Clinical Trials Register

Summary
EudraCT Number:	2014-000269-27
Sponsor's Protocol Code Number:	DSCK101
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-06-23
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

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2014-000269-27

A.3

Full title of the trial

Efficacy and tolerance of Beta Blocker and Procoralan uptitration in chronic heart failure patients under telemedical control: „70 bpm on day 28“

Wirksamkeit und Verträglichkeit einer kombinierten Betablocker und Procoralan-Therapie bei Patienten mit chronischer Herzinsuffizienz unter telemedizinischer Kontrolle: "70 /min am Tag 28"

A.3.1

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

Will it be better to use Beta Blocker and Procoralan when suffering of chronical heart failure, in order to reduce heart frequence at rest?

Ist es bei chronischer Herzschwäche besser und verträglicher Betablocker und Procoralan zu kombinieren, um Ihre Herzfrequenz ausreichend zu senken?

A.3.2

Name or abbreviated title of the trial where available

EARLY

A.4.1

Sponsor's protocol code number

DSCK101

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	German Foundation for Chronically Ill
B.1.3.4	Country	Germany
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	German Foundation for Chronically Ill
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Servier Deutschland GmbH
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	German Foundation for Chronically Ill
B.5.2	Functional name of contact point	Clinical Trial Coordinator
B.5.3	Address:
B.5.3.1	Street Address	Pariser Platz
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	10117
B.5.3.4	Country	Germany
B.5.4	Telephone number	00493030109030
B.5.5	Fax number	00493030102500
B.5.6	E-mail	info@dsck.de

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.2.1.1.1	Trade name	Procoralan
D.2.1.1.2	Name of the Marketing Authorisation holder	Les Laboratoires Servier
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Procoralan
D.3.4	Pharmaceutical form	Film-coated tablet and gastro-resistant granules in sachet
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	IVABRADINE
D.3.9.1	CAS number	155974-00-8
D.3.9.4	EV Substance Code	SUB08357MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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

Patients with chronic heart failure and resting heart rate of ≥ 75 bmp

Patienten mit einer chronischen Herzinsuffizienz und einer Ruhe-Herzfrequenz ≥ 75 /min

E.1.1.1

Medical condition in easily understood language

Patients with chronic heart failure and heart rate at rest of ≥ 75 bits per minutes

Patienten mit einer chronischen Herzinschwäche und einer Herzfrequenz in Ruhe von ≥ 75 Schlägen pro Minute

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Within one month (28 days ± 7 days), patients with CHF under telemedical control and a resting heart rate of ≥ 75 bpm will achieve a resting heart rate of ≤ 70 bpm more often if they are treated with a combination of Ivabradine and beat-blocker compared to a therapy with beta-blocker alone.

Innerhalb eines Monats (28 Tage ± 7 Tage) wird bei Patienten mit chronischer Herzinsuffizienz und einer Ruhe-Herzfrequenz (HF) ≥ 75 /min unter Telemonitoring durch die kombinierte Einnahme von Ivabradin (Procoralan ©) mit Betablockern eine Ruhe-Herzfrequenz von HF ≤ 70 /min häufiger erreicht als bei einer alleinigen Therapie mit Betablockern (BB).

E.2.2

Secondary objectives of the trial

After one month (T1):
•How many patients reach a heart rate ≤ 70 bpm?
•What is the mean difference in heart rate compared to a heart rate of 70 bpm?
•What is the mean reduction of hear rate?
•What is the change in quality of life?
•What is the change in NYHA classification?
•What is the change of the 6-minute walk test?
•Does the compliance differ between the groups?
After 4 month:
•How differs the progress in therapy and the therapy success between an early and a late entry of Ivabradin into the therapy?

nach einem Monat (T1):
•Wie viele Patienten erreichen eine Herzfrequenz ≤ 70 /min?
•Wie groß ist der mittlere Unterschied der von den Patienten erreichten Herzfrequenz im Vergleich zu einer Herzfrequenz = 70 /min?
•Um wie viel wurde die Herzfrequenz der Patienten im Mittel gesenkt?
•Wie verändert sich die Lebensqualität? Gemessen mit EQ-5D (vom Patienten selbst in T0 (Einschlussuntersuchung) und T1 auszufüllen) und KCCQ (von vitaphone in nach T0 und T1 zu erheben)?
•Wie verändert sich die NYHA-Klassifizierung?
•Wie verändert sich der 6-Minuten-Gehtest?
•Wie ist die Therapietreue unter BB + Ivabradin (Procoralan ©) gegenüber der bei einer Therapie nur mit BB?
nach 4 Monaten (T2)
•Wie unterscheiden sich die Therapieverläufe und Therapieergebnisse zwischen einem frühzeitigen und einem späteren Beginn der Ivabradin (Procoralan ©) – Therapie?

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Symptomatic heart failure with reduced left ventricular function caused by dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICMP)
•Heart rate ≥ 75 bpm
•NYHA Class II-IV
•Sinus rhythm
•Cognitive capacity
•Age ≥ 18 years
•Stable HF medication including beta-blocker
•Dose of beta-blocker ≤ 50% of advised dose according to German product information or beta-blocker naive patient
•Signed informed consent

•Symptomatische Herzinsuffizienz mit reduzierter Pumpfunktion aufgrund einer Dilatativen Kardiomyopathie (DCMP) oder Ischämischen Kardiomyopathie (ICMP)
•Herzfrequenz ≥ 75 /min
•NYHA Klasse II-IV
•Sinusrhythmus
•Kognitive Aufnahmefähigkeit
•Alter ≥ 18Jahre
•Stabile HI-Medikation, einschließlich BB
•BB-Dosis bei Einschluss ≤ 50% der BB-Zieldosis nach deutscher Fachinformation (siehe 5.3) oder BB-naiver Patient
•Bereitschaft zur Teilnahme, dokumentiert durch informed consent

E.4

Principal exclusion criteria

•Pregnancy
•Systolic blood pressure < 95 mm Hg
Cardiac decompensation within the last 8 weeks prior to recruitment
•Significantly reduced renal function (GFR < 30)
•Planned invasive medical intervention within the next 8 weeks
•Lack of communication skills
•Permanent atrial fibrillation and/or paroxysmal AF documented in two ECGs
•Implanted active CRT-Device or active pacemaker
•Patients with a contraindication for beta-blocker therapy
•Patients under current Ivabradine-therapy
•Patients paticipats in a competing clinical trial (identical/overlapping) inclusion criteria
•Patients living in a geographic region without sufficient cell network coverage

•Schwangerschaft
•Systolischer Blutdruck < 95 mm Hg
•Kardiale Dekompensation innerhalb der letzten 8 Wochen vor Einschluss
•Signifikante Schädigung der Niere (GFR < 30)
•Geplante Intervention innerhalb der nächsten 8 Wochen
•Mangelnde Kommunikationsfähigkeit
•permanentes Vorhofflimmern und/oder paroxysmales VHF in 2 EKG-Dokumentationen
•implantiertes CRT-Device oder aktive Frequenzadaption im Schrittmacher-Device
•Patient mit BB Kontraindikation
•Patienten unter Ivabradin (Procoralan ©) –Therapie
•Patient nimmt an einer konkurrierenden klinischen Prüfung teil (deckungsgleiche/überlappende Auswahlkriterien)
•Patient wohnt in einem Gebiet ohne ausreichende Netzabdeckung

E.5 End points

E.5.1

Primary end point(s)

Resting heart rate ≤ 70 bpm at T1

Ruhefrequenz ≤ 70/min bei T1

E.5.1.1

Timepoint(s) of evaluation of this end point

28 (+/-7) days after individual start of the study

28 (+/-7) Tage nach individuellem Studienstart

E.5.2

Secondary end point(s)

•Difference between heart rate and target level of 70 bpm at T1
•Mean reduction in heart rate between T0 and T1
•Changes in KCCQ from T0 to T1
•Changes in EQ-5D from T0 to T1
•Changes in NYHA classification from T0 to T1
•Changes in 6 minute walk test from T0 to T1
•Therapy compliance in T1
•Drop outs

•Differenz der Herzfrequenz zum Zielwert von 70 /min bei T1
•Mittlere Senkung der Herzfrequenz von T0 bis T1
•Veränderung KCCQ von T0 nach T1
•Veränderung EQ-5D von T0 nach T1
•Veränderung NYHA von T0 nach T1
•Veränderung 6-Minuten-Gehtest von T0 nach T1
•Therapietreue bei T1
•Therapieabbruch bis T1

E.5.2.1

Timepoint(s) of evaluation of this end point

28 (+/-7) days after individual start of the study

28 (+/-7) Tage nach individuellem Studienstart

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

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Standardtherapie einschließlich Betablocker

standard of care including beta blockers

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

The trial ends after the last patient (calculation of power and sample size: 120 patients) finishes the time within the study (according to study protocoll after 4 month).

Die Studie endet regulär, wenn der letzte Patient (laut Fallzahlenberechnung 120 Patienten) die Studie laut Studienprotokoll, also nach 4 Monaten abschließt."

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

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:

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2014-06-23.

Yes

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

120

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)

Three month after the first endpoint patients are under telemedical control. Study ends with a final examination of the patient after 4 month. Patients are treated according to guidlines. Infomation are given to the gerneral practitioner and the cardiologist that will continue the therapy. There will be no difference from the expexted normal treatment of patients with CHF. Patients can continue on trial medication on a prescription basis.

In den drei Monaten nach dem ersten Endpunkt werden die Patienten telemedizinisch überwacht. Die Studie endet für den Patienten nach insgesamt 4 Monaten. Die Behandlung erfolgt nach den Leitlinien für HI. Der behandelnde Hausarzt und der Kardiologe erhalten Informationen zu der Studie. Es werden keine Änderungen zu der normalen Therapie bei Patienten mit chronischer Herzinsuffizienz erwartet. Patienten können die Studienmedikation auf Rezeptbasis weiterführen.

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

2014-11-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-08-12

P. End of Trial
P.	End of Trial Status	Ongoing

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