Condition category
Urological and Genital Diseases
Date applied
09/11/2019
Date assigned
29/01/2020
Last edited
29/01/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Pregnancy can worsen chronic kidney disease (CKD). Low nitric oxide may stop kidneys coping with pregnancy and by replacing nitrate in the form of a dietary supplement (beetroot juice) we may be able to protect kidney function in pregnancy.

Who can participate?
Pregnant women aged 18 years or above with CKD Stages 2-5

What does the study involve?
This study will recruit pregnant women with CKD to monitor their health during pregnancy and look for any possible associations between those women in whom kidney function worsens during pregnancy and those in who do not have a reduction in kidney function.
Some participants will be asked to drink a beetroot juice supplement daily for the duration of their pregnancy. The study will tell us how many women are willing to take part, how women felt about the trial and whether they were happy to take treatment. We will also look at treatment effects on kidney function and babies’ growth and wellbeing. These measurements will be used to plan a bigger study to test whether treatments can protect kidney function in pregnancy.

What are the possible benefits and risks of participating?
Participating in the observational study may benefit pregnant women with kidney disease in the future. The risks of participating in the observational arm are minimal and relate to time and mild discomfort that may be experienced when taking samples (blood, saliva, tongue scraping). Possible benefits of Orchard Beet include lowering of blood pressure and possible reduction in pregnancy associated kidney function decline and pregnancy complications. The risks are that this treatment may lead to hypotension (low blood pressure), may be unpleasant to take and may have unanticipated side effects. The dietary nitrate has been studied in other pregnant and non-pregnant populations and has been well tolerated and associated with very little risk to participants.

Where is the study run from?
King's College Hospital NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
February 2020 to August 2022

Who is funding the study?
1. Kidney Research UK
2. National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Dr Kate Bramham
kate.bramham@kcl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Kate Bramham

ORCID ID

Contact details

Department of Nephrology
King's College Hospital NHS Foundation Trust
Denmark Hill
London
SE5 9RS
United Kingdom
+44 (0)20 3299 9000
kate.bramham@kcl.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

JFS_RP_008_20170915, CPMS 44456

Study information

Scientific title

Observational cohort with embedded randomised controlled feasibility trial to study pregnancy-associated progression of renal disease

Acronym

ORCHARD

Study hypothesis

Primary Aim:
To establish a cohort of pregnant women with CKD including longitudinal blood, urine, saliva, tongue scraping samples to enable future embedded randomised controlled trials
Secondary Aim:
To determine the relationship between maternal factors and rates of change in maternal renal function, maternal complications and neonatal adverse outcomes
Sub study (ORCHARD-BEET):
The aim of this investigation is to determine the feasibility and acceptability of recruiting pregnant women with chronic kidney disease (CKD) to a trial of an intervention to prevent progression of the disease

Ethics approval

Not provided at time of registration

Study design

Trial within a cohort (embedded randomized controlled feasibility trial)

Primary study design

Other

Secondary study design

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

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

Condition

Progression of chronic kidney disease in pregnancy

Intervention

Eligible women will be identified from GP referral letters, antenatal or outpatient clinic visits and from health professionals on antenatal wards.
During pregnancy, a blood and urine test will be done at the same time as other blood and urine tests required as part of routine antenatal care (a maximum 3 visits in pregnancy and 2 post-partum visits at 6 weeks and 6 months after delivery). There will be at least one blood and urine test in pregnancy from the time informed consent is given.
- Blood and urine samples will be taken by a research midwife/practitioner, processed immediately and then stored at -80°C for future measurements (e.g. plasma nitrate/nitrite concentrations).
Optional samples will be collected for future research projects including:
- Tongue scrapings placed into a sterile sealed container and stored at -80°C for bacterial community profiling using Next-Generation sequencing for future assessment of relationship with oral nitrate conversion to nitrite.
- Salivary samples (x2) will be collected into sterile tubes, and either processed immediately or stored at -80°C for future measurements (e.g. nitrate/nitrite concentrations and enzymatic activity assays).
If a woman delivers at another hospital the research team will attempt to get the relevant information from the maternity unit used with the permission of the woman.
Following delivery, participants will be asked if they can be contacted to give additional blood and urine samples at 6 weeks and 6 months postpartum. This visit can be coordinated with other postnatal appointments or booked separately after delivery.
If the woman is unable or unwilling to give all samples at each visit she will not be excluded from the main study.

Sub study (ORCHARD-BEET):
Women with CKD will be randomised to take dietary nitrate supplement or no treatment and kidney function at 6 months after delivery will be assessed.
Randomisation to Orchard Beet will take place once patient is recruited to the main ORCHARD study. Minimisation randomisation will immediately be performed electronically after data entry to ORCHARD observational study by the local site team with confirmation emails automatically generated to relevant individuals detailing the allocation by King’s Clinical Trials Unit. Minimisation will be used to ensure balance between the groups with respect to study centre (8 centres), highest serum creatinine concentration prior to randomisation (≤90 µmol/L, 91-120 or >120 µmol/L) and gestation at recruitment (<12 weeks, 12-15+6 weeks, 16-19+6 weeks, ≥20 weeks).

Dietary nitrate: 70 mls ‘Beet It Sport shot’; http://beet-it.com/sport
Active ingredient: 400 mg nitrate/ 6.45 mmol nitrate)
Suppliers Name: James White

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

ORCHARD: Recruitment per centre per month (determined from screening /enrolment logs)

Sub-study (ORCHARD-BEET): Recruitment rate of pregnant women with CKD per site per month (determined from screening /enrolment logs)

Secondary outcome measures

ORCHARD study:
1. Maternal factors will be measured using demographic and clinical data obtained from medical notes, patient interview, examination and blood/urine tests at baseline
2. Maternal renal function will be measured using serum creatinine and urine protein measurement (albumin creatinine ratio, protein creatinine ratio OR 24 hour urine protein) at baseline, each trimester, 6 weeks post-partum and 6 months post-partum
3. Maternal complications will be measured using maternal outcomes (mode, timing, indications for and complications of delivery) and adverse events as defined by the protocol and identified with medical notes and patient interview at each trimester visit, 6 weeks post-partum and 6 months post-partum
4. Neonatal adverse outcomes will be measured using review of medical notes at 6 weeks post-partum to assess mode and outcome of delivery, Apgar scores, measures of size and weight, admission to Neonatal ICU or Special Care Unit
Sub study (ORCHARD-BEET):
5. Number of eligible women with CKD will be assessed from recruitment logs
6. Feasibility and acceptability of the intervention to clinicians and women (including reasons for declining, retention during study and participant attitudes) will be measured using by short semi-structured interviews of local principal investigators (face-to-face or by telephone) and acceptability of women will be assessed with “Survey Monkey” questionnaire sent 2-4 weeks after recruitment, 32+0-35+6 weeks’ gestation, 6-12 weeks after delivery asking whether they enjoyed taking their beetroot juice, whether they would be willing to take it in future pregnancies and whether they would recommend it to other pregnant women with chronic kidney disease
7. Adherence and reasons for non-adherence will be measured using daily diaries of participants which are reviewed and entered into an adherence log on the Orchard database at each trimester and 6 weeks post-partum
8. Mean and SD for primary outcome will be estimated to inform sample size for a definitive trial

Overall trial start date

01/09/2017

Overall trial end date

01/08/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

ORCHARD study:
1. Pregnant women with CKD Stages 2-5 including those with renal transplants i.e. pre-pregnancy eGFR <90mls/min/1.73m2 OR pregnancy creatinine >70 µmol/l (or > 80 µmol/l if Black) with no clinical suspicion of acute kidney injury
2. <24+6 weeks’ gestation
3. ≥18 years old
4. Willing and able to provide written informed consent

Sub study (ORCHARD-BEET):
5. Consented to observational ORCHARD study
6. Agreed to be contacted about future research studies

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

114

Participant exclusion criteria

ORCHARD study:
1. Already established on haemodialysis or peritoneal dialysis
2. Multifetal pregnancy
3. Major life-threatening congenital abnormality

Sub study (ORCHARD-BEET):
4. Known allergy to beetroot

Recruitment start date

01/02/2020

Recruitment end date

01/06/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

King's College Hospital NHS Foundation Trust
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Foundation Trust
Trust Offices, Guys Hospital Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

Barts Health NHS Trust
The Royal London Hospital Whitechapel
London
E1 1BB
United Kingdom

Trial participating centre

Manchester University NHS Foundation Trust
Cobbett House Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Nottingham University Hospital NHS Trust
Trust Headquarters Queens Medical Centre Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

University Hospitals Birmingham NHS Trust
Trust HQ, PO Box 9551 Queen Elizabeth Medical Centre Edgbaston
Birmingham West
B15 2TH
United Kingdom

Trial participating centre

Imperial College Heathcare NHS Trust
St Mary's Hospital Praed Street
London
W2 1NY
United Kingdom

Trial participating centre

University Hospitals of Leicester NHS Trust
Leicester Royal Infirmary Infirmary Square
Leicester
LE1 5WW
United Kingdom

Sponsor information

Organisation

King’s College Hospital NHS Foundation Trust

Sponsor details

The R&I Office
161 Denmark Hill
London
SE5 9RS
United Kingdom
+44 (0)20 3299 1980
kch-tr.research@nhs.net

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Kidney Research UK

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The research team plans to disseminate the study research findings in the following settings:
- Conference presentation of study process and results at UK Kidney Week, American Society of Nephrology Conference or the European Renal Association conference and related Obstetric Conferences including British Maternal and Fetal Medicine Society and International Society of Nephrology.
- Publication of results in a renal or obstetric specific recognised impact journal

The protocol and SAP will be available on request from the study contact below.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are/will be available upon request from the Chief Investigator, Dr Kate Bramham (kate.bramham@kcl.ac.uk).
- Type of data: Fully anonymised individual patient demographic and clinical data
- Suitable for all types of analyses conditional on ethics approval and approval by the Orchard Trial Group
- Mechanism: Obtain REC approval for study, contact Dr Bramham, request considered by Orchard Trial Group and if deemed appropriate then data sharing agreement drafted and requested data transferred
- Consent: Will be sought from Orchard participants at recruitment for their data to be used in future studies subject to ethics approval

Intention to publish date

01/08/2022

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

06/12/2019: Trial’s existence confirmed by Kidney Research UK