Condition category
Urological and Genital Diseases
Date applied
04/04/2013
Date assigned
04/04/2013
Last edited
29/02/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
About 1 in 10 people are living with reduced kidney function because mild (early stage) chronic kidney disease (CKD) is common and kidney function reduces with age. Patients with CKD have reduced survival rate due to high rate of heart and blood vessel diseases. Even people with mild CKD have premature stiffening and reduced function of their heart and blood vessels. Our previous research of 112 people with early CKD from a specialist hospital kidney clinic showed that a 'water tablet' called spironolactone improves heart structure and function as well as reduced blood vessel stiffness. This study aims to confirm the findings in people with early CKD managed at general practices.

Who can participate?
The study will recruit 240 adult patients from 20 general practices in South Birmingham area who have estimated kidney function between 30- 59% on the blood test (mild CKD).

What does the study involve?
Patients who are willing to participate in the study will be assigned to receive ‘study medication’, which are either spironolactone or placebo (dummy capsules) at random. Both participants and doctors will not know who is taking which capsules. Blood and urine test, blood pressure and blood vessel stiffness will be measured before starting the ‘study medication’. Blood vessel stiffness is measured by how fast the pulse travels from neck to groin using cuffs which detect pulse on both sites. Participants will be taking the ‘study medication’ for 40 weeks, during which time they will be followed-up and monitored regularly at their local general practices with blood tests, blood pressure measurements and side effect questionnaire. After 40 weeks of receiving the ‘study medication’, all participants will have repeat blood and urine tests, blood pressure and blood vessel stiffness measured. All the tests will be repeated 6 weeks after stopping the ‘study medication’. The total duration of the study is 46 weeks.

What are the possible benefits and risks of participating?
Our previous research study showed that spironolactone improves heart function and reduces hardening of the blood vessels in patients with mild kidney disease in specialist hospital kidney clinic setting. Patients’ participation in this study will contribute to an improved understanding of spironolactone and its effects on blood vessel and kidney disease in the primary care setting. The information gained from this study will also contribute to further studies and may help improve the treatment of people with kidney disease in the future. The most common side effects from spironolactone are diarrhoea, drowsiness, headache, nausea, stomach cramping and vomiting. Such effects are usually mild and temporary and resolve when the drug is stopped. Other less common but serious side effects are severe allergic reactions (rash, hives, itching, difficulty breathing, tightness in the chest, swelling of the mouth, face, lips, or tongue), black, tarry, or bloody stools, change in the amount of urine produced, confusion, dark urine, decreased sexual ability, enlarged breasts in men, irregular or missed menstrual periods, severe or persistent stomach pain, symptoms of abnormal fluid or electrolyte levels (i.e.: fast, slow, or irregular heartbeat, increased thirst, muscle weakness, severe or persistent dry mouth, nausea, or vomiting, severe or persistent dizziness or drowsiness, unusual fatigue or sluggishness, tingling sensation), yellowing of the skin or eyes. With the exception of the blood tests, study procedures should not cause any pain or discomfort. There are small risks of increased levels of salts in the blood, reduced kidney function or low blood pressure with the use of spironolactone, requiring the withdrawal of the study medication. However, the dose of the trial medication is relatively low and all participants will be closely monitored by kidney specialists during study to ensure that those risks are minimised.

Where is the study run from?
The study is run from the local general practices in South Birmingham area

When is the study starting and how long is it expected to run for?
June 2013 to June 2015

Who is funding the study?
National Institute for Health Research - Research for Patient Benefit (UK)

Who is the main contact?
Dr Odettte Chagoury
o.l.chagoury@bham.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Odette Chagoury

ORCID ID

Contact details

Primary Care Clinical Sciences
School of Health and Population Sciences
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
o.l.chagoury@bham.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

13983

Study information

Scientific title

Spironolactone TO Prevent cardiovascular events in early stage Chronic Kidney Disease (CKD): A pilot trial

Acronym

STOP-CKD

Study hypothesis

About 1 in 10 people are living with reduced kidney function because mild (early stage) chronic kidney disease (CKD) is common and kidney function reduces with age. Patients with CKD have reduced survival rate due to high rate of heart and blood vessels diseases. Even people with mild CKD have premature stiffening and reduced function of their heart and blood vessels. Our previous research of 112 people with early CKD from a specialist hospital kidney clinic showed that a 'water tablet' called spironolactone improves heart structure and function as well as reduced blood vessel stiffness. STOP-CKD study aims to confirm the findings in people with early CKD managed at general practices. The study will recruit 240 patients from 10 general practices, who have estimated kidney function between 30-59% on the blood test (mild CKD). Patients who are willing to participate in the study will be assigned to receive 'study tablets', which are either spironolactone or placebo (dummy tablet) at random. Both patients and doctors will not know who is taking which tablets. Blood and urine test, blood pressure and blood vessel stiffness will be measured before starting the tablets. Blood vessel stiffness is measured by how fast the pulse travels from neck to groin using cuffs which detect pulse on both sites. Patients will be taking the tablets for 40 weeks, during which time; they will be followed-up and monitored regularly at their local general practices with blood test, blood pressure measurement and side effect questionnaire. After 40 weeks of receiving the tablets, repeat blood and urine test, blood pressure and blood vessel stiffness will be measured on the patients. After stopping the 'study tablets' at 40 weeks, patients participating in the study will have repeat blood and urine tests, blood pressure and blood vessel stiffness measured at week 46.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=13983

Ethics approval

12/WM/0168

Study design

Randomised double-blinded placebo-controlled interventional trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Early Stage Chronic Kidney Disease

Intervention

Spironolactone 25mg once daily (OD) or Placebo for 40 weeks

Intervention type

Drug

Phase

Not Applicable

Drug names

Spironolactone

Primary outcome measures

Change in carotid-femoral pulse wave velocity measured at baseline and 40 weeks

Secondary outcome measures

1. Change in blood pressure measured at baseline and 40 weeks
2. Change in estimated Glomerular Filtration Rate (eGFR) measured at baseline and 40 weeks
3. Incidence of hyperkalaemia measured at baseline and 40 weeks
4. Incidence of hypotension (<100mmHg or >20mmHg systolic drop on standing) measured at baseline and 40 weeks

Overall trial start date

01/06/2013

Overall trial end date

01/06/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male and female, age over 18 years
2. Diagnosis of CKD stage 3

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 500

Participant exclusion criteria

1. Diabetes Mellitus
2. Terminal disease or felt otherwise unsuitable by their general practitioner
3. Chronic heart failure i.e. a clinical diagnosis or known ejection fraction <55%
4. Atrial fibrillation
5. Alcohol or drug abuse
6. Inability to comply with trial medication and follow-up
7. Documented previous hyperkalaemia or intolerance of spironolactone
8. Documented Addisonian crisis and/or on fludrocortisone
9. Severe hypertension: blood pressure >= 180/110 mmHg
10. Systolic blood pressure < 120mmHg
11. Recent acute kidney injury or hospital admission (within past 6 weeks)
12. Chronic diarrhoea
13. Albumin:creatinine ratio (ACR) >= 70mg/mmol
14. Serum potassium >= 5 mEq/L on screening blood test
15. Concomittant co-trimoxazole medication
16. Concomittant angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker medication
17. Pregnancy

Recruitment start date

01/06/2013

Recruitment end date

01/06/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Birmingham
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

School of Health and Population Sciences
Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

http://www.birmingham.ac.uk/

Funders

Funder type

Government

Funder name

NIHR (UK) - Research for Patient Benefit; Grant Codes: PB-PG-0110-21226

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/24886272
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26916697

Publication citations

  1. Protocol

    Ng KP, Jain P, Heer G, Redman V, Chagoury OL, Dowswell G, Greenfield S, Freemantle N, Townend JN, Gill PS, McManus RJ, Ferro CJ, Spironolactone to prevent cardiovascular events in early-stage chronic kidney disease (STOP-CKD): study protocol for a randomized controlled pilot trial., Trials, 2014, 15, 158, doi: 10.1186/1745-6215-15-158.

  2. Results

    Ng KP, Jain P, Gill PS, Heer G, Townend JN, Freemantle N, Greenfield S, McManus RJ, Ferro CJ, Results and lessons from the Spironolactone To Prevent Cardiovascular Events in Early Stage Chronic Kidney Disease (STOP-CKD) randomised controlled trial, BMJ Open, 2016, 6, 2, e010519, doi: 10.1136/bmjopen-2015-010519.

Additional files

Editorial Notes

29/02/2016: Publication reference added.