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Effect of Renin-Angiotensin System on Platelet in Patient With Sepsis (ERASPPWS)

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ClinicalTrials.gov Identifier: NCT03952390
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Brief Summary:
As a common and serious medical condition , sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection , which is a major and familiar cause of death in intensive care units(ICU). As a frequent laboratory abnormality in patients with sepsis , thrombocytopenia on intensive care unit admission is independently associated with increased mortality in patients. Furthermore, a low platelet count is a marker with further significance , which is always used for evaluating the prognosis of patients. Herein, this study aimed to investigate the effect of renin-angiotensin system on thrombocytopenia in patient with sepsis and explore the possible underlying molecular mechanisms.

Condition or disease Intervention/treatment
Sepsis Other: control Other: sepsis

Detailed Description:

Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. According to the Centers for Disease Control and Prevention, sepsis occurs in 1.5 million Americans annually and it causes more than 250,000 deaths annually in the United States alone. Thrombocytopenia is a frequent laboratory abnormality in patients with sepsis. Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more represents organ dysfunction . As the index of coagulation , platelet count is involved in SOFA . The changes of quality and quantity in platelet is closely associated with the morbidity and mortality of infectious diseases . Furthermore , thrombocytopenia is independently related with increased mortality in severe sepsis patients . Therefore , rectify of thrombocytopenia is of significant role to prevent potentially life-threatening complications in patients with sepsis. Currently , donor-derived platelet transfusion is the only treatment of severe thrombocytopenia seen in sepsis . However , platelets used in the clinic is associated with lots of concerns , for example , sufficient availability , quality , and complications due to immunologic and/or infectious issues . So , it is necessary and urgent to focus our efforts on the development of therapeutic agents to overcome our dependence on donor-derived platelets for transfusion .

Deriving from megakaryocytes , platelets are anucleate , having only cytoplasmic components imparted by megakaryocytes residing in the bone marrow,circulating in the bloodstream and having an important role in the body because of their functions in hemostasis , thrombosis , inflammation , and vascular biology . There are numerous reasons why thrombocytopenia often accompany patients with sepsis , such as platelet-vessel wall interaction , excessive consumption of platelet in DIC and platelet activation . Furthermore, research indicates that the intrinsic machinery for programmed cell death (apoptosis) regulates the life span of the anucleate platelet. Besides, several mechanisms have been proposed to explain the platelet apoptosis ,among which reactive oxygen sepsis(ROS) appears to play critical role.

More studies have shown that the renin-angiotensin-aldosterone system(RAAS) is activated in sepsis,providing an important physiologic mechanism to preserve volume status and vascular tone. As the main effect factor of the RAAS, angiotensin II plays a key role in several biological processes, including apoptosis,coagulation ,cell growth, and inflammatory response in addition to its classical hemodynamic function of regulating arterial blood pressure.Numerous researches claimed , angiotensin II (Ang II) has been associated with organ failures and mortality by promoting the generation of a large amount of intracellular ROS. However, no studies have shown the relation between Ang II-related ROS and thrombocytopenia during sepsis.

Therefore, the investigators hypothesized that Ang II , by promoting the generation of a large amount of intracellular ROS , plays a critical role in the development of thrombocytopenia during sepsis.In the present study, the investigators will analyze the mechanism of platelet apoptosis during sepsis, and explore whether angiotensin II receptor blockers could protect ROS induced platelet apoptosis, which is helpful for prevention and treatment of thrombocytopenia.


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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Study on the Effect of Renin-Angiotensin System on Thrombocytopenia in Patient With Sepsis
Actual Study Start Date : January 1, 2018
Estimated Primary Completion Date : December 10, 2019
Estimated Study Completion Date : December 15, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Group/Cohort Intervention/treatment
control
healthy volunteers
Other: control
Other Name: healthy volunteers

sepsis
patients with sepsis
Other: sepsis
Other Name: patients with sepsis




Primary Outcome Measures :
  1. Platelet Count of Blood Sample [ Time Frame: 20-60min ]
    The platelet count of venous blood samples collected from patients with sepsis was measured by Blood routine instrument,Beckman CoulterLH750.

  2. The Plasma Renin Activity of Blood Sample [ Time Frame: 20-60min ]
    Venous blood samples were collected in ethylenediaminetetraacetic acid (EDTA),dimercaptopropanol and 8 - hydroxyquinoline sulfate plus blood collection tubes, followed by centrifugation to separate plasma from venous blood samples.The plasma renin activity of venous blood samples collected from patients with sepsis was measured by Iodine[125I]AngiotensinⅡRadioimmunoassay Kit.

  3. The Plasma Concentration of AngiotensinⅡ in Blood Sample [ Time Frame: 20-60min ]
    Venous blood samples were collected in ethylenediaminetetraacetic acid (EDTA) ,dimercaptopropanol and 8 - hydroxyquinoline sulfate plus blood collection tubes, followed by centrifugation to separate plasma from venous blood samples.The plasma concentration of angiotensinⅡ in venous blood samples collected from patients with sepsis was measured by Iodine[125I]AngiotensinⅡRadioimmunoassay Kit.


Secondary Outcome Measures :
  1. Correlation Coefficient (r) Between Platelet Count and The Plasma Renin Activity [ Time Frame: 20-60min ]
    GraphPad Prism5 software were used to analysis the correlation coefficient (r) between platelet count and the plasma renin activity.If p value is less than 0.05, then its change is statically significant.

  2. Correlation Coefficient (r) Between Platelet Count and The Plasma Concentration of AngiotensinⅡ [ Time Frame: 20-60min ]
    GraphPad Prism5 software were used to analysis the correlation coefficient (r) between platelet count and the plasma concentration of angiotensinⅡ.If p value is less than 0.05, then its change is statically significant.


Biospecimen Retention:   Samples Without DNA
plasma seperated from venous blood via centrifugation


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
patients with sepsis
Criteria

Inclusion Criteria:

  • Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.

    • Organ dysfunction can be identified as an acute change in total SOFA score ≥2 points consequent to the infection.

  • The baseline SOFA score can be assumed to be zero in patients not known to have preexisting organ dysfunction.
  • ASOFA score ≥2 reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection. Even patients presenting with modest dysfunction can deteriorate further,emphasizing the seriousness of this condition and the need for prompt and appropriate intervention, if not already being instituted.

    • In lay terms, sepsis is a life-threatening condition that arises when the body's response to an infection injures its own tissues and organs.
    • Patients with suspected infection who are likely to have a prolonged ICU stay or to die in the hospital can be promptly identified at the bedside with qSOFA, ie, alteration in mental status, systolic blood pressure ≥100 mm Hg, or respiratory rate ≥22/min.
    • Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.
    • Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L (18mg/dL) despite adequate volume resuscitation. With these criteria,hospital mortality is in excess of 40%.

Abbreviations: MAP, mean arterial pressure; qSOFA, quick SOFA; SOFA: Sequential[Sepsis-related] Organ Failure Assessment.

Exclusion Criteria:

  • Pregnant or lactation period.
  • Age <18 years or >85 years.
  • Receiving chemotherapy, steroid or immunosuppressive agents recently.
  • Receiving any drugs that affect Renin-Angiotensin-System(RAS),sunch as Angiotensin Converting Enzyme Inhibitor(ACEI),Angiotensin Receptor Blockers(ARB),diuretics,calcium channel blockers and other antihypertensives within two weeks .
  • Receiving oral contraceptives within twelve weeks.
  • Enrollment before resuscitation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03952390


Contacts
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Contact: Lai Jiang, chief doctor +86-021-25077821 jianglaimz@sina.com
Contact: Dunfeng Xu, resident 18917095817@163.com

Locations
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China, Shanghai
Department of Anesthesia, Shanghai Xinhua hospital Recruiting
Shanghai, Shanghai, China, 200082
Contact: Lai Jiang, chief doctor    +86-021-25077821    jianglaimz@163.com   
Sponsors and Collaborators
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Investigators
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Study Chair: Lai Jiang, chief doctor Xinhua Hospital affiliated to Medicine school,Shanghai Jiaotong University

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Responsible Party: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier: NCT03952390     History of Changes
Other Study ID Numbers: XHEC-C-2017-080
First Posted: May 16, 2019    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine:
thrombocytopenia,Renin-Angiotensin System,platelet

Additional relevant MeSH terms:
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Sepsis
Toxemia
Thrombocytopenia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Blood Platelet Disorders
Hematologic Diseases