Septic ShockCENSERNCT01945983
Early Use of Norepinephrine in Septic Shock Resuscitation
A study testing Early norepinephrine in people with Septic Shock and Severe Sepsis, run by Mahidol University at 1 site in Thailand.
Trial summary
Current septic shock guideline recommends fluid resuscitation as the first treatment. Vasopressors, including norepinephrine is recommended to start after achieve adequate fluid therapy. This can cause a certain duration of systemic hypotension before vasopressor is commenced. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Severe Sepsis
- What is being tested?
- Early norepinephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 310 participants
- Where
- 1 siteThailand
- Study dates
- 3 Oct 2013to Aug 2017
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > or = 18 years old
- Diagnosed severe sepsis or septic shock according to survival sepsis campaign 2013
- Mean arterial pressure < 65 mmHg
Who cannot join
- Pregnancy
- Severe underlying condition that unexpected to survive more than 48 hours
- Severe peripheral vascular disease
- Patient who required major surgery within 24 hours
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Comparison Between Early Norepinephrine Use and Standard Treatment During Severe Sepsis and Septic Shock Resuscitation.
Current septic shock guideline recommends fluid resuscitation as the first treatment. Vasopressors, including norepinephrine is recommended to start after achieve adequate fluid therapy. This can cause a certain duration of systemic hypotension before vasopressor is commenced. Initiation of norepinephrine together with fluid therapy soon after diagnosis of septic shock may increase blood pressure quicker than start treatment with intravenous fluid alone. The rapid restoration of perfusion pressure may improve septic shock outcome.
Read the detailed description
We will include severe infection patient who had evidence of organ dysfunction and hypotension and randomize into 2 groups as following:
- Control group. The patient will receive treatment according to septic shock guideline 2013, which start with intravenous fluid replacement until achieve target central venous pressure (CVP) or pulmonary capillary wedge pressure (PCWP) or other fluid responsive test goal. If the patient's mean arterial blood pressure still lower than 65 mmHg, then norepinephrine or dopamine will initiate to rise blood pressure. The patient will receive 5% dextrose water as the placebo of norepinephrine.
- Early norepinephrine group. The patient will receive fluid therapy together with low dose of norepinephrine (0.05 mcg/kg/min). If after titrate intravenous fluid therapy until achieve goal CVP or PCWP or other fluid responsive test, but the mean blood pressure still lower than 65 mmHg, then additional titrate dose of norepinephrine will be given to the patient according to standard septic shock guideline.
- Conditions
- Septic Shock, Severe Sepsis
- Being tested
- Early norepinephrine, Placebo
- Keywords
- Septic shock, Severe sepsis, Norepinephrine
- Medical subject headings
- Shock, Septic, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early norepinephrineDrug
Also called Early vasopressor therapy
Initiation of norepinephrine, a strong vasoconstrictor, at the initiation of septic shock management, together with fluid resuscitation.
PlaceboDrug
Also called 5%D/W infusion as the placebo of norepinephrine.
5% dextrose water intravenous drip in the same rate of calculated norepinephrine for the patient's body weight
| Study group | Role | What they receive |
|---|---|---|
| Early norepinephrine | Active comparator | Norepinephrine 4 mg in 5% dextrose water 250 ml Intravenous infusion rate range from 8 to 15 ml/hour, adjusted according to patient's body weight to achieve norepinephrine 0.05microgram/kg/min Continuous drip for 48 hours. Receives: Drug: Early norepinephrine |
| Placebo | Placebo comparator | 5% dextrose water 250 ml Intravenous infusion rate range from 8 to 15 ml/hour. Adjust rate of infusion according to patient's body weight to achieve dosage of norepinephrine comparable to 0.05 microgram/kg/min Continuous drip for 48 hours. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Therapeutic goal achievement
Therapeutic goal including
- Mean arterial blood pressure > or = 65 mmHg
- Evidence of adequate tissue perfusion which include continuation of urine output > or = 0.5 ml/kg/hour for 2 hours or decreasing of serum lactate > or = 10 percent in 1 to 2 hours.
Measured: 6 hours
Secondary outcomes (1)
Mortality rate
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 posted19 Sep 2013 (estimated)
- Study start3 Oct 2013
- Primary completionAug 2017
- Study completionAug 2017
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 Septic ShockStudies of the same condition, open and under way.
- More trials run by Mahidol 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 310 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mahidol University
- Sponsor type
- University, hospital or other
- Collaborators
- Siriraj Hospital
- Responsible party
- Sponsor
- Investigators
- Chairat Permpikul, MD, Principal investigator, Mahidol University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01945983
- Sponsor's protocol ID
- Si507/2013
- Acronym
- CENSER
- Status last verified
- Jan 2018
- First submitted
- 16 Sep 2013
- Last updated
- 9 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af.
PubMed 23353941Permpikul 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 30704260
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Comparison Between Early Norepinephrine Use and Standard Treatment During Severe Sepsis and Septic Shock Resuscitation.
- ClinicalTrials.gov ID
- NCT01945983
- Acronym / sponsor ID
- CENSER / Si507/2013
- Conditions
- Septic Shock, Severe Sepsis
- Keywords
- Septic shock, Severe sepsis, Norepinephrine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 310 participants (actual)
- Lead sponsor
- Mahidol UniversityUniversity, hospital or other
- Collaborators
- Siriraj Hospital
- Study start
- 3 Oct 2013 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 19 Sep 2013 (estimated)
- 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.
Current septic shock guideline recommends fluid resuscitation as the first treatment. Vasopressors, including norepinephrine is recommended to start after achieve adequate fluid therapy. This can cause a certain duration of systemic hypotension before vasopressor is commenced. Initiation of norepinephrine together with fluid therapy soon after diagnosis of septic shock may increase blood pressure quicker than start treatment with intravenous fluid alone. The rapid restoration of perfusion pressure may improve septic shock outcome.
Detailed description
We will include severe infection patient who had evidence of organ dysfunction and hypotension and randomize into 2 groups as following:
- Control group. The patient will receive treatment according to septic shock guideline 2013, which start with intravenous fluid replacement until achieve target central venous pressure (CVP) or pulmonary capillary wedge pressure (PCWP) or other fluid responsive test goal. If the patient's mean arterial blood pressure still lower than 65 mmHg, then norepinephrine or dopamine will initiate to rise blood pressure. The patient will receive 5% dextrose water as the placebo of norepinephrine.
- Early norepinephrine group. The patient will receive fluid therapy together with low dose of norepinephrine (0.05 mcg/kg/min). If after titrate intravenous fluid therapy until achieve goal CVP or PCWP or other fluid responsive test, but the mean blood pressure still lower than 65 mmHg, then additional titrate dose of norepinephrine will be given to the patient according to standard septic shock guideline.
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 |
|---|---|---|
| Early norepinephrine | Active comparator | Drug: Early norepinephrineNorepinephrine 4 mg in 5% dextrose water 250 ml Intravenous infusion rate range from 8 to 15 ml/hour, adjusted according to patient's body weight to achieve norepinephrine 0.05microgram/kg/min Continuous drip for 48 hours. |
| Placebo | Placebo comparator | Drug: Placebo5% dextrose water 250 ml Intravenous infusion rate range from 8 to 15 ml/hour. Adjust rate of infusion according to patient's body weight to achieve dosage of norepinephrine comparable to 0.05 microgram/kg/min Continuous drip for 48 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age > or = 18 years old
- Diagnosed severe sepsis or septic shock according to survival sepsis campaign 2013
- Mean arterial pressure < 65 mmHg
Key exclusion criteria (4 listed)
- Pregnancy
- Severe underlying condition that unexpected to survive more than 48 hours
- Severe peripheral vascular disease
- Patient who required major surgery within 24 hours
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 |
|---|---|---|
| Early norepinephrineAlso: Early vasopressor therapyInitiation of norepinephrine, a strong vasoconstrictor, at the initiation of septic shock management, together with fluid resuscitation. | Drug | Early norepinephrine |
| PlaceboAlso: 5%D/W infusion as the placebo of norepinephrine.5% dextrose water intravenous drip in the same rate of calculated norepinephrine for the patient's body weight | Drug | Placebo |
Primary outcome
Therapeutic goal achievement
Time frame: 6 hours
Therapeutic goal including 1. Mean arterial blood pressure > or = 65 mmHg 2. Evidence of adequate tissue perfusion which include continuation of urine output > or = 0.5 ml/kg/hour for 2 hours or decreasing of serum lactate > or = 10 percent in 1 to 2 hours.
1 secondary outcome
Mortality rate
Time frame: 28 days
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 9 Jan 2018.
- Results publication: PubMed 23353941Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af.
- Derived from this study: 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.
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Sepsis
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.
Chairat Permpikul, MD principal investigator
Mahidol University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Early norepinephrine in people with Septic Shock and Severe Sepsis, run by Mahidol University at 1 site in Thailand.
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 3 inclusion and 4 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 9 Jan 2018. 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 Thailand. 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.
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?
Therapeutic goal achievement (time frame: 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 NCT01945983, 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 9 Jan 2018.