- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03952390
Effect of Renin-Angiotensin System on Platelet in Patient With Sepsis (ERASPPWS)
Study on the Effect of Renin-Angiotensin System on Thrombocytopenia in Patient With Sepsis
Study Overview
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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Shanghai
-
Shanghai, Shanghai, China, 200082
- Department of Anesthesia, Shanghai Xinhua hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
control
healthy volunteers
|
Other Names:
|
sepsis
patients with sepsis
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
20-60min
|
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.
|
20-60min
|
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.
|
20-60min
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
20-60min
|
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.
|
20-60min
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- XHEC-C-2017-080
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Sepsis
-
University of Kansas Medical CenterUniversity of KansasRecruitingSepsis | Septic Shock | Sepsis Syndrome | Sepsis, Severe | Sepsis Bacterial | Sepsis BacteremiaUnited States
-
Jip GroenInBiomeRecruitingMicrobial Colonization | Neonatal Infection | Neonatal Sepsis, Early-Onset | Microbial Disease | Clinical Sepsis | Culture Negative Neonatal Sepsis | Neonatal Sepsis, Late-Onset | Culture Positive Neonatal SepsisNetherlands
-
Karolinska InstitutetÖrebro University, SwedenCompletedSepsis | Sepsis Syndrome | Sepsis, SevereSweden
-
The University of QueenslandRoyal Brisbane and Women's HospitalUnknown
-
Indonesia UniversityCompletedSevere Sepsis With Septic Shock | Severe Sepsis Without Septic ShockIndonesia
-
Ohio State UniversityCompletedSepsis, Severe Sepsis and Septic ShockUnited States
-
Beckman Coulter, Inc.Biomedical Advanced Research and Development AuthorityRecruitingSevere Sepsis | Severe Sepsis Without Septic ShockUnited States
-
University of LeicesterUniversity Hospitals, Leicester; The Royal College of AnaesthetistsCompletedSepsis | Septic Shock | Severe Sepsis | Sepsis SyndromeUnited Kingdom
-
Zagazig UniversityRecruitingSepsis-associated EncephalopathyEgypt
-
Weill Medical College of Cornell UniversityNational Heart, Lung, and Blood Institute (NHLBI); New York Presbyterian Hospital and other collaboratorsCompletedSepsis | Septic Shock | Severe Sepsis | Infection | Sepsis SyndromeUnited States
Clinical Trials on control
-
Claudia M. WittCompleted
-
University of California, San FranciscoWithdrawn
-
The George InstituteChanghai Hospital; University of CalgaryNot yet recruiting
-
Universidad Nacional de Educación a DistanciaMinisterio de Economía y Competitividad, SpainUnknownChronic Pain | FibromyalgiaSpain
-
University of California, Los AngelesThe National Council on Aging; City of Los Angeles Department of Aging; Los Angeles...Completed
-
Queen's University, BelfastPublic Health Agency, Health and Social Care Research and Development; Tiny...Completed
-
National Taiwan University HospitalEnrolling by invitationCognitive Function | Atrial Fibrillation, PersistentTaiwan
-
Takeshi MorimotoUniversity of the RyukyusActive, not recruitingCoronary Artery Disease | Hypertension | Type 2 Diabetes | DyslipidemiaJapan
-
Johnson & Johnson Vision Care, Inc.TerminatedRefractive Error CorrectionUnited States
-
Vanderbilt University Medical CenterCompleted