Septic ShockRIFTSNCT03137446
Restrictive Intravenous Fluids Trial in Sepsis
A study testing Intravenous Fluid Cap in people with Septic Shock and Severe Sepsis, run by Rhode Island Hospital at 1 site in United States.
Trial summary
IV fluid resuscitation has long been recognized to be an important treatment for patients with severe sepsis and septic shock. While under-resuscitation is known to increase morbidity and mortality, contemporary data suggests that overly aggressive fluid resuscitation may also be harmful. 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?
- Intravenous Fluid Cap
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Apr 2017to 30 Mar 2018
- 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
- The patients must be suspected by the treating physician to have sepsis causing their acute illness as exhibited by 2 or more of the following Systemic Inflammatory Response Syndrome (SIRS) criteria was well as a known or suspected infection at the time of screening:
- Temperature of > 38 C or < 36 C
- Heart rate of > 90/min
- Respiratory rate of > 20/min or PaCO2 < 32 mm Hg
- White blood cell count > 12000/mm3 or < 4000/mm3 or >10% immature bands.
- Since approximately 12% of patients ultimately diagnosed with sepsis do not meet SIRS criteria , SIRS negative patients will be eligible for the study if the treating physician makes a clinical diagnosis of severe sepsis or septic shock.
- Patients must be suspected of having severe sepsis or septic shock defined as refractory hypotension or a lactic acid>4 at the time of enrollment. Refractory hypotension is defined as having a SBP <90 or MAP <65, for 15 minutes, following 1000 mL of IV fluid or a blood pressure maintained by vasopressor administration.
- Patients must have received less than 60ml/kg of intravenous fluid at time of study enrollment.
Who cannot join
- Patients with a PRIMARY diagnosis of acute cerebral vascular event, acute coronary syndrome, acute pulmonary edema, status asthmaticus, active gastrointestinal bleeding, seizure, drug overdose, burn, trauma, requirement for immediate surgery, or undergoing extracorporeal membrane oxygenation.
- Patients who have a diagnosis of severe sepsis or septic shock and additionally have an active fluid wasting process such as extensive diarrhea, diabetes insipidus, cerebral salt wasting, or an osmotic diuresis.
- Patients who have a diagnosis of severe sepsis or septic shock who have a concurrent diagnosis of diabetic ketoacidosis, hyperosmolar non-ketotic hyperglycemia, or rhabdomyolysis.
- Patients who have received >60 ml/kg of IVF resuscitation.
- Patient who are <18 years old, pregnant, or incarcerated.
Trial locations and contacts
1 site in 1 country.
United States1 site
Rhode Island Hosptial
Providence, Rhode Island, 02903
About this study
Official title: Assessing Targeted Fluid Resuscitation Strategies Among Patients With Severe Sepsis and Septic Shock
IV fluid resuscitation has long been recognized to be an important treatment for patients with severe sepsis and septic shock. While under-resuscitation is known to increase morbidity and mortality, contemporary data suggests that overly aggressive fluid resuscitation may also be harmful. Currently, following an initial IVF resuscitation of 30 ml/kg, there is no standard of care and a lack of evidence to support a fluid restrictive or more liberal strategy. The investigators seek to determine if a fluid restrictive strategy reduces morbidity and mortality among patients with severe sepsis and septic shock.
Read the detailed description
Sepsis is one of the most common indications for intensive care unit admission world wide and the third leading cause of death in the United States. While IV fluid administration has been recognized as an important part of sepsis resuscitation for over 15 years, there is growing concern that overly aggressive IV fluid resuscitation may be harmful to patients with severe sepsis and septic shock.
The current standard of care for initial resuscitation is outlined in the 2016 Surviving Sepsis guidelines which recommends a 30mL/kg bolus of IV fluid for septic patients with hypotension (mean arterial pressure <65 mm Hg) or a lactic acid >4mmol/L within the first 3 hours of presentation. This standard is affirmed by the 2015 Centers for Medicare \& Medicaid (CMS) SEP-1 guidelines. Afterwards, the guidelines advise the use of vasopressors to maintain a mean arterial pressure (MAP) of >65 mm Hg within the first 6 hours of patient care. Following the initial 30mL/kg bolus, there is no established standard of care for fluid administration; therefore there is significant variation in care between providers and institutions. Currently, there is no human data that indicates that larger volume (>30mL/kg) resuscitation strategy improves blood pressure or end organ perfusion , yet it is not uncommon for patients to receive large volumes of IV fluid (5-10 liters) in the early stages of resuscitation.
When considering how much IV fluids are typically administered to patients with septic shock, examination of the large EGDT RCTs provides a more informed picture. In the original Rivers study patients received approximately 70 mL/kg of IVF in the first 6 hours and additional 125 ml/kg in hours 7 to 72.3 Notably, this large volume resuscitation did not produce increased rates of clinically important heart failure and intubation. In the contemporary EGDT validation trials, patients received 60-70 ml/kg of IVF in the first 6 hours and only 60-70 ml/kg from hours 7 to 72.6,7,8 The contemporary alternative approach being advocated among critical care practitioners is to use vasopressors to maintain a mean arterial pressures above 65 mm Hg following the initial 30 ml/kg bolus, thereby maintaining organ perfusion, while limiting further IV fluid administration.9 Without clear evidence to guide physicians under current usual care the amount of IV fluid administration varies widely between providers and institutions when resuscitating patients with severe sepsis and septic shock.
The investigators hypothesize the use of a fluid restrictive strategy will result in a lower 28-day mortality, ICU length of stay and total number of ventilator days but will not reduce the number of patients who need hemodialysis or require intubation.
The primary outcome of the study is to assess if a restrictive IV fluid resuscitation strategy has a composite benefit of a reduced discharge mortality or Persistent Organ Dysfunction (POD) score compared to a usual care among patients with severe sepsis and septic shock. POD is defined by the ongoing need for vasopressor agents such as norepinephrine, epinephrine, vasopressin or dopamine for more than two hours in a given day; persistent renal failure as defined by the need for any ongoing renal replacement therapy; and persistent respiratory/neuromuscular failure as defined by the ongoing need for mechanical ventilation (not including non-invasive ventilation modalities).
- Conditions
- Septic Shock, Severe Sepsis
- Being tested
- Intravenous Fluid Cap
- Keywords
- Intravenous fluid resuscitation, Septic shock, Severe sepsis, Fluid restriction
- 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.
Intravenous Fluid CapOther
Normal Saline or Ringers Lactate limited to 60ml/kg for first 72 hours
| Study group | Role | What they receive |
|---|---|---|
| Usual Care | No intervention | Participants randomized to the usual care resuscitation strategy will receive an initial 30 ml/kg bolus and then IV fluids as needed and without limit as well as IV vasopressors to maintain a MAP>65, determined by the primary care team for the duration of the study. |
| Restrictive Care | Experimental | Participants randomized to the restrictive fluid resuscitation strategy will be LIMITED to 60 ml/kg (up to 6000 ml) of IV fluids as initial resuscitation followed by administration of IV vasopressors to maintain a MAP>65 mm Hg for the first 72 hours of care. The intervention is defined as capping the total allowed IVF administered. After 72 hours the participants are eligible for IV fluids as determined by the primary care team. Receives: Other: Intravenous Fluid Cap |
What is being measured
The primary outcome is the main question the study is designed to answer.
Discharge Mortality and Persistent Organ Dysfunction (POD) a composite outcome
Persistent Organ Dysfunction is defined as the ongoing need for vasopressor agents such as norepinephrine, epinephrine, vasopressin or dopamine for more than two hours in a given day; persistent renal failure as defined by the need for any ongoing renal replacement therapy; or persistent respiratory failure as defined by the ongoing need for mechanical ventilation at least 2 hours a day. The composite outcome will be defined as having at least one of the 4 possible composite outcomes (death, vasopressor support, persistent renal failure, or persistent respiratory failure). If a patient has one or more of these outcomes they will be classified as having the primary composite outcome. If the patient has 0 of 4 outcomes they will be classified as not having the composite outcome.
Measured: At participant hospital discharge or up to 60 days
Secondary outcomes (9)
7 day Mortality and Persistent Organ Dysfunction
Persistent Organ Dysfunction is defined as the ongoing need for vasopressor agents such as norepinephrine, epinephrine, vasopressin or dopamine for more than two hours in a given day; persistent renal failure as defined by the need for any ongoing renal replacement therapy; or persistent respiratory failure as defined by the ongoing need for mechanical ventilation at least 2 hours a day. The composite outcome will be defined as having at least one of the 4 possible composite outcomes (death, vasopressor support, persistent renal failure, or persistent respiratory failure). If a patient has one or more of these outcomes they will be classified as having the secondary composite outcome. If the patient has 0 of 4 outcomes they will be classified as not having the composite outcome.
Measured: Day 7
30 day Mortality and Persistent Organ Dysfunction
Persistent Organ Dysfunction is defined as the ongoing need for vasopressor agents such as norepinephrine, epinephrine, vasopressin or dopamine for more than two hours in a given day; persistent renal failure as defined by the need for any ongoing renal replacement therapy; or persistent respiratory failure as defined by the ongoing need for mechanical ventilation at least 2 hours a day. The composite outcome will be defined as having at least one of the 4 possible composite outcomes (death, vasopressor support, persistent renal failure, or persistent respiratory failure). If a patient has one or more of these outcomes they will be classified as having the secondary composite outcome. If the patient has 0 of 4 outcomes they will be classified as not having the composite outcome.
Measured: Day 30
60 day Mortality and Persistent Organ Dysfunction
Persistent Organ Dysfunction is defined as the ongoing need for vasopressor agents such as norepinephrine, epinephrine, vasopressin or dopamine for more than two hours in a given day; persistent renal failure as defined by the need for any ongoing renal replacement therapy; or persistent respiratory failure as defined by the ongoing need for mechanical ventilation at least 2 hours a day. The composite outcome will be defined as having at least one of the 4 possible composite outcomes (death, vasopressor support, persistent renal failure, or persistent respiratory failure). If a patient has one or more of these outcomes they will be classified as having the secondary composite outcome. If the patient has 0 of 4 outcomes they will be classified as not having the composite outcome.
Measured: Day 60
Intensive Care Unit length of stay
Number of hours the participant spends in the ICU
Measured: up to 60 days
Length of Shock
Number of hours of shock requiring vasopressors
Measured: up to 60 days
Requirement for renal replacement therapy or reduction of renal failure
Need for intermittent or continuous or intermittent hemodialysis
Measured: up to 60 days
Mechanical Intubation
Proportion of patients intubated during their ICU course
Measured: up to 60 days
Hyperchloremic metabolic acidosis
Development of a non anion gap metabolic acidosis secondary to hyperchloremia
Measured: up to 60 days
Time of mechanical ventilation
For those patients intubated, the number of hours that they received mechanical ventilation
Measured: up to 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2017
- Study start20 Apr 2017
- Primary completion30 Mar 2018
- Study completion30 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Trial
- Masking
- None (open label)
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rhode Island Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Keith Corl, MD, Principal investigator, Department of Pulmonary Critical Care Brown UniversityMitchell Levy, MD, Study chair, Department of Pulmonary Critical Care Brown UniversityAmy Palmisciano, RN, BSN, Study director, Department of Pulmonary Critical Care Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03137446
- Sponsor's protocol ID
- 409916
- Acronym
- RIFTS
- Status last verified
- Jun 2018
- First submitted
- 10 Apr 2017
- Last updated
- 31 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.
PubMed 11445675Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb;34(2):344-53. doi: 10.1097/01.ccm.0000194725.48928.3a.
PubMed 16424713Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307.
PubMed 11794169Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Aneman A, Vang ML, Winding R, Nebrich L, Nibro HL, Rasmussen BS, Lauridsen JR, Nielsen JS, Oldner A, Pettila V, Cronhjort MB, Andersen LH, Pedersen UG, Reiter N, Wiis J, White JO, Russell L, Thornberg KJ, Hjortrup PB, Muller RG, Moller MH, Steensen M, Tjader I, Kilsand K, Odeberg-Wernerman S, Sjobo B, Bundgaard H, Thyo MA, Lodahl D, Maerkedahl R, Albeck C, Illum D, Kruse M, Winkel P, Perner A; TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014 Oct 9;371(15):1381-91. doi: 10.1056/NEJMoa1406617. Epub 2014 Oct 1.
PubMed 25270275Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. doi: 10.1001/jama.2010.158.
PubMed 20179283ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. doi: 10.1056/NEJMoa1401602. Epub 2014 Mar 18.
PubMed 24635773Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM; ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. doi: 10.1056/NEJMoa1500896. Epub 2015 Mar 17.
PubMed 25776532ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, Higgins AM, Holdgate A, Howe BD, Webb SA, Williams P. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. doi: 10.1056/NEJMoa1404380. Epub 2014 Oct 1.
PubMed 25272316Marik PE. Early management of severe sepsis: concepts and controversies. Chest. 2014 Jun;145(6):1407-1418. doi: 10.1378/chest.13-2104.
PubMed 24889440Dellinger 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 S, 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. Intensive Care Med. 2013 Feb;39(2):165-228. doi: 10.1007/s00134-012-2769-8. Epub 2013 Jan 30.
PubMed 23361625Hilton AK, Bellomo R. A critique of fluid bolus resuscitation in severe sepsis. Crit Care. 2012 Jan 25;16(1):302. doi: 10.1186/cc11154.
PubMed 22277834Hilton AK, Bellomo R. Totem and taboo: fluids in sepsis. Crit Care. 2011;15(3):164. doi: 10.1186/cc10247. Epub 2011 Jun 10.
PubMed 21672278Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001 Aug 23;345(8):588-95. doi: 10.1056/NEJMra002709. No abstract available.
PubMed 11529214Ueda S, Nishio K, Akai Y, Fukushima H, Ueyama T, Kawai Y, Masui K, Yoshioka A, Okuchi K. Prognostic value of increased plasma levels of brain natriuretic peptide in patients with septic shock. Shock. 2006 Aug;26(2):134-9. doi: 10.1097/01.shk.0000226266.99960.d0.
PubMed 16878020Zhang Z, Zhang Z, Xue Y, Xu X, Ni H. Prognostic value of B-type natriuretic peptide (BNP) and its potential role in guiding fluid therapy in critically ill septic patients. Scand J Trauma Resusc Emerg Med. 2012 Dec 31;20:86. doi: 10.1186/1757-7241-20-86.
PubMed 23276277
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Targeted Fluid Resuscitation Strategies Among Patients With Severe Sepsis and Septic Shock
- ClinicalTrials.gov ID
- NCT03137446
- Acronym / sponsor ID
- RIFTS / 409916
- Conditions
- Septic Shock, Severe Sepsis
- Keywords
- Intravenous fluid resuscitation, Septic shock, Severe sepsis, Fluid restriction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Rhode Island HospitalUniversity, hospital or other
- Study start
- 20 Apr 2017 (actual)
- Primary completion
- 30 Mar 2018 (actual)
- Study completion
- 30 Mar 2018 (actual)
- First posted
- 2 May 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.
IV fluid resuscitation has long been recognized to be an important treatment for patients with severe sepsis and septic shock. While under-resuscitation is known to increase morbidity and mortality, contemporary data suggests that overly aggressive fluid resuscitation may also be harmful. Currently, following an initial IVF resuscitation of 30 ml/kg, there is no standard of care and a lack of evidence to support a fluid restrictive or more liberal strategy. The investigators seek to determine if a fluid restrictive strategy reduces morbidity and mortality among patients with severe sepsis and septic shock.
Detailed description
Sepsis is one of the most common indications for intensive care unit admission world wide and the third leading cause of death in the United States. While IV fluid administration has been recognized as an important part of sepsis resuscitation for over 15 years, there is growing concern that overly aggressive IV fluid resuscitation may be harmful to patients with severe sepsis and septic shock.
The current standard of care for initial resuscitation is outlined in the 2016 Surviving Sepsis guidelines which recommends a 30mL/kg bolus of IV fluid for septic patients with hypotension (mean arterial pressure <65 mm Hg) or a lactic acid >4mmol/L within the first 3 hours of presentation. This standard is affirmed by the 2015 Centers for Medicare \& Medicaid (CMS) SEP-1 guidelines. Afterwards, the guidelines advise the use of vasopressors to maintain a mean arterial pressure (MAP) of >65 mm Hg within the first 6 hours of patient care. Following the initial 30mL/kg bolus, there is no established standard of care for fluid administration; therefore there is significant variation in care between providers and institutions. Currently, there is no human data that indicates that larger volume (>30mL/kg) resuscitation strategy improves blood pressure or end organ perfusion , yet it is not uncommon for patients to receive large volumes of IV fluid (5-10 liters) in the early stages of resuscitation.
When considering how much IV fluids are typically administered to patients with septic shock, examination of the large EGDT RCTs provides a more informed picture. In the original Rivers study patients received approximately 70 mL/kg of IVF in the first 6 hours and additional 125 ml/kg in hours 7 to 72.3 Notably, this large volume resuscitation did not produce increased rates of clinically important heart failure and intubation. In the contemporary EGDT validation trials, patients received 60-70 ml/kg of IVF in the first 6 hours and only 60-70 ml/kg from hours 7 to 72.6,7,8 The contemporary alternative approach being advocated among critical care practitioners is to use vasopressors to maintain a mean arterial pressures above 65 mm Hg following the initial 30 ml/kg bolus, thereby maintaining organ perfusion, while limiting further IV fluid administration.9 Without clear evidence to guide physicians under current usual care the amount of IV fluid administration varies widely between providers and institutions when resuscitating patients with severe sepsis and septic shock.
The investigators hypothesize the use of a fluid restrictive strategy will result in a lower 28-day mortality, ICU length of stay and total number of ventilator days but will not reduce the number of patients who need hemodialysis or require intubation.
The primary outcome of the study is to assess if a restrictive IV fluid resuscitation strategy has a composite benefit of a reduced discharge mortality or Persistent Organ Dysfunction (POD) score compared to a usual care among patients with severe sepsis and septic shock. POD is defined by the ongoing need for vasopressor agents such as norepinephrine, epinephrine, vasopressin or dopamine for more than two hours in a given day; persistent renal failure as defined by the need for any ongoing renal replacement therapy; and persistent respiratory/neuromuscular failure as defined by the ongoing need for mechanical ventilation (not including non-invasive ventilation modalities).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized Trial
| Arm | Type | Receives |
|---|---|---|
| Usual Care | No intervention | –Participants randomized to the usual care resuscitation strategy will receive an initial 30 ml/kg bolus and then IV fluids as needed and without limit as well as IV vasopressors to maintain a MAP>65, determined by the primary care team for the duration of the study. |
| Restrictive Care | Experimental | Other: Intravenous Fluid CapParticipants randomized to the restrictive fluid resuscitation strategy will be LIMITED to 60 ml/kg (up to 6000 ml) of IV fluids as initial resuscitation followed by administration of IV vasopressors to maintain a MAP>65 mm Hg for the first 72 hours of care. The intervention is defined as capping the total allowed IVF administered. After 72 hours the participants are eligible for IV fluids as determined by the primary care team. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The patients must be suspected by the treating physician to have sepsis causing their acute illness as exhibited by 2 or more of the following Systemic Inflammatory Response Syndrome (SIRS) criteria was well as a known or suspected infection at the time of screening:
- Since approximately 12% of patients ultimately diagnosed with sepsis do not meet SIRS criteria , SIRS negative patients will be eligible for the study if the treating physician makes a clinical diagnosis of severe sepsis or septic shock.
- Patients must be suspected of having severe sepsis or septic shock defined as refractory hypotension or a lactic acid>4 at the time of enrollment. Refractory hypotension is defined as having a SBP <90 or MAP <65, for 15 minutes, following 1000 mL of IV fluid or a blood pressure maintained by vasopressor administration.
- Patients must have received less than 60ml/kg of intravenous fluid at time of study enrollment.
Key exclusion criteria (5 listed)
- Patients with a PRIMARY diagnosis of acute cerebral vascular event, acute coronary syndrome, acute pulmonary edema, status asthmaticus, active gastrointestinal bleeding, seizure, drug overdose, burn, trauma, requirement for immediate surgery, or undergoing extracorporeal membrane oxygenation.
- Patients who have a diagnosis of severe sepsis or septic shock and additionally have an active fluid wasting process such as extensive diarrhea, diabetes insipidus, cerebral salt wasting, or an osmotic diuresis.
- Patients who have a diagnosis of severe sepsis or septic shock who have a concurrent diagnosis of diabetic ketoacidosis, hyperosmolar non-ketotic hyperglycemia, or rhabdomyolysis.
- Patients who have received >60 ml/kg of IVF resuscitation.
- Patient who are <18 years old, pregnant, or incarcerated.
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 |
|---|---|---|
| Intravenous Fluid CapNormal Saline or Ringers Lactate limited to 60ml/kg for first 72 hours | Other | Restrictive Care |
Primary outcome
Discharge Mortality and Persistent Organ Dysfunction (POD) a composite outcome
Time frame: At participant hospital discharge or up to 60 days
Persistent Organ Dysfunction is defined as the ongoing need for vasopressor agents such as norepinephrine, epinephrine, vasopressin or dopamine for more than two hours in a given day; persistent renal failure as defined by the need for any ongoing renal replacement therapy; or persistent respiratory failure as defined by the ongoing need for mechanical ventilation at least 2 hours a day. The composite outcome will be defined as having at least one of the 4 possible composite outcomes (death, vasopressor support, persistent renal failure, or persistent respiratory failure). If a patient has one or more of these outcomes they will be classified as having the primary composite outcome. If the patient has 0 of 4 outcomes they will be classified as not having the composite outcome.
9 secondary outcomes
7 day Mortality and Persistent Organ Dysfunction
Time frame: Day 7
30 day Mortality and Persistent Organ Dysfunction
Time frame: Day 30
60 day Mortality and Persistent Organ Dysfunction
Time frame: Day 60
Intensive Care Unit length of stay
Time frame: up to 60 days
Length of Shock
Time frame: up to 60 days
Requirement for renal replacement therapy or reduction of renal failure
Time frame: up to 60 days
Mechanical Intubation
Time frame: up to 60 days
Hyperchloremic metabolic acidosis
Time frame: up to 60 days
Time of mechanical ventilation
Time frame: up to 60 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 31 Aug 2018.
- Background: PubMed 11445675Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.
- Background: PubMed 16424713Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb;34(2):344-53. doi: 10.1097/01.ccm.0000194725.48928.3a.
- Background: PubMed 11794169Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307.
- Background: PubMed 25270275Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Aneman A, Vang ML, Winding R, Nebrich L, Nibro HL, Rasmussen BS, Lauridsen JR, Nielsen JS, Oldner A, Pettila V, Cronhjort MB, Andersen LH, Pedersen UG, Reiter N, Wiis J, White JO, Russell L, Thornberg KJ, Hjortrup PB, Muller RG, Moller MH, Steensen M, Tjader I, Kilsand K, Odeberg-Wernerman S, Sjobo B, Bundgaard H, Thyo MA, Lodahl D, Maerkedahl R, Albeck C, Illum D, Kruse M, Winkel P, Perner A; TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014 Oct 9;371(15):1381-91. doi: 10.1056/NEJMoa1406617. Epub 2014 Oct 1.
- Background: PubMed 20179283Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. doi: 10.1001/jama.2010.158.
- Background: PubMed 24635773ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. doi: 10.1056/NEJMoa1401602. Epub 2014 Mar 18.
- Background: PubMed 25776532Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM; ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. doi: 10.1056/NEJMoa1500896. Epub 2015 Mar 17.
- Background: PubMed 25272316ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, Higgins AM, Holdgate A, Howe BD, Webb SA, Williams P. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. doi: 10.1056/NEJMoa1404380. Epub 2014 Oct 1.
- Background: PubMed 24889440Marik PE. Early management of severe sepsis: concepts and controversies. Chest. 2014 Jun;145(6):1407-1418. doi: 10.1378/chest.13-2104.
- Background: PubMed 23361625Dellinger 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 S, 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. Intensive Care Med. 2013 Feb;39(2):165-228. doi: 10.1007/s00134-012-2769-8. Epub 2013 Jan 30.
- Background: PubMed 22277834Hilton AK, Bellomo R. A critique of fluid bolus resuscitation in severe sepsis. Crit Care. 2012 Jan 25;16(1):302. doi: 10.1186/cc11154.
- Background: PubMed 21672278Hilton AK, Bellomo R. Totem and taboo: fluids in sepsis. Crit Care. 2011;15(3):164. doi: 10.1186/cc10247. Epub 2011 Jun 10.
- Individual participant dataSharing planned: Undecided
Related trials for Septic Shock
Recruiting
Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock
Sepsis - to Reduce Mortality in the Intensive Care Unit, Septic Shock
Not yet recruiting
Hemodynamic Resuscitation Guided by Non-Invasive Mean Systemic Filling Pressure to Prevent Acute Kidney Injury in Septic Shock
Acute Kidney Injury Due to Sepsis
RecruitingObservational study
Clinical Value of EMR3 in Sepsis Diagnosis, Monitoring, and Prognosis: A Multicenter Prospective Observational Study
Sepsis
RecruitingObservational study
Comparison of Cardiac Index Measurement Using Right Ventricular Pressure Curve Analysis and Thermodilution Via a Swan-Ganz IQ™ Catheter.
Septic Shock
RecruitingPhase 3
A Trial of Adjunctive Fludrocortisone (50mcg, 100mcg or Placebo) in Critically Ill Patients With Septic Shock Receiving Hydrocortisone, Evaluating Survival and Functional Recovery and the Influence of Transcriptomic Response
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.
Keith Corl, MD principal investigator
Department of Pulmonary Critical Care Brown University
Mitchell Levy, MD study chair
Department of Pulmonary Critical Care Brown University
Amy Palmisciano, RN, BSN study director
Department of Pulmonary Critical Care Brown 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 Intravenous Fluid Cap in people with Septic Shock and Severe Sepsis, run by Rhode Island Hospital at 1 site in United States.
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 8 inclusion and 5 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 31 Aug 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 United States. 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?
Discharge Mortality and Persistent Organ Dysfunction (POD) a composite outcome (time frame: At participant hospital discharge or up to 60 days). 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 NCT03137446, which also lists 25 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 31 Aug 2018.