SaDial: the adaptive immune response against Staphylococcus aureus in hemoDialysis patients

ISRCTN	ISRCTN14385893
DOI	https://doi.org/10.1186/ISRCTN14385893
Protocol serial number	BB O29/15
Sponsors	Damp Stiftung, University Medicine Greifswald
Funders	Damp Stiftung, University Medicine Greifswald

Submission date: 24/09/2018
Registration date: 02/10/2018
Last edited: 08/05/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Healthy human skin and mucosa is colonized by a variety of protective bacteria and microorganisms. A common component of this skin flora is the bacterium Staphylococcus aureus (S. aureus). Dialysis patients are chronically exposed to S. aureus, due to their frequent stays in dialysis centers, hospitals or rest homes, where this bacterium is common. In dialysis patients, the access point for the dialysis is a potential entry site for S. aureus, in particular when using a central venous catheter instead of an arteriovenous fistula. It has been shown that S. aureus carriers have a lower risk of sepsis in case of an endogenous infection (i.e. by their “own” S. aureus strain).
So far, it has not been possible to develop a vaccine that protects against an infection with S. aureus. The aim of this study is to collect information on the functionality of the immune system in dialysis patients, and a long-term reduction of serious clinical complications due to S. aureus infections.

Who can participate?
Hemodialysis patients in the KfH e.V. outpatient dialysis center in Greifswald, and 20 healthy control patients

What does the study involve?
We will follow a group of 86 hemodialysis patients from an outpatient dialysis center over a 30 month period. We will collect their demographic data and medical history, along with taking blood samples, nasal swabs and swabs from the hemodialysis access site every 6 months. These samples and swabs will be tested for S. aureus. We will then compare this to the results from healthy controls to reveal differences resulting from dialysis. We will also look at connections between demographic data and medical history and S. aureus infection.

What are the possible benefits and risks of participating?
The benefit of participating is that we will identify potential risk factors that make the occurrence of a bacterial infection more likely, especially in dialysis patients. We want to get an overview of the types of bacteria that are involved in infections, and we are also interested in the proportion of resistant S. aureus strains. With this knowledge, we aim to minimize the risk of infection for our patients. There are no known risks of participating in this study.

Where is the study run from?
1. University Medicine Greifswald (Germany)
2. Kuratorium für Dialyse und Nierentransplantation e.V., KfH-Nierenzentrum Greifswald (Germany)

When is the study starting and how long is it expected to run for?
January 2015 to December 2018

Who is funding the study?
1. DAMP Foundation (Germany)
2. University Medicine Greifswald (Germany)

Who is the main contact?
Prof. Dr. med. Sylvia Stracke
sylvia.stracke@uni-greifswald.de

Contact information

Prof Sylvia Stracke
Scientific

Ferdinand-Sauerbruch-Str.
Greifswald
17489
Germany

Study information

Primary study design	Observational
Study design	Observational prospective cohort study
Secondary study design	Cohort study
Study type	Participant information sheet
Scientific title	Mortality and bloodstream infections in hemodialysis patients from an outpatient dialysis center (KfH e.V.) in Greifswald with respect to S. aureus carrier status, colonization density, S. aureus genotyping and host immune response (SaDial-study) compared to the general population of the same geographical region (SHIP-TREND-0)
Study acronym	SaDial
Study objectives	1. The S. aureus genotypes in hemodialysis patients differ from the general population due to frequent contact with medical environment 2. Nasal S. aureus colonisation protects hemodialysis patients from fatal outcome in case of bloodstream infection by S. aureus 3. The host immune response against S. aureus in hemodialysis patients predicts the course and the outcome of S. aureus sepsis
Ethics approval(s)	University Medicine Greifswald, 17/03/2015, internal registration number: BB O29/15
Health condition(s) or problem(s) studied	Staphylococcus aureus bloodstream infection and S. aureus carrier status in hemodialysis patients
Intervention	A cohort of 86 hemodialysis patients are followed over a 30 month period. Patient demographic data and medical history are collected, followed and statistically evaluated. Blood samples, nasal swabs and swabs from the hemodialysis access site are taken every 6 months for a period of 30 months and are tested for Staphylococcus aureus. The pathogens are cultured and further characterised by spa-PCR and DNA microarrays. Patient samples are analysed for S. aureus-specific antibodies using Luminex, and T-cell responses are analysed using Fluorospot. 20 healthy control patients will receive the same treatment as the cohort of hemodialysis patients; however, swabs and blood and serum samples are only take once in 2015 for this group. There is no follow-up period.
Intervention type	Other
Primary outcome measure(s)	1. Overall mortality rates, assessed using Kaplan-Meier analysis after the final sampling 2. Course and severity of bloodstream infection, determined by assessing for symptoms such as leukocytosis, fever and systemic inflammatory response syndrome, and a positive test for S. aureus in blood culture. This was assessed at the time of infection, and 7 and 14 days after
Key secondary outcome measure(s)	1. S. aureus genotype profiles over time, assessed after each 6 month sampling: 1.1. S. aureus spa-types determined by spa-PCR and out coming sequences classified by Ridom software 1.2. Clonal complexes (CC types) of S. aureus determined using S. aureus Genotyping Kit 2.0 from Alere Technologies (now Abbott) 2. S. aureus specific antibody response over time assessed using a multiplex assay and ELISA, with antibodies isolated every 6 months and stored and overall measurement taken once all samples are collected 3. T-cell response over time, assessed by a Fluorospot assay, with T-cells isolated every 6 months and stored and overall measurement taken once all samples are collected
Completion date	31/12/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	106
Total final enrolment	86
Key inclusion criteria	Patients: 1. Hemodialysis patients of an outpatient dialysis centre (KfH e.V.) in Greifswald 2. Voluntary participation Controls: 1. Voluntary participation 2. Aged 50-70 3. Renally healthy 4. In hospital for at least 1 week
Key exclusion criteria	1. Refusal to participate 2. Moving to another town that is not Greifswald
Date of first enrolment	18/06/2015
Date of final enrolment	01/03/2018

Locations

Countries of recruitment

Germany

Study participating centre

KfH-Nierenzentrum Greifswald

Ferdinand-Sauerbruch-Str.
Greifswald
17489
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data could be made available on request after publication.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	06/05/2019	08/05/2019	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

08/05/2019: Total final enrolment and publication reference were added.