Clinical Trials Register

Summary
EudraCT Number:	2011-005271-16
Sponsor's Protocol Code Number:	2010NE02
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-10-25
Trial results	View 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

UK - MHRA

A.2

EudraCT number

2011-005271-16

A.3

Full title of the trial

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis? A multicentre randomized placebo controlled trial

A.3.1

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

Bicarbonate for older chronic kidney disease patients with acidosis

A.3.2

Name or abbreviated title of the trial where available

Bicarbonate for older Chronic Kidney Disease patients with Acidosis

A.4.1

Sponsor's protocol code number

2010NE02

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN09486651

A.5.4

Other Identifiers

Name:

MREC

Number:

12/ES/0023

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	University of Dundee & NHS Tayside
B.1.3.4	Country	United Kingdom
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	Health Technology Assessment Board, National Institutes of Health Research
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Tayside Clinical Trials Unit
B.5.2	Functional name of contact point	Margaret Band
B.5.3	Address:
B.5.3.1	Street Address	Ninewells Hospital & Medical School, Residency Block, Level 3. George Pirie Way
B.5.3.2	Town/ city	Dundee
B.5.3.3	Post code	DD1 3RY
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01382383993
B.5.6	E-mail	m.band@dundee.ac.uk

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	No
D.2.1.1.1	Trade name	Sodium Bicarbonate
D.2.1.1.2	Name of the Marketing Authorisation holder	Legosan AB
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	Sodium Bicarbonate
D.3.2	Product code	N/A
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	Sodium Bicarbonate
D.3.9.1	CAS number	144-55-8
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	N/A
D.3.9.4	EV Substance Code	AS1
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	500
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic kidney disease stages 4/5 with metabolic acidosis

E.1.1.1

Medical condition in easily understood language

Advanced kidney disease with raised levels of acid in the blood

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10064848
E.1.2	Term	Chronic kidney disease
E.1.2	System Organ Class	100000004857

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 determine whether oral bicarbonate therapy improves physical function and health-related quality of life compared to placebo in older people with Chronic Kidney Disease (CKD) and mild acidosis

E.2.2

Secondary objectives of the trial

To compare the impact of oral bicarbonate therapy against placebo on biochemical markers of chronic kidney disease in older people with CKD and mild acidosis

To assess whether use of oral bicarbonate therapy is associated with an excess of adverse events compared with placebo in older people with CKD and mild acidosis

To estimate the cost-effectiveness of using oral bicarbonate therapy compared with placebo in older people with CKD and mild acidosis

E.2.3

Trial contains a sub-study

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Bone and vascular substudy
Will be performed on subset of 150 patients (those recruited in Dundee and Aberdeen)
To measure response of markers of bone and vascular health to bicarbonate treatment

E.3

Principal inclusion criteria

Aged 60 and over
CKD stages 4 and 5 (measured by estimated glomerular filtration rate < 30ml/min) Serum bicarbonate/CO2 levels of <22mmol/L

E.4

Principal exclusion criteria

Already taking bicarbonate therapy
Documented renal tubular acidosis (a rare, but separate condition)
On dialysis or anticipated to start within 3 months
Severe cognitive impairment precluding written informed consent
Decompensated chronic heart failure
Bisphosphonate therapy
Uncontrolled hypertension (BP>150/90 despite use of four agents unless in the opinion of the local PI there is evidence of adequate BP control from 24 hour BP monitoring, home BP monitoring or primary care BP records)

E.5 End points

E.5.1

Primary end point(s)

Change in Short Physical Performance Battery (SPPB) score between baseline and 12 months

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

E.5.2

Secondary end point(s)

Secondary outcomes (measured at baseline, 3, 6, 12, and 24 months): Change between baseline and follow-up for:

- EuroQol.
- SPPB (baseline, 3,6,24 mths)
- Serum sodium, potassium, magnesium, urea, bicarbonate, calcium, phosphate, alkaline phosphatase, urea, creatinine, albumin, haemoglobin, thyroid function, HbA1c, lipids.
- Cystatin C
- Weight and anthropometric data (mid arm circumference; triceps skinfold thickness; mid thigh circumference)
- Handgrip strength measured using dynamometry.
- Six minute walk test.
- KDQoL kidney-specific measure of health-related quality of life
- Blood pressure
- Markers of bone health: bone-specific alkaline phosphatase and tartrate-resistant acid-phosphatase 5b, PTH, 25OHD and 1,25OHD (baseline, 12 & 24 months)
- B-type natriuretic peptide.(baseline, 12 & 24 months)

We will also collect data from hospital IT systems, primary care IT systems and patient self-report on the following important clinical outcomes:

- Commencement on dialysis
- All-cause mortality (via General Register Office death records)
- Death from end-stage renal failure
- Cardiovascular mortality
- All hospitalizations (via hospital and GP morbidity records; including heart failure, other cardiovascular and renal-related hospitalizations)
- Outpatients and GP visits
- Changes in medication use
- Fractures will be recorded by direct patient report, verified against GP and hospital records
- Falls will be recorded prospectively using the validated falls diary method
- Information on side effects (e.g. nausea, indigestion, ankle oedema) will be sought by patient self-report. Adherence to study medication will be assessed by tablet counting.
-

E.5.2.1

Timepoint(s) of evaluation of this end point

3,6,12 and 24 months

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

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.8.6 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

Last visit of last participant

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1