Condition category
Urological and Genital Diseases
Date applied
23/01/2017
Date assigned
26/01/2017
Last edited
26/01/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
People who receive a kidney transplant need to take medication that suppresses the body’s immune system (the body’s defense mechanism) in order to make sure their body does not reject the new kidney. These medications, known as immunosuppressant drugs, can lead to serious side effects such as infections and increases in cardiovascular risk (risk of heart attack or stroke). In order to help kidney transplant patients, the monitoring of immunosuppressive medication needs to be improved. New tools have been developed in order to monitor how well the medication works as the standard monitoring tools are not able to directly measure the effects of the medication in individual patients. The aim of this study is to compare the normal method of monitoring immunosuppressive medication (cyclosporin A (CsA)) to the new monitoring tool to see if it improves patient’s health and lowers their cardiovascular risk.
Who can participate?
Adults who have received a kidney transplant and are receiving immunosuppressive medication

What does the study involve?
Participants are randomly allocated to one of two groups. The first group receives standard monitoring of their immunosuppressive medication CsA. This includes a blood test done prior to taking the medication in order to measure the amount of CsA found in the blood. The second group receives the new monitoring process, which includes a blood test done prior to taking the medication and again two hours later in order to compare specific markers in the blood to see how well CsA is working. At the start of the study and again after six months, participants have their cardiovascular risk measured. At the start of the study and again after one, three and six months, participants have blood tests to check for signs of organ rejection.

What are the possible benefits and risks of participating?
There are no direct benefits of participants however it can help improve immunosuppressive medications for them in the future. There are no notable risks to participants other than discomfort from blood tests.

Where is the study run from?
Renal Center Heidelberg (Germany)

When is the study starting and how long is it expected to run for?
August 2011 to December 2014

Who is funding the study?
Renal Center Heidelberg (Germany)

Who is the main contact?
Dr Claudia Sommerer

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Claudia Sommerer

ORCID ID

Contact details

University Hospital Heidelberg
Department of Nephrology
Im Neuenheimer Feld 162
Heidelberg
69120
Germany

Additional identifiers

EudraCT number

2011-003547-21

ClinicalTrials.gov number

Protocol/serial number

RCHD–CsA1004

Study information

Scientific title

A randomized open-label trial to evaluate the cardiovascular risk in stable renal allograft recipients on a ciclosporin A (CsA) based regimen monitored either by residual expression of nuclear factor of activated T-cells (NFAT) – regulated genes or CsA trough levels

Acronym

The CIS Study

Study hypothesis

Monitoring of ciclosporin A therapy by residual nuclear factor of activated T-cell (NFAT)-regulated gene expression (RGE) is superior to standard C0 monitoring in terms of pulse wave velocity, an established sensitivity marker for the assessment of cardiovascular risk.

Ethics approval

Independent Ethics Committee of Institution University Hospital Heidelberg Ethikkommission, 31/05/2013, ref: AFmo-622/2012

Study design

Single-centre prospective randomised controlled parallel-group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Other

Patient information sheet

No participant information sheet available in English language.

Condition

Renal transplantation

Intervention

Participants are enrolled consecutively after providing written informed consent. Randomization is performed in a 1:1 ratio by a web-based validated randomization tool and are allocated to one of two groups. All participants receive ciclosporin A (CsA) and mycophenolic acid in the standard dosage.

Standard Monitoring Group:
Participants receive CsA orally, at a dose adjusted to reach the specified exposure target CsA CO levels of 80 to 150 μg/L. This therapy is monitored by the CsA CO monitoring (80-150 ng/ml), which means blood samples are taken from participants in the morning before medication is ingested and the level of CsA concentration is measured. Adjustment to the CsA dosages are made if necessary at each study visit (baseline, month 1, month 3, month 6 and end of study) due to adverse events.

Investigation Group:
Participants receive CsA orally at a dose adjusted to to the results of the new monitoring tool. The CsA therapy is monitored by activated T-cell (NFAT)-regulated gene expression (RGE) of 15 to 30%. The expression of the NFAT-regulated genes (interleukin 2, granulocyte-macrophage colony stimulating-factor, interferon- y) is determined by qRT-PCR at CsA CO and C2. This means that blood is taken in the morning prior to the medication being ingested and then two hours after. Cytokine gene expression is measured in these samples. Adjustment to the CsA dosages are made if necessary at each study visit (baseline, month 1, month 3, month 6 and end of study) due to adverse events.

Following the study, participants receive CsA according to their local center practice. All participants are followed regularly at the end of the study.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Cardiovascular risk is assessed by measuring pulse wave velocity by measuring pulse wave velocity by SphygmoCor at baseline and at 6 months.

Secondary outcome measures

1. Aortic pulse pressure and central blood pressure is measured using SphygmoCor at baseline and 6 months
2. Blood pressure is measured using a sphygmomanometer at baseline and 6 months
3. Glucose is measured by enzymatic method at baseline and 6 months
4. Cholesterol (LDL and HDL cholesterol) is enzymatic method measured by at baseline and 6 months
5. Triglyceride is measured by enzymatic method at baseline and 6 months
6. S-creatinine is measured by enzymatic method at baseline and 6 months
7. Proteinuria is measured by enzymatic method at baseline and 6 months
8. Myocardial infarction is assessed through reviewing patient’s records at baseline, 1 month, 3 months, and 6 months
9. Apoplexy is assessed through reviewing patient’s records at baseline, 1 month, 3 months, and 6 months
10. Peripheral arterialocclusive disease rate is assessed by reviewing patients records at baseline, 1 month, 3 months, and 6 months
11. Ciclosporin A induced side effects are assessed through reviewing patient’s records at baseline, 1 month, 3 months, and 6 months
12. Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SEAs) are assessed by reviewing patient notes at baseline, 1 month, 3 months, and 6 months
13. Renal allograft function is assessed by measuring S-creatinine (enzymatic method, standard lab) and 7-MDRD formula at baseline, 1 month, 3 months, and 6 months
14. Biopsy proven acute rejections (classified by BANFF criteria), graft loss, death, and loss-to-follow-up are assessed by reviewing patient notes at baseline, 1 month, 3 months, and 6 months

Overall trial start date

10/08/2011

Overall trial end date

31/12/2014

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Over the age of 18 years old
2. Received a renal allograft from a deceased or living donor at least six months prior to study entry
3. Stable renal allograft function, defined as serum S-creatinine ≤ 3.•5 mg/dL and Δ serum S-creatinine ≤ 30% during the previous last three months
4. Receiving CsA microemulsion, mycophenolic acid, and steroids

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

55

Participant exclusion criteria

1. History of biopsy-proven acute rejection classified as Banff grade ≥ II
2. Chronic active antibody-mediated rejection
3. Chronic T-cell mediated rejection prior to enrollment

Recruitment start date

23/10/2013

Recruitment end date

01/06/2014

Locations

Countries of recruitment

Germany

Trial participating centre

University Hospital Heidelberg
Department of Nephrology Renal Center Heidelberg Im Neuenheimer Feld 162
Heidelberg
69120
Germany

Sponsor information

Organisation

Renal Center Heidelberg

Sponsor details

Im Neuenheimer Feld 162
Heidelberg
69120
Germany

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

Renal Center Heidelberg

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD sharing plan:
The current data sharing plans for the current study are unknown and will made available at a later date.

Intention to publish date

31/12/2018

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes