and 10 weeks after randomization)

Endpoint secondari 1, 2, 3 e 6: Visita finale della fase principale dello studio (dopo 10 settimane dalla randomizzazione)
Endpoint secondari 4 e 5: Le ultime tre visite dello studio principale (dopo 6, 8 e 10 settimane dalla randomizzazione)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

disegno PROBE

PROBE desing

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

China

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

112

F.4.2.2

In the whole clinical trial

168

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The participants will either continue with the treatment used at study end or, in case of previously treated subjects, revert to previous treatment. At the final visit they will receive advice regarding the subsequent follow-up and additional evaluations, if necessary.

I partecipanti potranno proseguire con la terapia utilizzata al termine dello studio oppure, in caso di soggetti trattati in precedenza, riprendere la terapia precedente. Alla visita finale verranno forniti consigli riguardo a ulteriore follow-up ed eventuali controlli da eseguire.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-02-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-10-23

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials