Septic ShockPhase 2TERESEPNCT04339868
Terlipressin for Refractory Septic Shock
A Phase 2 study testing Terlipressin in people with Septic Shock and Refractory Shock, run by Mahidol University at 1 site in Thailand.
Trial summary
Norepinephrine was recommended as the first vasopressor for septic shock resuscitation. For the patient who did not response to high dose norepinephrine, epinephrine was recommended. Vasopressin was also recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Refractory Shock, Norepinephrine Adverse Reaction
- What is being tested?
- Terlipressin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 1 siteThailand
- Study dates
- 3 Apr 2020to 31 Jul 2025
- Phase
- Phase 2
- 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
- Septic shock according to Sepsis-3 definition
- Evidence of adequate fluid
- Received norepinephrine 0.2 mcg/kg/min or more
- Received norepinephrine plus epinephrine (any dose)
- Mean arterial lower than 65 mmHg or lactate > 2 mmol/liter
Who cannot join
- Septic shock diagnosis > 48 hours before
- Receive intravenous fluid < 30 mL/kg before enrollment
- Do-not-resuscitation and terminally ill
- Refractory to treatment malignancy
- Pregnancy
- 7. Chronic renal failure stage 5 with no plan for long term renal replacement therapy 8. Cirrhosis child C 9. Cardiogenic shock 10. Acute decompensated heart failure 11. Evidence of left ventricular ejection fraction (LVEF) < 35% 12. Acute coronary syndrome within 72 hours 13. Severe valvular heart disease 14. Documented life-threatening tachyarrhythmia before enrollment 15. Diagnosis of acute mesenteric ischemia before enrollment 16. Previous diagnosis of Raynaud's phenomenon 17. Known peripheral arterial disease 18. Refuse to sign the informed consent by patient or representative
Trial locations and contacts
1 site in 1 country.
Thailand1 site, 1 recruiting
- Recruiting
Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University
Bangkok, 10700
Surat Tongyoo, MD, 6624198534, surat.ton@mahidol.ac.th
Chawanee Chayakul, MD, 080-440-1137, jingjaring@gmail.com
About this study
Official title: Terlipressin Versus Placebo for Septic Shock Refractory to High Doses Catecholamine Vasopressors: A Randomized-controlled Trial
Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.
For the patient who did not response to high dose norepinephrine, epinephrine was recommended.
Read more
Vasopressin was also recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine.
Terlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine.
To use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.
Read the detailed description
Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.
For the patient who did not response to high dose norepinephrine, epinephrine was recommended.
Both norepinephrine and epinephrine action via the alpha adrenergic stimuli to increase vascular smooth muscle contraction, induced vasoconstriction and increase arterial blood pressure. It also action via beta adrenergic stimuli, to increase heart rate and myocardial contractility, then increase stroke volume and cardiac output.
Too much alpha and beta adrenergic stimulation, especially during received high dose norepinephrine and or epinephrine associated with vasoconstriction induce organs ischemia.
The most common organ ischemia included myocardial ischemia, bowel ischemia and limbs ischemia.
Cardiac arrhythmia was also the most common complication associated with high dose norepinephrine and or epinephrine.
Atrial fibrillation was the most common reported arrhythmia, however, fatal arrhythmia included ventricular fibrillation and tachycardia were also reported.
Vasopressin was recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine.
Terlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine.
To use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.
The benefit effect of terlipressin could be demonstrated when prescribe among the septic shock patients who required high dose of adrenergic vasoactive agents.
Terlipressin plus norepinephrine and or epinephrine could maintain or even improve blood pressure and tissue perfusion with lower fatal side effects than norepinephrine and or epinephrine without terlipressin.
- Being tested
- Terlipressin, Placebo
- Medical subject headings
- Shock, Septic, Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TerlipressinDrug
Terlipressin (20-100 mcg/hr) plus norepinephrine and/or epinephrine
PlaceboDrug
0.9% NaCl plus norepinephrine and/or epinephrine
| Study group | Role | What they receive |
|---|---|---|
| Terlipressin group | Active comparator | Terlipressin acetate 1 mg in 0.9% normal saline (NaCl) 50 mL (0.02 mg/mL) Initial dose 20 mcg/hr (1 mL/hr) titrate increase 1 mL/hr every 30 min to 100 mcg/hr (5 mg/hr) to keep mean arterial blood pressure (MAP) > 65 mmHg If MAP > 75 mmHg for > 30 min, decrease epinephrine and norepinephrine until < 0.15 mcg/kg/min, then decrease terlipressin until stop Receives: Drug: Terlipressin |
| Placebo group | Placebo comparator | Placebo 0.9% NaCl 50 mL Initial dose 1 mL/hr titrate increase 1 mL/hr every 30 min to 5 mg/hr to keep mean arterial blood pressure (MAP) > 65 mmHg If MAP > 75 mmHg for > 30 min, decrease epinephrine and norepinephrine until < 0.15 mcg/kg/min, then decrease placebo until stop Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Achieve target blood pressure with low dose adrenergic agents
Achieve target mean arterial blood pressure 65 millimeter mercury or more with norepinephrine and/or epinephrine dose 0.2 mcg/kg/min or lower
Measured: 6 hours after initiate study drug
Secondary outcomes (4)
28 day mortality
Proportion of patient who dead before 28 days after enrollment
Measured: 28 days
Mean arterial blood pressure
Mean arterial blood pressure after initiate study drug
Measured: 72 hours
Hospital mortality
Proportion of patient who dead before hospital discharge after enrollment
Measured: 90 days
ICU mortality
Proportion of patient who dead before ICU discharge after enrollment
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2020
- Study start3 Apr 2020
- Primary completion31 Mar 2025 (estimated)
- Study completion31 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Intervention arm: Terlipressin plus Norepinephrine and/or Epinephrine Controlled arm: Placebo plus Norepinephrine and/or Epinephrine for Treatment Refractory Septic Shock
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mahidol University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Surat Tongyoo, MD, Principal investigator, Mahidol University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04339868
- Sponsor's protocol ID
- Si 049/2020
- Acronym
- TERESEP
- Status last verified
- Sep 2021
- First submitted
- 7 Apr 2020
- Last updated
- 24 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data set and analysis are available from the corresponding author on reasonable request.
Publications
Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
PubMed 28101605Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
PubMed 26903338Permpikul 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 24 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Terlipressin Versus Placebo for Septic Shock Refractory to High Doses Catecholamine Vasopressors: A Randomized-controlled Trial
- ClinicalTrials.gov ID
- NCT04339868
- Acronym / sponsor ID
- TERESEP / Si 049/2020
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Mahidol UniversityUniversity, hospital or other
- Study start
- 3 Apr 2020 (actual)
- Primary completion
- 31 Mar 2025 (estimated)
- Study completion
- 31 Jul 2025 (estimated)
- First posted
- 9 Apr 2020 (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.
Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.
For the patient who did not response to high dose norepinephrine, epinephrine was recommended.
Vasopressin was also recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine.
Terlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine.
To use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.
Detailed description
Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.
For the patient who did not response to high dose norepinephrine, epinephrine was recommended.
Both norepinephrine and epinephrine action via the alpha adrenergic stimuli to increase vascular smooth muscle contraction, induced vasoconstriction and increase arterial blood pressure. It also action via beta adrenergic stimuli, to increase heart rate and myocardial contractility, then increase stroke volume and cardiac output.
Too much alpha and beta adrenergic stimulation, especially during received high dose norepinephrine and or epinephrine associated with vasoconstriction induce organs ischemia.
The most common organ ischemia included myocardial ischemia, bowel ischemia and limbs ischemia.
Cardiac arrhythmia was also the most common complication associated with high dose norepinephrine and or epinephrine.
Atrial fibrillation was the most common reported arrhythmia, however, fatal arrhythmia included ventricular fibrillation and tachycardia were also reported.
Vasopressin was recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine.
Terlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine.
To use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.
The benefit effect of terlipressin could be demonstrated when prescribe among the septic shock patients who required high dose of adrenergic vasoactive agents.
Terlipressin plus norepinephrine and or epinephrine could maintain or even improve blood pressure and tissue perfusion with lower fatal side effects than norepinephrine and or epinephrine without terlipressin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Intervention arm: Terlipressin plus Norepinephrine and/or Epinephrine Controlled arm: Placebo plus Norepinephrine and/or Epinephrine for Treatment Refractory Septic Shock
| Arm | Type | Receives |
|---|---|---|
| Terlipressin group | Active comparator | Drug: TerlipressinTerlipressin acetate 1 mg in 0.9% normal saline (NaCl) 50 mL (0.02 mg/mL) Initial dose 20 mcg/hr (1 mL/hr) titrate increase 1 mL/hr every 30 min to 100 mcg/hr (5 mg/hr) to keep mean arterial blood pressure (MAP) > 65 mmHg If MAP > 75 mmHg for > 30 min, decrease epinephrine and norepinephrine until < 0.15 mcg/kg/min, then decrease terlipressin until stop |
| Placebo group | Placebo comparator | Drug: PlaceboPlacebo 0.9% NaCl 50 mL Initial dose 1 mL/hr titrate increase 1 mL/hr every 30 min to 5 mg/hr to keep mean arterial blood pressure (MAP) > 65 mmHg If MAP > 75 mmHg for > 30 min, decrease epinephrine and norepinephrine until < 0.15 mcg/kg/min, then decrease placebo until stop |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Septic shock according to Sepsis-3 definition
- Evidence of adequate fluid
- Received norepinephrine 0.2 mcg/kg/min or more
- Received norepinephrine plus epinephrine (any dose)
- Mean arterial lower than 65 mmHg or lactate > 2 mmol/liter
Key exclusion criteria (6 listed)
- Septic shock diagnosis > 48 hours before
- Receive intravenous fluid < 30 mL/kg before enrollment
- Do-not-resuscitation and terminally ill
- Refractory to treatment malignancy
- Pregnancy
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 |
|---|---|---|
| TerlipressinTerlipressin (20-100 mcg/hr) plus norepinephrine and/or epinephrine | Drug | Terlipressin group |
| Placebo0.9% NaCl plus norepinephrine and/or epinephrine | Drug | Placebo group |
Primary outcome
Achieve target blood pressure with low dose adrenergic agents
Time frame: 6 hours after initiate study drug
Achieve target mean arterial blood pressure 65 millimeter mercury or more with norepinephrine and/or epinephrine dose 0.2 mcg/kg/min or lower
4 secondary outcomes
28 day mortality
Time frame: 28 days
Mean arterial blood pressure
Time frame: 72 hours
Hospital mortality
Time frame: 90 days
ICU mortality
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2021.
- Results publication: PubMed 28101605Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
- Results publication: PubMed 26903338Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
- Results publication: 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.
- Individual participant dataSharing planned: Yes. The data set and analysis are available from the corresponding author on reasonable request.
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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.
Surat Tongyoo, 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 Phase 2 study testing Terlipressin in people with Septic Shock and Refractory Shock, 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 5 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: status not confirmed, as of the sponsor's last update on 24 Sep 2021. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Surat Tongyoo, MD (0820137771, surat.ton@mahidol.ac.th), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Achieve target blood pressure with low dose adrenergic agents (time frame: 6 hours after initiate study drug). 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 NCT04339868, which also lists 3 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 24 Sep 2021.