Sepsis, SeverePhase 4EA-NE-TUNNCT05836272
Early Administration of Norepinephrine in Sepsis
A Phase 4 study testing Norepinephrine Bitartrate in people with Sepsis, Severe, run by Tunis University at 1 site in Tunisia.
Trial summary
The management of septic states includes, in addition to the specific treatment (antimicrobials and eradication of the source), a restoration of the hemodynamic disorders and assistance of the failing organs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Severe
- What is being tested?
- Norepinephrine Bitartrate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteTunisia
- Study dates
- 1 Aug 2023to Aug 2025
- Phase
- Phase 4
- 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
Who may be able to join
- Age 18 or older.
- The patient or his/her legal representative has given informed consent in writing.
- Diagnosis of sepsis according to the definitions updated by the consensus of sepsis 3.
- Mean arterial pressure < 65 mmHg
Who cannot join
- Diagnosis of septic shock prior to randomization (where NA requirements exceed those of the trial protocol)
- Pregnancy,
- Need for immediate surgery,
- Neoplasia at an advanced stage
- Circumstances where water restriction is the rule:
- Acute pulmonary edema
- Acute coronary syndrome,
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Tunisia1 site, 1 recruiting
- Recruiting
intensive care unit of the University Hospital Center La Rabta
Tunis, 1007
Ahlem Trifi, +21698692699, ahlem.ahurabta@gmail.com
About this study
Official title: Early Administration of Norepinephrine in Sepsis (Tunisian Multicenter Randomized Trial)
The management of septic states includes, in addition to the specific treatment (antimicrobials and eradication of the source), a restoration of the hemodynamic disorders and assistance of the failing organs. In general, the restoration of hemodynamic disorders begins first with volume expansion, followed by the use of Noepinephrine (NE) when the target mean arterial pressure (MAP) is not reached after optimizing the intravascular volume. Recently, several studies have supported the interest of early NE on MAP, cardiac output and mortality. It is therefore tempting to restrict fluid administration even in the initial phase of hemodynamic management of severe sepsis by starting NE earlier.
Read the detailed description
Sepsis is characterized by systemic inflammation induced by a severe infection resulting in an inappropriate host response against that infection. On the microcirculatory scale, vasoplegia with capillary leakage is distinguished. Management of sepsis includes, in addition to specific treatment which includes antimicrobials and eradication of the source, restoration of hemodynamic disorders and assistance to failing organs. In general, the restoration of hemodynamic disorders begins first with volume expansion, followed by the use of vasopressors (mainly norepinephrine: NE as first-line therapy) when the mean arterial pressure target (MAP: reflecting the perfusion pressure organs) is not reached after optimizing the intravascular volume.
Recently, several studies have supported the benefit of administering NE at the start of resuscitation of sepsis. Indeed, its administration at an earlier phase than usually recommended improved MAP and cardiac output with a favorable effect on mortality. At a median interval of 1.3 hours from ICU admission and exclusive administration of NE, MAP was adequately restored within a relatively short time (30 min) and was associated with a better survival rate than that predicted by the severity scores of similar patients from other series reported in the literature. In the recent Thai "CENSER" trial, shock was controlled in 76% of patients in the early NE group versus 48% (p<0.001). On the other hand, the administration of a large quantity of fluids inevitably increases the risk of fluid overload, which is a frequent complication in septic patients. In front of all these arguments, it is therefore tempting to restrict fluid administration even to the initial phase of the hemodynamic management of sepsis by starting NE earlier.
- Conditions
- Sepsis, Severe
- Being tested
- Norepinephrine Bitartrate, Placebo
- Keywords
- sepsis, septic shock, Norepinephrine, volume expansion, mortality
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Norepinephrine BitartrateDrug
Also called Norepinephrine 0,016 mg/ml
The NE will be prepared as follows: 4 mg mixed with 250 ml of 5% glucose resulting in a final norepinephrine concentration of 0.016 mg/ml. For the control group placebo: 250 ml of 5% glucose will be prepared.
Both drugs will be infused via a peripheral line or a venous catheter. The intravenous infusion rate varies from 8 to 15 ml/hour, adjusted according to body weight to obtain norepinephrine at 0.05 microgram/kg/min (ie 0.128 to 0.24 mg per hour) in continuous infusion.
PlaceboOther
For the control group placebo: 250 ml of 5% glucose will be prepared and will be infused via a peripheral line or a venous catheter. The intravenous infusion rate varies from 8 to 15 ml/hour.
| Study group | Role | What they receive |
|---|---|---|
| Early NE | Active comparator | The early NE arm will receive low-dose NE as soon as hypotension secondary to sepsis is observed in addition to a classic therapeutic regimen that complies with the guidelines of the 2021 Surviving Sepsis Compaign. Sepsis is defined according to the sepsis 3 consensus by a sepsis related organ failure assessment (SrOFA) score greater than 2 following an infection (documented or suspected) Receives: Drug: Norepinephrine Bitartrate |
| Placebo | Placebo comparator | The placebo arm will receive only the classic therapeutic regimen that complies with the guidelines of the 2021 Surviving Sepsis Compaign. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
shock control
shock control is defined by a composite criterion (MAP > 65 mm Hg for 2 consecutive measurements and urinary output > 0.5 ml/kg/h for 2 consecutive hours)
Measured: within 6 hours
Secondary outcomes (3)
Decrease in serum lactate
Decrease in serum lactate > 10% from baseline
Measured: within 6 hours
Volume of fluid
Quantity of intravenous fluid received
Measured: within 48 hours
Mortality
Mortality
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2023
- Study start1 Aug 2023
- Primary completionJun 2025 (estimated)
- Study completionAug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sepsis, SevereStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This involves randomizing 2 independent groups according to a succession of six blocks of random permutations and this will be carried out using a computer-generated tool: the NE group (early noradrenaline group) which will receive NA at start for correction of hypotension and Placebo group (standard treatment group).
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tunis University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahlem Trifi, Tunis University
- Investigators
- Ahlem Trifi, Principal investigator, Hopital La Rabta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05836272
- Sponsor's protocol ID
- Tunisian ICUs association
- Acronym
- EA-NE-TUN
- Status last verified
- Dec 2024
- First submitted
- 18 Apr 2023
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. Am J Respir Crit Care Med. 2019 May 1;199(9):1097-1105. doi: 10.1164/rccm.201806-1034OC.
PubMed 30704260Trifi A, Abdellatif S, Mehdi A, Messaoud L, Seghir E, Mrad N, Ben Khelil J, Ben Ismail K, Merhaben T, Fradj H, Mokline A, Messaadi AA, Khiari H, Garbaa Y, Borsali Falfoul N, Ennouri E, Toumi R, Boussarsar M, Jaoued O, Atrous S, Ghezala HB, Brahmi N, Trabelsi I, Ghadhoune H, Bradaii S, Bahloul M, Ammar R, Kaaniche FM. Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol. PLoS One. 2024 Jul 18;19(7):e0307407. doi: 10.1371/journal.pone.0307407. eCollection 2024.
PubMed 39024364
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Administration of Norepinephrine in Sepsis (Tunisian Multicenter Randomized Trial)
- ClinicalTrials.gov ID
- NCT05836272
- Acronym / sponsor ID
- EA-NE-TUN / Tunisian ICUs association
- Conditions
- Sepsis, Severe
- Keywords
- sepsis, septic shock, Norepinephrine, volume expansion, mortality
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Tunis UniversityUniversity, hospital or other
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Aug 2025 (estimated)
- First posted
- 1 May 2023 (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.
The management of septic states includes, in addition to the specific treatment (antimicrobials and eradication of the source), a restoration of the hemodynamic disorders and assistance of the failing organs. In general, the restoration of hemodynamic disorders begins first with volume expansion, followed by the use of Noepinephrine (NE) when the target mean arterial pressure (MAP) is not reached after optimizing the intravascular volume. Recently, several studies have supported the interest of early NE on MAP, cardiac output and mortality. It is therefore tempting to restrict fluid administration even in the initial phase of hemodynamic management of severe sepsis by starting NE earlier.
Detailed description
Sepsis is characterized by systemic inflammation induced by a severe infection resulting in an inappropriate host response against that infection. On the microcirculatory scale, vasoplegia with capillary leakage is distinguished. Management of sepsis includes, in addition to specific treatment which includes antimicrobials and eradication of the source, restoration of hemodynamic disorders and assistance to failing organs. In general, the restoration of hemodynamic disorders begins first with volume expansion, followed by the use of vasopressors (mainly norepinephrine: NE as first-line therapy) when the mean arterial pressure target (MAP: reflecting the perfusion pressure organs) is not reached after optimizing the intravascular volume.
Recently, several studies have supported the benefit of administering NE at the start of resuscitation of sepsis. Indeed, its administration at an earlier phase than usually recommended improved MAP and cardiac output with a favorable effect on mortality. At a median interval of 1.3 hours from ICU admission and exclusive administration of NE, MAP was adequately restored within a relatively short time (30 min) and was associated with a better survival rate than that predicted by the severity scores of similar patients from other series reported in the literature. In the recent Thai "CENSER" trial, shock was controlled in 76% of patients in the early NE group versus 48% (p<0.001). On the other hand, the administration of a large quantity of fluids inevitably increases the risk of fluid overload, which is a frequent complication in septic patients. In front of all these arguments, it is therefore tempting to restrict fluid administration even to the initial phase of the hemodynamic management of sepsis by starting NE earlier.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This involves randomizing 2 independent groups according to a succession of six blocks of random permutations and this will be carried out using a computer-generated tool: the NE group (early noradrenaline group) which will receive NA at start for correction of hypotension and Placebo group (standard treatment group).
| Arm | Type | Receives |
|---|---|---|
| Early NE | Active comparator | Drug: Norepinephrine BitartrateThe early NE arm will receive low-dose NE as soon as hypotension secondary to sepsis is observed in addition to a classic therapeutic regimen that complies with the guidelines of the 2021 Surviving Sepsis Compaign. Sepsis is defined according to the sepsis 3 consensus by a sepsis related organ failure assessment (SrOFA) score greater than 2 following an infection (documented or suspected) |
| Placebo | Placebo comparator | Other: PlaceboThe placebo arm will receive only the classic therapeutic regimen that complies with the guidelines of the 2021 Surviving Sepsis Compaign. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 or older.
- The patient or his/her legal representative has given informed consent in writing.
- Diagnosis of sepsis according to the definitions updated by the consensus of sepsis 3.
- Mean arterial pressure < 65 mmHg
Key exclusion criteria (7 listed)
- Diagnosis of septic shock prior to randomization (where NA requirements exceed those of the trial protocol)
- Pregnancy,
- Need for immediate surgery,
- Neoplasia at an advanced stage
- Circumstances where water restriction is the rule:
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 |
|---|---|---|
| Norepinephrine BitartrateAlso: Norepinephrine 0,016 mg/mlThe NE will be prepared as follows: 4 mg mixed with 250 ml of 5% glucose resulting in a final norepinephrine concentration of 0.016 mg/ml. For the control group placebo: 250 ml of 5% glucose will be prepared. Both drugs will be infused via a peripheral line or a venous catheter. The intravenous infusion rate varies from 8 to 15 ml/hour, adjusted according to body weight to obtain norepinephrine at 0.05 microgram/kg/min (ie 0.128 to 0.24 mg per hour) in continuous infusion. | Drug | Early NE |
| PlaceboFor the control group placebo: 250 ml of 5% glucose will be prepared and will be infused via a peripheral line or a venous catheter. The intravenous infusion rate varies from 8 to 15 ml/hour. | Other | Placebo |
Primary outcome
shock control
Time frame: within 6 hours
shock control is defined by a composite criterion (MAP > 65 mm Hg for 2 consecutive measurements and urinary output > 0.5 ml/kg/h for 2 consecutive hours)
3 secondary outcomes
Decrease in serum lactate
Time frame: within 6 hours
Volume of fluid
Time frame: within 48 hours
Mortality
Time frame: 28 days
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 4 Dec 2024.
- Background: PubMed 30704260Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. Am J Respir Crit Care Med. 2019 May 1;199(9):1097-1105. doi: 10.1164/rccm.201806-1034OC.
- Derived from this study: PubMed 39024364Trifi A, Abdellatif S, Mehdi A, Messaoud L, Seghir E, Mrad N, Ben Khelil J, Ben Ismail K, Merhaben T, Fradj H, Mokline A, Messaadi AA, Khiari H, Garbaa Y, Borsali Falfoul N, Ennouri E, Toumi R, Boussarsar M, Jaoued O, Atrous S, Ghezala HB, Brahmi N, Trabelsi I, Ghadhoune H, Bradaii S, Bahloul M, Ammar R, Kaaniche FM. Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol. PLoS One. 2024 Jul 18;19(7):e0307407. doi: 10.1371/journal.pone.0307407. eCollection 2024.
- Individual participant dataSharing planned: No
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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.
Ahlem Trifi principal investigator
Hopital La Rabta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Norepinephrine Bitartrate in people with Sepsis, Severe, run by Tunis University at 1 site in Tunisia.
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 7 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: looking for participants now, as of the sponsor's last update on 4 Dec 2024. 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 Tunisia. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Ahlem Trifi (98692699, trifiahlem2@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
shock control (time frame: within 6 hours). 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 NCT05836272, which also lists 2 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 4 Dec 2024.