Septic ShockPhase 3NCT03302650
Angiotensin II for Septic Shock Treatment
A Phase 3 study testing Angiotensin II, Normal saline and Norepinephrine in people with Septic Shock, run by Cairo University at 1 site in Egypt.
Trial summary
This study aims to investigate the effect of angiotensin II on microcirculation and peripheral perfusion in patients with septic shock. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Septic Shock
- What is being tested?
- Angiotensin II, Normal saline and Norepinephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Apr 2019to 15 Aug 2019
- Phase
- Phase 3
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Septic shock patients.
- Aged above 18 years.
- With cardiac index > 2.4 L/min/BSA 1.73 m2.
- On high dose vasopressors (defined as norepinephrine infusion above 0.1 mcg/Kg/min)
Who cannot join
- Acute coronary syndrome.
- Impaired cardiac contractility
- Bronchospasm.
- Major burns
- Liver failure.
- Active bleeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Angiotensin II for Septic Shock Treatment: Effects On Macro- and Microcirculation A Randomized, Controlled Pilot Trial (ANGSTROM Trial)
This study aims to investigate the effect of angiotensin II on microcirculation and peripheral perfusion in patients with septic shock.
Read the detailed description
Shock is a syndrome characterized by acute circulatory failure resulting in impaired peripheral tissue perfusion. Distributive shock is the most common type of shock and is usually caused by severe sepsis. Distributive shock is characterized by profound vasodilatation leading to decreased arterial blood pressure and impaired organ perfusion despite high cardiac output.
The use of vasopressors is an essential management line for distributive sock. Two groups of vasopressors are usually used for management of shock: catecholamines and vasopressin-like peptides. There is a continuous need for other vasopressors because:
1- Available vasopressors have narrow therapeutic window. 2- Patients with severe hypotension refractory to the currently available classes usually die.
A third system is usually engaged in the physiology of shock which is Renin-Angiotensin-aldosterone system. Angiotensin II is a natural hormone which is a potent vasopressor; moreover, angiotensin II stimulates the production of both antidiuretic hormone and adrenocorticotropin hormone.
In a pilot study, angiotensin II was reported as an effective rescue vasopressor in septic shock patients on multiple vasopressors. Angiotensin II improved mean arterial pressure and helped in reduction of the doses of catecholamines. In a recent large randomized controlled trial, angiotensin II improved blood pressure in catecholamine-resistant distributive shock patients.
Microcirculation is the primary site of oxygen and nutrient exchange. Maintenance of microcirculatory perfusion is a prerequisite for preservation of organ function. Multiple organ failure is common in patients with distributive shock despite maintenance of parameters of global perfusion due to disrupted microcirculatory perfusion. Furthermore, restoration of microcirculatory perfusion was correlated with improvement in survival. This study aims to investigate the effect of angiotensin II on peripheral microcirculation in patients with septic shock.
- Conditions
- Septic Shock
- Being tested
- Angiotensin II, Normal saline, Norepinephrine
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin IIDrug
Patients will receive angiotensin-II at a starting dose of 20 ng/Kg/min.
Normal salineDrug
Patients will receive normal saline.
NorepinephrineDrug
Also called Noradrenaline
patients will receive norepinephrine infusion adjusted according to blood pressure
| Study group | Role | What they receive |
|---|---|---|
| Angiotensin group | Experimental | Patients will receive Angiotensin II at a starting dose of 20 ng/Kg/min. During the first 30 minutes after randomization, the angiotensin II infusion will be titrated to achieve a mean arterial pressure of 65-75 mmHg while the norepinephrine infusion will be withdrawn and stopped. Following a stabilization of 60 minutes, the angiotensin II infusion is titrated to achieve a mean arterial pressure of 85-95 mmHg. Following a 30 minutes wash-in period and a 60 minutes stabilization period, a third set of measurements will be taken. Then, the angiotensin II infusion will be withdrawn in small steps and replaced by a norepinephrine infusion which will then be titrated to achieve a mean arterial pressure of 65-75 mmHg. Then, the final set of measurements will be taken. Receives: Drug: Angiotensin II; Drug: Norepinephrine |
| Normal saline group | Placebo comparator | Patients will receive normal saline infusion in addition to norepinephrine infusion. The same mean arterial pressure levels (65-75 mmHg > 85-95 mmHg > 65-75 mmHg) will be achieved by titration of the norepinephrine infusion. Identical wash-in and stabilization periods will be kept as in the study group. Measurements will be taken at the same time points as in the study group. The maximum dose of norepinephrine applied will be 0.7 mcg/kg/min. Receives: Drug: Normal saline; Drug: Norepinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean flow index
Mean flow index measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands).
The microvascular flow index (MFI) will be used to quantify microvascular blood flow. In this score, flow is characterized as absent (0), intermittent (1), sluggish (2), or normal (3), for each patient the values from 5 videos will be averaged. Since our investigation will be focused on small vessels, calculations will be separately performed for vessels with a diameter less than 20 ųm.
Measured: 6 Hours
Secondary outcomes (15)
Proportion of perfused vessels
Proportion of perfused vessels measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands)
Measured: 6 Hours
Perfused vessel density
Perfused vessel density measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands)
Measured: 6 Hours
systolic blood pressure
systolic blood pressure measured in mmHg
Measured: 6 hours
Diastolic blood pressure
diastolic blood pressure measured in mmHg
Measured: 6 hours
Heart rate
heart rate in beats per minute
Measured: 6 hours
Serum lactate
Serum lactate measured in milligrams per deciliter
Measured: 6 hours
Urine output
quantity of urine in milliliters
Measured: 6 hours
Serum Creatinine
serum creatinine measured in milligrams per deciliter
Measured: 24 hours
Serum Sodium
Serum sodium measured in milligrams per deciliter
Measured: 24 hours
Serum potassium
Serum potassium measured in milligrams per deciliter
Measured: 24 hours
Cardiac output
quantity of blood pumper by the heart measured by electrical cardiometry in liters per minute
Measured: 6 hours
systemic vascular resistance
systemic vascular resistance measured by electrical cardiometry
Measured: 6 hours
Norepinephrine requirements
total requirement of norepinephrine needed to maintain mean arterial blood pressure above 65 mmHg
Measured: 6 hours
perfusion index
proportion of pulsatile to non-pulsatile portions in peripheral circulation
Measured: 6 hours
total fluid intake
amount of fluids received by the patient in milliliters
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2017
- Study start1 Apr 2019 (estimated)
- Primary completion1 Aug 2019 (estimated)
- Study completion15 Aug 2019 (estimated)
Why it stopped: The drug is not available
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmed Hasanin, Cairo University
- Investigators
- Ahmed Mukhtar, Professor, Study director, Head of research committee section in anesthesia departmentMartin W Dünser, Professor, Study director, Department of critical care, University of London college hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03302650
- Sponsor's protocol ID
- N-68-2017
- Status last verified
- Jan 2019
- First submitted
- 1 Oct 2017
- Last updated
- 16 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angiotensin II for Septic Shock Treatment: Effects On Macro- and Microcirculation A Randomized, Controlled Pilot Trial (ANGSTROM Trial)
- ClinicalTrials.gov ID
- NCT03302650
- Acronym / sponsor ID
- N-68-2017
- Conditions
- Septic Shock
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: The drug is not available
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 1 Apr 2019 (estimated)
- Primary completion
- 1 Aug 2019 (estimated)
- Study completion
- 15 Aug 2019 (estimated)
- First posted
- 5 Oct 2017 (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 study aims to investigate the effect of angiotensin II on microcirculation and peripheral perfusion in patients with septic shock.
Detailed description
Shock is a syndrome characterized by acute circulatory failure resulting in impaired peripheral tissue perfusion. Distributive shock is the most common type of shock and is usually caused by severe sepsis. Distributive shock is characterized by profound vasodilatation leading to decreased arterial blood pressure and impaired organ perfusion despite high cardiac output.
The use of vasopressors is an essential management line for distributive sock. Two groups of vasopressors are usually used for management of shock: catecholamines and vasopressin-like peptides. There is a continuous need for other vasopressors because:
1- Available vasopressors have narrow therapeutic window. 2- Patients with severe hypotension refractory to the currently available classes usually die.
A third system is usually engaged in the physiology of shock which is Renin-Angiotensin-aldosterone system. Angiotensin II is a natural hormone which is a potent vasopressor; moreover, angiotensin II stimulates the production of both antidiuretic hormone and adrenocorticotropin hormone.
In a pilot study, angiotensin II was reported as an effective rescue vasopressor in septic shock patients on multiple vasopressors. Angiotensin II improved mean arterial pressure and helped in reduction of the doses of catecholamines. In a recent large randomized controlled trial, angiotensin II improved blood pressure in catecholamine-resistant distributive shock patients.
Microcirculation is the primary site of oxygen and nutrient exchange. Maintenance of microcirculatory perfusion is a prerequisite for preservation of organ function. Multiple organ failure is common in patients with distributive shock despite maintenance of parameters of global perfusion due to disrupted microcirculatory perfusion. Furthermore, restoration of microcirculatory perfusion was correlated with improvement in survival. This study aims to investigate the effect of angiotensin II on peripheral microcirculation in patients with septic shock.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Angiotensin group | Experimental | Drug: Angiotensin II, Drug: NorepinephrinePatients will receive Angiotensin II at a starting dose of 20 ng/Kg/min. During the first 30 minutes after randomization, the angiotensin II infusion will be titrated to achieve a mean arterial pressure of 65-75 mmHg while the norepinephrine infusion will be withdrawn and stopped. Following a stabilization of 60 minutes, the angiotensin II infusion is titrated to achieve a mean arterial pressure of 85-95 mmHg. Following a 30 minutes wash-in period and a 60 minutes stabilization period, a third set of measurements will be taken. Then, the angiotensin II infusion will be withdrawn in small steps and replaced by a norepinephrine infusion which will then be titrated to achieve a mean arterial pressure of 65-75 mmHg. Then, the final set of measurements will be taken. |
| Normal saline group | Placebo comparator | Drug: Normal saline, Drug: NorepinephrinePatients will receive normal saline infusion in addition to norepinephrine infusion. The same mean arterial pressure levels (65-75 mmHg > 85-95 mmHg > 65-75 mmHg) will be achieved by titration of the norepinephrine infusion. Identical wash-in and stabilization periods will be kept as in the study group. Measurements will be taken at the same time points as in the study group. The maximum dose of norepinephrine applied will be 0.7 mcg/kg/min. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Septic shock patients.
- Aged above 18 years.
- With cardiac index > 2.4 L/min/BSA 1.73 m2.
- On high dose vasopressors (defined as norepinephrine infusion above 0.1 mcg/Kg/min)
Key exclusion criteria (6 listed)
- Acute coronary syndrome.
- Impaired cardiac contractility
- Bronchospasm.
- Major burns
- Liver failure.
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 |
|---|---|---|
| Angiotensin IIPatients will receive angiotensin-II at a starting dose of 20 ng/Kg/min. | Drug | Angiotensin group |
| Normal salinePatients will receive normal saline. | Drug | Normal saline group |
| NorepinephrineAlso: Noradrenalinepatients will receive norepinephrine infusion adjusted according to blood pressure | Drug | Angiotensin group, Normal saline group |
Primary outcome
Mean flow index
Time frame: 6 Hours
Mean flow index measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands). The microvascular flow index (MFI) will be used to quantify microvascular blood flow. In this score, flow is characterized as absent (0), intermittent (1), sluggish (2), or normal (3), for each patient the values from 5 videos will be averaged. Since our investigation will be focused on small vessels, calculations will be separately performed for vessels with a diameter less than 20 ųm.
15 secondary outcomes
Proportion of perfused vessels
Time frame: 6 Hours
Perfused vessel density
Time frame: 6 Hours
systolic blood pressure
Time frame: 6 hours
Diastolic blood pressure
Time frame: 6 hours
Heart rate
Time frame: 6 hours
Serum lactate
Time frame: 6 hours
Urine output
Time frame: 6 hours
Serum Creatinine
Time frame: 24 hours
Serum Sodium
Time frame: 24 hours
Serum potassium
Time frame: 24 hours
Cardiac output
Time frame: 6 hours
systemic vascular resistance
Time frame: 6 hours
Norepinephrine requirements
Time frame: 6 hours
perfusion index
Time frame: 6 hours
total fluid intake
Time frame: 24 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2019.
- Individual participant dataSharing planned: Undecided
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Septic Shock
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.
Ahmed Mukhtar, Professor study director
Head of research committee section in anesthesia department
Martin W Dünser, Professor study director
Department of critical care, University of London college hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Angiotensin II, Normal saline and Norepinephrine in people with Septic Shock, run by Cairo University at 1 site in Egypt.
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 4 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: paused, as of the sponsor's last update on 16 Jan 2019. 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 Egypt. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Mean flow index (time frame: 6 Hours). 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 16 Jan 2019.