Condition category
Urological and Genital Diseases
Date applied
09/04/2018
Date assigned
17/04/2018
Last edited
13/04/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Hemodialysis is a process to remove waste products and excess fluid from the blood when the kidneys stop working properly. Blood pressure (BP) increase during or immediately after hemodialysis is an abnormal response and occurs in 5-15% of hemodialysis patients.
This is linked with harmful clinical outcomes and is often poorly diagnosed and controlled. The exact cause and effect background of high BP during hemodialysis are not yet fully explained and few studies have been designed to evaluate interventions for the management of this.
This study aims to evaluate the effects of a single or weekly dose of two drugs (irbesartan and nebivolol) on 24-hour BP in hemodialysis patients.

Who can participate?
Adults aged over 18 years with end-stage renal disease

What does the study involve?
Participants receive the study drugs in one of two different modes. Those in the first mode receive a single dose of the drug one hour before dialysis. Those in the second mode receive a dose once a day for a week before the evaluation. Participants are assessed at three occasions: once before any treatment has started, once after receiving the first drug, and once after receiving the second drug. The order of the drugs (nebivolol or irbesartan) is randomly decided.
There is a two week period in between these two drugs where the participants do not take any drug known as a wash out period. At each assessment participants have their blood pressure measured over a 24 hour period, and have a blood sample taken before and after dialysis.

What are the possible benefits and risks of participating?
Possible benefits of the study for the patients are to identify an antihypertensive agent that is mostly appropriate for the management of their hypertension. Possible risks include side-effects of the study drugs, which are commonly used antihypertensive agents.

Where is the study run from?
1. AHEPA Hospital, Aristotle University of Thessaloniki (Greece)
2. Hippokration Hospital, Aristotle University of Thessaloniki (Greece)

When is the study starting and how long is it expected to run for?
May 2014 – April 2018

Who is funding the study?
Investigator initiated and funded - the primary investigator is supported by an annual scholarship from the Hellenic Society of Hypertension.

Who is the main contact?
Dr Athanasios Bikos (Scientific)

Trial website

Contact information

Type

Scientific

Primary contact

Dr Athanasios Bikos

ORCID ID

Contact details

Department of Nephrology
Hippokration Hospital
Aristotle University of Thessaloniki
Konstantinoupoleos 49
Thessaloniki
54642
Greece

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

4823/25.2.2013

Study information

Scientific title

This study examines whether in hemodialysis patients with intradialytic hypertension (P) a single or weekly administration of irbesartan or nebivolol (I) compared to no drug administration (C) reduces peridialytic, intradialytic and ambulatory BP levels, as well as ambulatory arterial stiffness parameters (O).

Acronym

Study hypothesis

H0:
Ambulatory BP levels in patients with intradialytic hypertension is not different after administration of irbesartan or nebivolol compared to no drug administration.
H1:
Ambulatory BP levels in patients with intradialytic hypertension is different after administration of irbesartan or nebivolol compared to no drug administration.

Ethics approval

Ethics Committee of the School of Medicine Aristotle University of Thessaloniki, 07/06/2016, ref: 313/7.6.2016

Study design

Pragmatic pilot multi-centre open label randomized cross-over study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Patients with end-stage renal disease on hemodialysis with intradialytic hypertension

Intervention

Each participant is evaluated on three different occasions, starting prior to a mid-week hemodialysis session (e.g. the second weekly session, Wednesday or Thursday). Participants receive the study drugs in one of two different modes. Those in the first group receive a single drug dose one hour prior to dialysis session. Those in the second group receive a once daily dose of the study drug for a whole week.
Baseline evaluation is before a standard hemodialysis session with no treatment.
After baseline evaluation, participants are randomly assigned to receive nebivolol 5 mg and subsequently irbesartan 150mg, or vice versa in a cross-over design.
On each occasion, a 24-hour ambulatory-BP-monitoring (ABPM) is performed with the use of a validated ABPM device and blood specimens are acquired for laboratory testing before and after hemodialysis.
A two-week wash-out period takes place before the initiation of the second drug in both modes of administration.

Intervention type

Drug

Phase

Phase IV

Drug names

Irbesartan, Nebivolol

Primary outcome measures

1. Ambulatory brachial BP levels are assessed with the Mobil-O-Graph NG device for ABPM at the three study-points.
2. Ambulatory central BP levels are assessed with the Mobil-O-Graph NG device for ABPM at the three study-points.
3. Ambulatory arterial stiffness parameters (augmentation Index, augmentation pressure and pulse wave velocity) are assessed with the Mobil-O-Graph NG device for ABPM at the three study-points.

Secondary outcome measures

1. Plasma renin activity and aldosterone are measured at the start and the end of each hemodialysis session at the three study-points.
2. Adrenaline and noradrenaline levels are measured at the start and the end of each hemodialysis session at the three study-points.
3. Endothelin and nitric oxide levels are measured at the start and the end of each hemodialysis session at the three study-points.
4. Body weight is measured at the start and the end of each hemodialysis session at the three study-points.
5. Standard peri-dialytic BP measurements are measured at the three study-points.

Overall trial start date

22/05/2014

Overall trial end date

30/04/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Adult aged >18 years
2. End-stage renal disease treated with thrice-weekly maintenance hemodialysis for more than 3 months
3. Intradialytic hypertension (defined as mean intradialytic rise ≥10 mmHg in systolic BP in at least 4 over 6 consecutive hemodialysis sessions)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

38

Participant exclusion criteria

1. Existing comorbidity requiring treatment with a RAS-blocker (i.e. heart failure, acute myocardial infraction e.t.c.)
2. Existing comorbidity requiring treatment with a β-blocker (i.e. heart failure, cardiac arrhythmia, acute myocardial infarction, angina pectoris, etc.)
3. Existing specific contraindications to receive a RAS-blocker (i.e. history of hyperkalemia, angioedema, anaphylactic or allergic reaction)
4. Existing specific contraindications to receive a β-blocker (bradyarrhythmia, chronic obstructive pulmonary disease, asthma, history of anaphylactic or allergic reaction)
5. Antihypertensive treatment with RAS-blockers (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers or renin-inhibitor) or β-blockers in a period less than one month prior to study enrollment.
6. Pre- or post-hemodialysis SBP levels <130mmHg in 4 out of 6 sessions during the two weeks of the diagnosis of intradialytic hypertension
7. Nonfunctional arteriovenous fistula in the contralateral arm of the one used as vascular access for the hemodialysis session that could interfere with proper ABPM recordings.
8. Active malignant disease or other advanced comorbidity resulting in particularly poor prognosis
9. Inability to understand and provide a written informed consent to participate in the study

Recruitment start date

10/06/2016

Recruitment end date

10/10/2017

Locations

Countries of recruitment

Greece

Trial participating centre

AHEPA Hospital, Aristotle University of Thessaloniki
Section of Nephrology and Hypertension 1st Department of Medicine St.Kiriakidis 1
Thessaloniki
54636
Greece

Trial participating centre

Hippokration Hospital, Aristotle University of Thessaloniki
Department of Nephrology Konstantinoupoleos 49
Thessaloniki
54642
Greece

Sponsor information

Organisation

Aristotle University of Thessaloniki School of Medicine

Sponsor details

University Campus
Thessaloniki
54124
Greece

Sponsor type

University/education

Website

www.med.auth.gr

Funders

Funder type

Other

Funder name

Investigator initiated and funded- the primary investigator is supported by an annual scholarship from the Hellenic Society of Hypertension

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a PubMed-indexed peer-reviewed journal.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are not expected to be made available. The study dataset will be held in the Department of Nephrology, Aristotle University of Thessaloniki.

Intention to publish date

31/08/2018

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes