SepsisNCT06963853
Evaluation of Microbial and Endocrinological Parameters in Dialysis Patients With Sepsis
An observational study of Sepsis and Hemodialysis, run by Western Galilee Hospital-Nahariya at 1 site in Israel.
Trial summary
This prospective study aims to evaluate the diagnostic value and reliability of blood cultures obtained from different sources-central venous catheter (CVC), dialysis machine, and peripheral vein-in hemodialysis patients with suspected catheter-related bloodstream infections (CRBSIs). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Hemodialysis
- What is being tested?
- Blood cultures will be obtained from three sources: 1. The central venous catheter (CVC), 2. The dialysis machine circuit, and 3. A peripheral vein
- How many people
- 200 participants
- Where
- 1 siteIsrael
- Study dates
- 16 Aug 2022to Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Hemodialysis patients over the age of 18 who are hospitalized at the Galilee Medical Center due to sepsis and have provided written informed consent to participate in this study.
Inclusion Criteria: hemodialysis patients over the age of 18 who are hospitalized at the Galilee Medical Center due to sepsis and have provided written informed consent to participate in this study.
-
Exclusion Criteria: • Patients with cognitive impairment who are unable to provide informed consent.
-
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Galilee Medical Center
Nahariya, Israel, 2210001
Etty Kruzel-Davila, Head of the Nephrology Depart, 972-4-9107619, ETTYK@gmc.gov.il
Olga Vdovich, MD, 972-4-9107603, olgav@gmc.gov.il
About this study
This prospective study aims to evaluate the diagnostic value and reliability of blood cultures obtained from different sources-central venous catheter (CVC), dialysis machine, and peripheral vein-in hemodialysis patients with suspected catheter-related bloodstream infections (CRBSIs). By comparing the timing and rates of bacterial growth from each site, the study seeks to identify the most accurate and timely method for diagnosing bloodstream infections in this patient population.
In addition, the study will assess the dynamics of parathyroid hormone (PTH) levels during acute infections. Specifically, it will investigate whether a significant drop in PTH levels-and the rate of recovery following infection-correlates with adverse outcomes such as infectious complications, cardiovascular morbidity, or 90-day mortality. These findings may offer valuable prognostic insights and support improved monitoring and treatment strategies for dialysis patients experiencing infection.
Read the detailed description
Chronic kidney disease (CKD) is a major global public health challenge, affecting millions of individuals worldwide. A significant proportion of these patients progress to end-stage kidney disease (ESKD), necessitating renal replacement therapies such as hemodialysis (HD). Beyond the gradual decline in renal function, CKD is associated with a high burden of comorbidities, particularly cardiovascular disease (CVD) and infections .Patients with CKD undergoing hemodialysis are especially vulnerable to infections, which represent a major contributor to morbidity and mortality in this population. This increased susceptibility is largely attributable to secondary immunodeficiency associated with kidney disease (SIDKD), the repeated need for vascular access, and the presence of multiple coexisting conditions.
Vascular access through catheters, grafts, or fistulas is essential for dialysis treatment. According to the 2023 USRDS report, in 2021, over 85% of individuals who began hemodialysis initiated treatment using a central venous catheter (CVC). Patients undergoing hemodialysis with a central venous catheter (CVC) are at increased risk for catheter-related bloodstream infections (CRBSIs), which are associated with significant morbidity, including a higher incidence of cardiovascular events, increased mortality, and substantial healthcare costs.6-10 The incidence of catheter-related infections has been reported to range from 1.1 to 5.5 episodes per 1,000 CVC days.
A retrospective study reported a median time of 163 days to the first episode of CRBSI.13 Several studies have identified a range of risk factors associated with CRBSI in hemodialysis patients. These include diabetes mellitus, age under 75 years, prolonged use of tunneled or implanted catheters, immunosuppressive therapy, colonization with methicillin-resistant Staphylococcus aureus (MRSA), and a history of bacteremia or bacteriuria within three months prior to catheter insertion. Additional factors include dialysis vintage, the site of catheter placement, number of catheterizations and abnormal laboratory parameters such as low albumin, elevated C-reactive protein (CRP), and reduced hemoglobin levels.
Diagnosis of CRBSI is challenging, as not all bacteremia in dialysis patients originates from catheters.
Diagnosis requires at least 1 positive blood culture from a peripheral source (dialysis circuit or vein) and no other apparent source, with either positive semiquantitative (>15 CFU/ catheter segment, hub or tip) or quantitative (>102 CFU/catheter segment, eg, hub or tip) culture, whereby the same organism (species and antibiogram) is isolated from the catheter segment (eg, hub or tip) and a peripheral source (dialysis circuit or vein) blood sample. If available, the following would be supportive: Simultaneous quantitative cultures of blood samples with a ratio of ≥3:1 (catheter hub/tip vs peripheral [dialysis circuit/vein]); differential period of catheter culture versus peripheral BC positivity of 2 hours. According to the Centers for Disease Control and Prevention (CDC), a compatible clinical presentation, along with at least one positive peripheral blood culture and no other identifiable source of infection, combined with growth of the same organism from a tunneled catheter tip, either positive semiquantitative culture (>15 CFU/catheter segment) or quantitative culture (>10³ CFU/catheter segment), supports the diagnosis of a catheter-related infection.
However, peripheral venous access is often limited in dialysis patients due to the need to preserve veins for future vascular access creation. Due to the challenges associated with obtaining peripheral venous blood samples, a study conducted in Canada compared the results of peripheral blood cultures to cultures taken from tunneled catheters and from the dialysis machine during treatment. This study demonstrated that blood cultures drawn from the dialysis circuit during treatment had higher sensitivity and specificity for detecting catheter-related bloodstream infections compared to peripheral blood cultures. Despite these findings, current guidelines for evaluating catheter-related bloodstream infections have not changed, and there is still a recommendation to obtain catheter hub/tip vs peripheral [dialysis circuit/vein]).
Parathyroid hormone (PTH) may influence immune function, yet data on PTH fluctuations during infections in dialysis patients are limited. Studies suggest low PTH levels are associated with recurrent infections and increased mortality.
Fluctuations in parathyroid hormone (PTH) levels during infection may be driven by elevated levels of pro-inflammatory cytokines such as IL-6 and IL-1β, which upregulate the expression of calcium-sensing receptors (CaSR) on the parathyroid gland, thereby leading to suppressed PTH secretion.
In critically ill patients, including those with septic shock or extensive burns, hypocalcemia has been frequently observed. This phenomenon may be partially explained by the presence of high extracellular calcium concentrations in necrotic tissues, which can stimulate pro-inflammatory cytokine release and activate the CaSR, contributing to inflammation-induced hypocalcemia. Notably, CaSR has been proposed to function as a chemokine-like receptor, promoting inflammatory responses and cytokine recruitment.
In addition to its role in calcium-phosphate homeostasis, PTH is known to modulate immune function. Elevated PTH levels promote T-lymphocyte proliferation and IL-2 secretion, whereas suppressed PTH levels-particularly below 65 pg/mL-have been associated with reduced CD4/CD8 ratios and increased susceptibility to infections in dialysis patients.
Moreover, low PTH levels have been linked to malnutrition and the development of malnutrition-inflammation complex syndrome (MICS), a condition commonly observed in the dialysis population.
Despite the biological rationale outlined above, it remains unclear whether PTH levels fluctuate during infection and whether such changes carry prognostic significance. A clinical observation in the dialysis unit at the Galilee Medical Center led to the hypothesis that PTH levels decrease during episodes of sepsis.
This study aims to characterize whether a significant decline in PTH levels occurs during sepsis, while simultaneously evaluating additional metabolic parameters such as white blood cell count, hemoglobin, platelets, calcium, phosphate, albumin, and CRP. Furthermore, we plan to assess the rate of PTH recovery following clinical resolution of infection and explore its potential association with clinical outcomes, including recurrent infections, cardiovascular morbidity, and mortality.
Research Hypothesis:
- In hemodialysis patients with catheter-related bloodstream infections, blood cultures drawn from the dialysis machine are expected to detect infection as effectively, or possibly more effectively, than peripheral venous blood cultures.
- Changes in parathyroid hormone (PTH) levels may indicate an increased risk of mortality, potentially informing treatment adjustments and monitoring strategies in dialysis patients with acute infections.
Study Objectives:
- To compare the diagnostic yield of blood cultures obtained from three different sources in hemodialysis patients:
- Central venous catheter (CVC),
- Dialysis machine (during treatment),
- Peripheral vein.
- To measure PTH levels during sepsis and compare them to baseline pre-infection levels, with serial follow-up of PTH values post-recovery.
- To assess clinical outcomes including infectious and cardiovascular complications, and mortality, in correlation with PTH levels in patients experiencing sepsis.
- Conditions
- Sepsis, Hemodialysis
- Being tested
- Blood cultures will be obtained from three sources: 1. The central venous catheter (CVC), 2. The dialysis machine circuit, and 3. A peripheral vein
- Keywords
- blood cultures, parathyroid hormone, catheter, infection, cardiovascular, mortality
- Medical subject headings
- Sepsis, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood cultures will be obtained from three sources: 1. The central venous catheter (CVC), 2. The dialysis machine circuit, and 3. A peripheral veinDiagnostic test
PTH levels during sepsis and compare them to baseline pre-infection levels, with serial follow-up of PTH values post-recovery.
| Study group | Role | What they receive |
|---|---|---|
| Hemodialysis patients with suspected catheter-related bloodstream infections (CRBSIs). | Study Population:
The study will include hemodialysis patients over the age of 18 who are hospitalized at the Galilee Medical Center due to sepsis and have provided written informed consent to participate in this study.
Study Procedure:
During hospitalization, and as part of the clinical workup for sepsis, blood cultures will be obtained from three sources:
1. The central venous catheter (CVC),
2. The dialysis machine circuit, and
3. A peripheral vein. In addition, parathyroid hormone (PTH) levels will be measured through a blood sample. Receives: Diagnostic Test: Blood cultures will be obtained from three sources: 1. The central venous catheter (CVC), 2. The dialysis machine circuit, and 3. A peripheral vein |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Positive Blood Cultures by Sampling Site Among Documented Bloodstream Infections (CVC, Dialysis Machine, Peripheral Vein)
This outcome measure will compare the proportion of positive blood cultures obtained from three different sampling sites-central venous catheter (CVC), dialysis machine, and peripheral vein-among all confirmed cases of bloodstream infection in dialysis patients. The goal is to evaluate the diagnostic yield of each site and identify the most sensitive and reliable source for detecting bloodstream infections. Findings will support evidence-based recommendations regarding the preferred site for blood culture collection in this population. Comparative analysis will include statistical evaluation of sensitivity, yield, and agreement between sites.
Measured: Within 21 days of hospitalization
Change in Parathyroid Hormone (PTH) Levels During Infection and Rate of PTH Recovery Post-Discharge
This outcome measure will evaluate the change in parathyroid hormone (PTH) levels during acute infection and the monthly rate of recovery after hospital discharge in dialysis patients. PTH levels will be measured at three time points: (1) during the acute infection, (2) at discharge, and (3) monthly for up to 90 days post-discharge. The primary analysis will assess the magnitude of PTH suppression during infection and the trajectory of recovery over time. These parameters will be analyzed for their correlation with key 90-day outcomes, including infectious complications, cardiovascular events, and all-cause mortality. Statistical analyses will include repeated measures ANOVA and mixed-effects models to evaluate longitudinal changes and their association with clinical endpoints.
Measured: 90 days post-discharge
Secondary outcomes (3)
Rate of Recurrent Infections Within 90 Days of Hospital Discharge
This secondary outcome will assess the rate of recurrent infections occurring within 90 days of hospital discharge among dialysis patients who experienced an initial infectious episode. The analysis will examine whether the magnitude of PTH suppression during infection and the rate of PTH recovery post-discharge are associated with the risk of recurrent infection. Recurrent infections will be defined based on clinical and microbiological criteria. Statistical analysis will include logistic regression and time-to-event models.
Measured: 90 days post-discharge
Incidence of Cardiovascular Events Within 90 Days of Hospital Discharge
This secondary outcome will assess the incidence of cardiovascular events occurring within 90 days of discharge among dialysis patients following an infectious episode. The analysis will explore whether the degree of parathyroid hormone (PTH) suppression during infection and the rate of PTH recovery are associated with cardiovascular risk. Cardiovascular events will include acute coronary syndrome, arrhythmia, stroke, and heart failure exacerbation, confirmed by clinical documentation. Statistical models such as Cox proportional hazards or logistic regression will be used to evaluate associations.
Measured: 90 days post-discharge
All-Cause Mortality Within 180 Days of Hospital Discharge.
This secondary outcome will evaluate all-cause mortality within 180 days following hospital discharge in dialysis patients who experienced an infectious episode. The analysis will investigate whether the extent of parathyroid hormone (PTH) suppression during infection and the rate of PTH recovery post-discharge are associated with mortality risk. Deaths will be confirmed through clinical records or national registries. Cox proportional hazards models will be used to assess the relationship between PTH dynamics and mortality.
Measured: 180 days post-discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2025
- Study start16 Aug 2022
- Primary completionJan 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Western Galilee Hospital-Nahariya
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Etty Kruzel-Davila, Western Galilee Hospital-Nahariya
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06963853
- Sponsor's protocol ID
- 0086-22-NHR
- Status last verified
- May 2025
- First submitted
- 30 Apr 2025
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The following individual participant data (IPD) will be shared: Demographic information (age, sex, dialysis vintage) Clinical data relevant to the study (reason for hospitalization, comorbidities, dialysis modality) Blood culture results from all sampling sites (central catheter, dialysis machine, peripheral vein) Laboratory values, including PTH levels at baseline and during infection Outcome data, including complications during hospitalization, cardiovascular events, and 90-day mortality All shared data will be de-identified to protect patient confidentiality, in compliance with relevant privacy regulations and ethical guidelines.
Publications
Dukkipati R, Kovesdy CP, Colman S, Budoff MJ, Nissenson AR, Sprague SM, Kopple JD, Kalantar-Zadeh K. Association of relatively low serum parathyroid hormone with malnutrition-inflammation complex and survival in maintenance hemodialysis patients. J Ren Nutr. 2010 Jul;20(4):243-54. doi: 10.1053/j.jrn.2009.10.006. Epub 2010 Mar 3.
PubMed 20199875Ozdemir FN, Yakupoglu U, Turan M, Arat Z, Karakayali H, Erdal R, Turan M. Role of parathormone levels on T-cell response in hemodialysis patients. Transplant Proc. 2002 Sep;34(6):2044-5. doi: 10.1016/s0041-1345(02)02846-4. No abstract available.
PubMed 12270308Canaff L, Zhou X, Hendy GN. The proinflammatory cytokine, interleukin-6, up-regulates calcium-sensing receptor gene transcription via Stat1/3 and Sp1/3. J Biol Chem. 2008 May 16;283(20):13586-600. doi: 10.1074/jbc.M708087200. Epub 2008 Mar 17.
PubMed 18348986Hendy GN, Canaff L. Calcium-sensing receptor, proinflammatory cytokines and calcium homeostasis. Semin Cell Dev Biol. 2016 Jan;49:37-43. doi: 10.1016/j.semcdb.2015.11.006. Epub 2015 Nov 21.
PubMed 26612442Hong YA, Kim JH, Kim YK, Chang YK, Park CW, Kim SY, Kim YS, Kang SW, Kim NH, Kim YL, Yang CW. Low parathyroid hormone level predicts infection-related mortality in incident dialysis patients: a prospective cohort study. Korean J Intern Med. 2020 Jan;35(1):160-170. doi: 10.3904/kjim.2018.264. Epub 2019 Oct 28.
PubMed 31648433Quittnat Pelletier F, Joarder M, Poutanen SM, Lok CE. Evaluating Approaches for the Diagnosis of Hemodialysis Catheter-Related Bloodstream Infections. Clin J Am Soc Nephrol. 2016 May 6;11(5):847-854. doi: 10.2215/CJN.09110815. Epub 2016 Apr 1.
PubMed 27037271O'Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, Lipsett PA, Masur H, Mermel LA, Pearson ML, Raad II, Randolph AG, Rupp ME, Saint S; Healthcare Infection Control Practices Advisory Committee (HICPAC) (Appendix 1). Summary of recommendations: Guidelines for the Prevention of Intravascular Catheter-related Infections. Clin Infect Dis. 2011 May;52(9):1087-99. doi: 10.1093/cid/cir138. No abstract available.
PubMed 21467014Guo H, Zhang L, He H, Wang L. Risk factors for catheter-associated bloodstream infection in hemodialysis patients: A meta-analysis. PLoS One. 2024 Mar 27;19(3):e0299715. doi: 10.1371/journal.pone.0299715. eCollection 2024.
PubMed 38536779Delistefani F, Wallbach M, Muller GA, Koziolek MJ, Grupp C. Risk factors for catheter-related infections in patients receiving permanent dialysis catheter. BMC Nephrol. 2019 May 31;20(1):199. doi: 10.1186/s12882-019-1392-0.
PubMed 31151433Hoen B, Paul-Dauphin A, Hestin D, Kessler M. EPIBACDIAL: a multicenter prospective study of risk factors for bacteremia in chronic hemodialysis patients. J Am Soc Nephrol. 1998 May;9(5):869-76. doi: 10.1681/ASN.V95869.
PubMed 9596085Murea M, James KM, Russell GB, Byrum GV 3rd, Yates JE, Tuttle NS, Bleyer AJ, Burkart JM, Freedman BI. Risk of catheter-related bloodstream infection in elderly patients on hemodialysis. Clin J Am Soc Nephrol. 2014 Apr;9(4):764-70. doi: 10.2215/CJN.07710713. Epub 2014 Mar 20.
PubMed 24651074Martin K, Lorenzo YSP, Leung PYM, Chung S, O'flaherty E, Barker N, Ierino F. Clinical Outcomes and Risk Factors for Tunneled Hemodialysis Catheter-Related Bloodstream Infections. Open Forum Infect Dis. 2020 Apr 11;7(6):ofaa117. doi: 10.1093/ofid/ofaa117. eCollection 2020 Jun.
PubMed 32550235Shingarev R, Barker-Finkel J, Allon M. Natural history of tunneled dialysis catheters placed for hemodialysis initiation. J Vasc Interv Radiol. 2013 Sep;24(9):1289-94. doi: 10.1016/j.jvir.2013.05.034. Epub 2013 Jul 18.
PubMed 23871694Lok CE, Foley R. Vascular access morbidity and mortality: trends of the last decade. Clin J Am Soc Nephrol. 2013 Jul;8(7):1213-9. doi: 10.2215/CJN.01690213.
PubMed 23824198Ravani P, Gillespie BW, Quinn RR, MacRae J, Manns B, Mendelssohn D, Tonelli M, Hemmelgarn B, James M, Pannu N, Robinson BM, Zhang X, Pisoni R. Temporal risk profile for infectious and noninfectious complications of hemodialysis access. J Am Soc Nephrol. 2013 Oct;24(10):1668-77. doi: 10.1681/ASN.2012121234. Epub 2013 Jul 11.
PubMed 23847278
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Microbial and Endocrinological Parameters in Dialysis Patients With Sepsis
- ClinicalTrials.gov ID
- NCT06963853
- Acronym / sponsor ID
- 0086-22-NHR
- Conditions
- Sepsis, Hemodialysis
- Keywords
- blood cultures, parathyroid hormone, catheter, infection, cardiovascular, mortality
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Western Galilee Hospital-NahariyaOther government
- Study start
- 16 Aug 2022 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 9 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This prospective study aims to evaluate the diagnostic value and reliability of blood cultures obtained from different sources-central venous catheter (CVC), dialysis machine, and peripheral vein-in hemodialysis patients with suspected catheter-related bloodstream infections (CRBSIs). By comparing the timing and rates of bacterial growth from each site, the study seeks to identify the most accurate and timely method for diagnosing bloodstream infections in this patient population.
In addition, the study will assess the dynamics of parathyroid hormone (PTH) levels during acute infections. Specifically, it will investigate whether a significant drop in PTH levels-and the rate of recovery following infection-correlates with adverse outcomes such as infectious complications, cardiovascular morbidity, or 90-day mortality. These findings may offer valuable prognostic insights and support improved monitoring and treatment strategies for dialysis patients experiencing infection.
Detailed description
Chronic kidney disease (CKD) is a major global public health challenge, affecting millions of individuals worldwide. A significant proportion of these patients progress to end-stage kidney disease (ESKD), necessitating renal replacement therapies such as hemodialysis (HD). Beyond the gradual decline in renal function, CKD is associated with a high burden of comorbidities, particularly cardiovascular disease (CVD) and infections .Patients with CKD undergoing hemodialysis are especially vulnerable to infections, which represent a major contributor to morbidity and mortality in this population. This increased susceptibility is largely attributable to secondary immunodeficiency associated with kidney disease (SIDKD), the repeated need for vascular access, and the presence of multiple coexisting conditions.
Vascular access through catheters, grafts, or fistulas is essential for dialysis treatment. According to the 2023 USRDS report, in 2021, over 85% of individuals who began hemodialysis initiated treatment using a central venous catheter (CVC). Patients undergoing hemodialysis with a central venous catheter (CVC) are at increased risk for catheter-related bloodstream infections (CRBSIs), which are associated with significant morbidity, including a higher incidence of cardiovascular events, increased mortality, and substantial healthcare costs.6-10 The incidence of catheter-related infections has been reported to range from 1.1 to 5.5 episodes per 1,000 CVC days.
A retrospective study reported a median time of 163 days to the first episode of CRBSI.13 Several studies have identified a range of risk factors associated with CRBSI in hemodialysis patients. These include diabetes mellitus, age under 75 years, prolonged use of tunneled or implanted catheters, immunosuppressive therapy, colonization with methicillin-resistant Staphylococcus aureus (MRSA), and a history of bacteremia or bacteriuria within three months prior to catheter insertion. Additional factors include dialysis vintage, the site of catheter placement, number of catheterizations and abnormal laboratory parameters such as low albumin, elevated C-reactive protein (CRP), and reduced hemoglobin levels.
Diagnosis of CRBSI is challenging, as not all bacteremia in dialysis patients originates from catheters.
Diagnosis requires at least 1 positive blood culture from a peripheral source (dialysis circuit or vein) and no other apparent source, with either positive semiquantitative (>15 CFU/ catheter segment, hub or tip) or quantitative (>102 CFU/catheter segment, eg, hub or tip) culture, whereby the same organism (species and antibiogram) is isolated from the catheter segment (eg, hub or tip) and a peripheral source (dialysis circuit or vein) blood sample. If available, the following would be supportive: Simultaneous quantitative cultures of blood samples with a ratio of ≥3:1 (catheter hub/tip vs peripheral [dialysis circuit/vein]); differential period of catheter culture versus peripheral BC positivity of 2 hours. According to the Centers for Disease Control and Prevention (CDC), a compatible clinical presentation, along with at least one positive peripheral blood culture and no other identifiable source of infection, combined with growth of the same organism from a tunneled catheter tip, either positive semiquantitative culture (>15 CFU/catheter segment) or quantitative culture (>10³ CFU/catheter segment), supports the diagnosis of a catheter-related infection.
However, peripheral venous access is often limited in dialysis patients due to the need to preserve veins for future vascular access creation. Due to the challenges associated with obtaining peripheral venous blood samples, a study conducted in Canada compared the results of peripheral blood cultures to cultures taken from tunneled catheters and from the dialysis machine during treatment. This study demonstrated that blood cultures drawn from the dialysis circuit during treatment had higher sensitivity and specificity for detecting catheter-related bloodstream infections compared to peripheral blood cultures. Despite these findings, current guidelines for evaluating catheter-related bloodstream infections have not changed, and there is still a recommendation to obtain catheter hub/tip vs peripheral [dialysis circuit/vein]).
Parathyroid hormone (PTH) may influence immune function, yet data on PTH fluctuations during infections in dialysis patients are limited. Studies suggest low PTH levels are associated with recurrent infections and increased mortality.
Fluctuations in parathyroid hormone (PTH) levels during infection may be driven by elevated levels of pro-inflammatory cytokines such as IL-6 and IL-1β, which upregulate the expression of calcium-sensing receptors (CaSR) on the parathyroid gland, thereby leading to suppressed PTH secretion.
In critically ill patients, including those with septic shock or extensive burns, hypocalcemia has been frequently observed. This phenomenon may be partially explained by the presence of high extracellular calcium concentrations in necrotic tissues, which can stimulate pro-inflammatory cytokine release and activate the CaSR, contributing to inflammation-induced hypocalcemia. Notably, CaSR has been proposed to function as a chemokine-like receptor, promoting inflammatory responses and cytokine recruitment.
In addition to its role in calcium-phosphate homeostasis, PTH is known to modulate immune function. Elevated PTH levels promote T-lymphocyte proliferation and IL-2 secretion, whereas suppressed PTH levels-particularly below 65 pg/mL-have been associated with reduced CD4/CD8 ratios and increased susceptibility to infections in dialysis patients.
Moreover, low PTH levels have been linked to malnutrition and the development of malnutrition-inflammation complex syndrome (MICS), a condition commonly observed in the dialysis population.
Despite the biological rationale outlined above, it remains unclear whether PTH levels fluctuate during infection and whether such changes carry prognostic significance. A clinical observation in the dialysis unit at the Galilee Medical Center led to the hypothesis that PTH levels decrease during episodes of sepsis.
This study aims to characterize whether a significant decline in PTH levels occurs during sepsis, while simultaneously evaluating additional metabolic parameters such as white blood cell count, hemoglobin, platelets, calcium, phosphate, albumin, and CRP. Furthermore, we plan to assess the rate of PTH recovery following clinical resolution of infection and explore its potential association with clinical outcomes, including recurrent infections, cardiovascular morbidity, and mortality.
Research Hypothesis:
- In hemodialysis patients with catheter-related bloodstream infections, blood cultures drawn from the dialysis machine are expected to detect infection as effectively, or possibly more effectively, than peripheral venous blood cultures.
- Changes in parathyroid hormone (PTH) levels may indicate an increased risk of mortality, potentially informing treatment adjustments and monitoring strategies in dialysis patients with acute infections.
Study Objectives:
- To compare the diagnostic yield of blood cultures obtained from three different sources in hemodialysis patients:
- Central venous catheter (CVC),
- Dialysis machine (during treatment),
- Peripheral vein.
- To measure PTH levels during sepsis and compare them to baseline pre-infection levels, with serial follow-up of PTH values post-recovery.
- To assess clinical outcomes including infectious and cardiovascular complications, and mortality, in correlation with PTH levels in patients experiencing sepsis.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hemodialysis patients with suspected catheter-related bloodstream infections (CRBSIs). | – | Diagnostic Test: Blood cultures will be obtained from three sources: 1. The central venous catheter (CVC), 2. The dialysis machine circuit, and 3. A peripheral veinStudy Population: The study will include hemodialysis patients over the age of 18 who are hospitalized at the Galilee Medical Center due to sepsis and have provided written informed consent to participate in this study. Study Procedure: During hospitalization, and as part of the clinical workup for sepsis, blood cultures will be obtained from three sources: 1. The central venous catheter (CVC), 2. The dialysis machine circuit, and 3. A peripheral vein. In addition, parathyroid hormone (PTH) levels will be measured through a blood sample. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Hemodialysis patients over the age of 18 who are hospitalized at the Galilee Medical Center due to sepsis and have provided written informed consent to participate in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood cultures will be obtained from three sources: 1. The central venous catheter (CVC), 2. The dialysis machine circuit, and 3. A peripheral veinPTH levels during sepsis and compare them to baseline pre-infection levels, with serial follow-up of PTH values post-recovery. | Diagnostic test | Hemodialysis patients with suspected catheter-related bloodstream infections (CRBSIs). |
Primary outcome
Rate of Positive Blood Cultures by Sampling Site Among Documented Bloodstream Infections (CVC, Dialysis Machine, Peripheral Vein)
Time frame: Within 21 days of hospitalization
This outcome measure will compare the proportion of positive blood cultures obtained from three different sampling sites-central venous catheter (CVC), dialysis machine, and peripheral vein-among all confirmed cases of bloodstream infection in dialysis patients. The goal is to evaluate the diagnostic yield of each site and identify the most sensitive and reliable source for detecting bloodstream infections. Findings will support evidence-based recommendations regarding the preferred site for blood culture collection in this population. Comparative analysis will include statistical evaluation of sensitivity, yield, and agreement between sites.
Change in Parathyroid Hormone (PTH) Levels During Infection and Rate of PTH Recovery Post-Discharge
Time frame: 90 days post-discharge
This outcome measure will evaluate the change in parathyroid hormone (PTH) levels during acute infection and the monthly rate of recovery after hospital discharge in dialysis patients. PTH levels will be measured at three time points: (1) during the acute infection, (2) at discharge, and (3) monthly for up to 90 days post-discharge. The primary analysis will assess the magnitude of PTH suppression during infection and the trajectory of recovery over time. These parameters will be analyzed for their correlation with key 90-day outcomes, including infectious complications, cardiovascular events, and all-cause mortality. Statistical analyses will include repeated measures ANOVA and mixed-effects models to evaluate longitudinal changes and their association with clinical endpoints.
3 secondary outcomes
Rate of Recurrent Infections Within 90 Days of Hospital Discharge
Time frame: 90 days post-discharge
Incidence of Cardiovascular Events Within 90 Days of Hospital Discharge
Time frame: 90 days post-discharge
All-Cause Mortality Within 180 Days of Hospital Discharge.
Time frame: 180 days post-discharge
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Results publication: PubMed 20199875Dukkipati R, Kovesdy CP, Colman S, Budoff MJ, Nissenson AR, Sprague SM, Kopple JD, Kalantar-Zadeh K. Association of relatively low serum parathyroid hormone with malnutrition-inflammation complex and survival in maintenance hemodialysis patients. J Ren Nutr. 2010 Jul;20(4):243-54. doi: 10.1053/j.jrn.2009.10.006. Epub 2010 Mar 3.
- Results publication: PubMed 12270308Ozdemir FN, Yakupoglu U, Turan M, Arat Z, Karakayali H, Erdal R, Turan M. Role of parathormone levels on T-cell response in hemodialysis patients. Transplant Proc. 2002 Sep;34(6):2044-5. doi: 10.1016/s0041-1345(02)02846-4. No abstract available.
- Results publication: PubMed 18348986Canaff L, Zhou X, Hendy GN. The proinflammatory cytokine, interleukin-6, up-regulates calcium-sensing receptor gene transcription via Stat1/3 and Sp1/3. J Biol Chem. 2008 May 16;283(20):13586-600. doi: 10.1074/jbc.M708087200. Epub 2008 Mar 17.
- Results publication: PubMed 26612442Hendy GN, Canaff L. Calcium-sensing receptor, proinflammatory cytokines and calcium homeostasis. Semin Cell Dev Biol. 2016 Jan;49:37-43. doi: 10.1016/j.semcdb.2015.11.006. Epub 2015 Nov 21.
- Results publication: PubMed 31648433Hong YA, Kim JH, Kim YK, Chang YK, Park CW, Kim SY, Kim YS, Kang SW, Kim NH, Kim YL, Yang CW. Low parathyroid hormone level predicts infection-related mortality in incident dialysis patients: a prospective cohort study. Korean J Intern Med. 2020 Jan;35(1):160-170. doi: 10.3904/kjim.2018.264. Epub 2019 Oct 28.
- Results publication: PubMed 27037271Quittnat Pelletier F, Joarder M, Poutanen SM, Lok CE. Evaluating Approaches for the Diagnosis of Hemodialysis Catheter-Related Bloodstream Infections. Clin J Am Soc Nephrol. 2016 May 6;11(5):847-854. doi: 10.2215/CJN.09110815. Epub 2016 Apr 1.
- Results publication: PubMed 21467014O'Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, Lipsett PA, Masur H, Mermel LA, Pearson ML, Raad II, Randolph AG, Rupp ME, Saint S; Healthcare Infection Control Practices Advisory Committee (HICPAC) (Appendix 1). Summary of recommendations: Guidelines for the Prevention of Intravascular Catheter-related Infections. Clin Infect Dis. 2011 May;52(9):1087-99. doi: 10.1093/cid/cir138. No abstract available.
- Results publication: PubMed 38536779Guo H, Zhang L, He H, Wang L. Risk factors for catheter-associated bloodstream infection in hemodialysis patients: A meta-analysis. PLoS One. 2024 Mar 27;19(3):e0299715. doi: 10.1371/journal.pone.0299715. eCollection 2024.
- Results publication: PubMed 31151433Delistefani F, Wallbach M, Muller GA, Koziolek MJ, Grupp C. Risk factors for catheter-related infections in patients receiving permanent dialysis catheter. BMC Nephrol. 2019 May 31;20(1):199. doi: 10.1186/s12882-019-1392-0.
- Results publication: PubMed 9596085Hoen B, Paul-Dauphin A, Hestin D, Kessler M. EPIBACDIAL: a multicenter prospective study of risk factors for bacteremia in chronic hemodialysis patients. J Am Soc Nephrol. 1998 May;9(5):869-76. doi: 10.1681/ASN.V95869.
- Results publication: PubMed 24651074Murea M, James KM, Russell GB, Byrum GV 3rd, Yates JE, Tuttle NS, Bleyer AJ, Burkart JM, Freedman BI. Risk of catheter-related bloodstream infection in elderly patients on hemodialysis. Clin J Am Soc Nephrol. 2014 Apr;9(4):764-70. doi: 10.2215/CJN.07710713. Epub 2014 Mar 20.
- Results publication: PubMed 32550235Martin K, Lorenzo YSP, Leung PYM, Chung S, O'flaherty E, Barker N, Ierino F. Clinical Outcomes and Risk Factors for Tunneled Hemodialysis Catheter-Related Bloodstream Infections. Open Forum Infect Dis. 2020 Apr 11;7(6):ofaa117. doi: 10.1093/ofid/ofaa117. eCollection 2020 Jun.
- Individual participant dataSharing planned: Yes. The following individual participant data (IPD) will be shared: Demographic information (age, sex, dialysis vintage) Clinical data relevant to the study (reason for hospitalization, comorbidities, dialysis modality) Blood culture results from all sampling sites (central catheter, dialysis machine, peripheral vein) Laboratory values, including PTH levels at baseline and during infection Outcome data, including complications during hospitalization, cardiovascular events, and 90-day mortality All shared data will be de-identified to protect patient confidentiality, in compliance with relevant privacy regulations and ethical guidelines.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Hemodialysis, run by Western Galilee Hospital-Nahariya at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Etty Kruzel-Davila, MD (972-4-9107619, ETTYK@gmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Positive Blood Cultures by Sampling Site Among Documented Bloodstream Infections (CVC, Dialysis Machine, Peripheral Vein) (time frame: Within 21 days of hospitalization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06963853, which also lists 24 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.