SepsisERASPPWSNCT03952390
Effect of Renin-Angiotensin System on Platelet in Patient With Sepsis
An observational study of Sepsis, run by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Sepsis
- What is being tested?
- sepsis
- How many people
- 53 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2018to 15 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
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 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: patients with sepsis
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Anesthesia, Shanghai Xinhua hospital
Shanghai, Shanghai Municipality, 200082
About this study
Official title: Study on the Effect of Renin-Angiotensin System on Thrombocytopenia in Patient With Sepsis
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.
Read the 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.
- Conditions
- Sepsis
- Being tested
- control, sepsis
- Keywords
- thrombocytopenia,Renin-Angiotensin System,platelet
- Medical subject headings
- Sepsis, Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
controlOther
Also called healthy volunteers
sepsisOther
Also called patients with sepsis
| Study group | Role | What they receive |
|---|---|---|
| control | healthy volunteers Receives: Other: control | |
| sepsis | patients with sepsis Receives: Other: sepsis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet Count of Blood Sample
The platelet count of venous blood samples collected from patients with sepsis was measured by Blood routine instrument,Beckman CoulterLH750.
Measured: 20-60min
The Plasma Renin Activity of Blood Sample
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.
Measured: 20-60min
The Plasma Concentration of AngiotensinⅡ in Blood Sample
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.
Measured: 20-60min
Secondary outcomes (2)
Correlation Coefficient (r) Between Platelet Count and The Plasma Renin Activity
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.
Measured: 20-60min
Correlation Coefficient (r) Between Platelet Count and The Plasma Concentration of AngiotensinⅡ
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.
Measured: 20-60min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2019
- Study start1 Jan 2018
- Primary completion10 Dec 2019
- Study completion15 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Xinhua Hospital, Shanghai Jiao Tong University School of MedicineThe sponsor's other registered studies.
- 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-control
- Time perspective
- Prospective
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lai Jiang, chief doctor, Study chair, Xinhua Hospital affiliated to Medicine school,Shanghai Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03952390
- Sponsor's protocol ID
- XHEC-C-2017-080
- Acronym
- ERASPPWS
- Status last verified
- Dec 2018
- First submitted
- 15 Jan 2019
- Last updated
- 18 Jan 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on the Effect of Renin-Angiotensin System on Thrombocytopenia in Patient With Sepsis
- ClinicalTrials.gov ID
- NCT03952390
- Acronym / sponsor ID
- ERASPPWS / XHEC-C-2017-080
- Conditions
- Sepsis
- Keywords
- thrombocytopenia,Renin-Angiotensin System,platelet
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Xinhua Hospital, Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 10 Dec 2019 (actual)
- Study completion
- 15 Dec 2019 (actual)
- First posted
- 16 May 2019 (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.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| control | – | Other: controlhealthy volunteers |
| sepsis | – | Other: sepsispatients with sepsis |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- patients with sepsis
Key inclusion criteria (9 listed)
- Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to 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.
- Abbreviations: MAP, mean arterial pressure; qSOFA, quick SOFA; SOFA: Sequential[Sepsis-related] Organ Failure Assessment.
Key exclusion criteria (6 listed)
- 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.
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 |
|---|---|---|
| controlAlso: healthy volunteers | Other | control |
| sepsisAlso: patients with sepsis | Other | sepsis |
Primary outcome
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.
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.
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.
2 secondary outcomes
Correlation Coefficient (r) Between Platelet Count and The Plasma Renin Activity
Time frame: 20-60min
Correlation Coefficient (r) Between Platelet Count and The Plasma Concentration of AngiotensinⅡ
Time frame: 20-60min
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
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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. This study is not recruiting at the moment.
Lai Jiang, chief doctor study chair
Xinhua Hospital affiliated to Medicine school,Shanghai Jiaotong University
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, run by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. 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: finished, as of the sponsor's last update on 18 Jan 2020. 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 China. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Platelet Count of Blood Sample (time frame: 20-60min). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jan 2020.