Intensive Care Unit Acquired WeaknessANDROMEDA-FRNCT06062303
Hemodynamic Phenotype-Based,Capillary Refill Time-Targeted Resuscitation In Early Septic Shock:ANDROMEDA-SHOCK-2
A study of Intensive Care Unit Acquired Weakness and Shock, Septic, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Over-resuscitation including fluid overload has been associated with increased morbidity (prolonged duration of organ failure) and mortality in septic shock. "One-size-fits-all" resuscitation strategies may increase septic shock mortality. However, clinical studies on individualized resuscitation are lacking. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intensive Care Unit Acquired Weakness, Shock, Septic
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteFrance
- Study dates
- 6 Feb 2024to 30 May 2026
- Phase
- Interventional
- 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
- Consecutive adult patients (≥ 18 years)
- Patients with septic shock according to Sepsis-3 consensus conference. In short, septic shock is defined as suspected or confirmed infection, plus hyperlactatemia and NE requirements due to persistent hypotension, after a fluid load of at least 1000mL in 1h
- Patient and/or relative informed and having signed the information and consent form for participation in the study
Who cannot join
- More than 4 hours since septic shock diagnosis,
- Anticipated surgery or acute hemodialysis procedure to start during the 6h intervention period
- Active bleeding,
- Do not resuscitate status,
- Child B-C Cirrhosis
- Underlying disease process with a life expectancy < 90 days and/or the attending clinician deems aggressive resuscitation unsuitable
Show all 15Show fewer
- Refractory shock (high risk of death within 24h)
- Pregnancy
- Concomitant severe acute respiratory distress syndrome
- Patients in whom CRT cannot be accurately assessed
- Non-affiliation to a social security scheme or to another social protection scheme
- Patient on AME (state medical aid) (unless exemption from affiliation
- Patient under legal protection (guardianship, curatorship)
- Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants, if applicable
- Inability, according to the investigator, to understand the study (non-French-speaking patient, cognitive disorders)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital Robert Debré, Université de Reims
Reims, 51092
Hamzaoui MD Olfa, PhD, 0033310736973, ohamzaoui@chu-reims.fr
About this study
Official title: Hemodynamic Phenotype-Based, Capillary Refill Time-Targeted Resuscitation In Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial (A2)
Over-resuscitation including fluid overload has been associated with increased morbidity (prolonged duration of organ failure) and mortality in septic shock. "One-size-fits-all" resuscitation strategies may increase septic shock mortality. However, clinical studies on individualized resuscitation are lacking. Hemodynamic phenotyping may allow to individualize septic shock resuscitation. The ANDROMEDA-SHOCK trial found that a simple clinical and bedside CRT-targeted resuscitation reduces organ dysfunction and 28-day mortality in septic shock. The current study will examine the hypothesis that a CRT-targeted resuscitation based on hemodynamic phenotyping considering within an decision tree usual bedside clinical parameters such as pulse pressure, diastolic blood pressure, fluid responsiveness and cardiac performance can further decrease mortality in septic shock as compared to usual care.
Read the detailed description
Septic shock is associated with a high mortality risk related to progressive tissue hypoperfusion.However, despite extensive research on the best monitoring and resuscitation strategies, many uncertainties remain. Over-resuscitation, particularly when inducing fluid overload, might contribute to a worse outcome. Fluid overload more likely occurs when fluids are administered to fluid unresponsive patients, but also when inappropriate resuscitation goals are pursued, or a "one-size-fit all" strategy is followed. From a hemodynamic point of view, several pathogenic mechanisms determine a progressive circulatory dysfunction While loss of vascular tone and relative hypovolemia predominate in early phases, more complex mechanisms such as endothelial and microcirculatory dysfunction, progressive vasoplegia, and myocardial dysfunction may be involved later. In effect, from a clinical point of view, many patients despite been fluid loaded in pre-intensive care unit settings, are still evidently hypovolemic and benefit from further administration of fluid boluses. Others, however, present very low diastolic arterial pressures reflecting profound vasoplegia, and recent data suggest that these patients may benefit from early norepinephrine instead of fluids[; on the contrary, administering fluids may fail to correct vascular tone and increase the risk of fluid overload[2]. In addition, a recent echocardiography-based study confirms that a relevant myocardial dysfunction is present in a significant number of patients, and that several cardiovascular phenotypes with a potentially different therapeutic approach may be recognized[8]. Unfortunately, despite the availability of most of the parameters at the bedside and research efforts, no universally applicable clinical phenotyping method for septic shock patients has been translated to usual practice. This is particularly problematic since chocardiography is not immediately available in the majority of centers worldwide, and therefore initial decisions on fluid resuscitation are usually based on clinical grounds and tend to follow the one-size-fits-all principle, leading to the risk of fluid overload.
- Being tested
- Usual care (UC)
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Usual care (UC)Other
- Patients allocated to the UC group will be managed by the clinical staff according to usual practice at their sites including decisions about hemodynamic and perfusion monitoring, and all treatments, but should follow general recommendations of the Surviving Sepsis Campaign to avoid extremes of clinical practice. This includes basic hemodynamic targets such as a MAP >65 mmHg, heart rate (HR) <120 beats per minute (BPM), arterial oxygen saturation (SaO2) >94%, Hb > 7 gr/dl, and the use of NE as the first vasopressor and crystalloids as the fluid of choice.
| Study group | Role | What they receive |
|---|---|---|
| Compartor arm | No intervention | - Patients allocated to the usual care group will be managed by the clinical staff according to usual practice at their sites including decisions about hemodynamic and perfusion monitoring, and all treatments, but should follow general recommendations of the Surviving Sepsis Campaign to avoid extremes of clinical practice. This includes basic hemodynamic targets such as a MAP >65 mmHg, HR (heart rate) <120 beats per minute (BPM), arterial oxygen saturation (SaO2) >94%, Hb > 7 gr/dl, and the use of NE as the first vasopressor and crystalloids as the fluid of choice. |
| Capillary-refill time and phenotyping group | Active comparator | Patients w/normal baseline CRT will be periodically monitored. Patients with abnormal CRT and septic shock will be categorized according to pulse pressure (PP). If <40 mmHg, will go to fluid responsiveness (FR) assessment. FR (-) patients will undergo cardiac echo to rule out significant dysfunction. Fluid boluses will be administered in 30 min intervals and repeated as needed if CRT is still abnormal. Patients with PP ≥40 mmHg will proceed according to diastolic pressure (DAP). If ≥50 mmHg will move to FR assessment. If <50 mmHg NE will be increased for MAP >65 mmHg and DAP ≥50 mmHg w/CRT assessed 1 h after. NE will be increased in 0.1 mcg/k/m increments up to 0.5 mcg/k/m.
If CRT is normal, patients will proceed to periodic monitoring. Patients with persistent abnormal CRT or that reached NE safety limit will proceed directly to echo.
Patients that correct CRT with first tier interventions will not be subjected to obligatory echo but will just proceed to periodic monitoring. Receives: Other: Usual care (UC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
A composite of all cause 28-days mortality plus time to cessation of vital support and length of hospital stay
A hierarchical composite of all cause mortality within 28 days, time to cessation of vital support (truncated at 28 days) and length of hospital stay (truncated at 28 days).
Measured: 28 days
Secondary outcomes (3)
All-cause mortality within 28 days
All-cause mortality within 28 days
Measured: 28 days
Vital support free days
The number of calendar days between randomization and 28 days that the patient is alive and with no requirement of cardiovascular, respiratory and renal support. Patients who die within 28 days will have zero days counted for this variable, irrespective of vital support status.
Resolution of cardiovascular failure implies complete stopping of vasopressor support for at least 24 consecutive hours. Resolution of respiratory failure implies extubation / liberation from mechanical ventilation for at least 48 hours. Resolution of renal failure implies liberation of renal replacement therapy for at least 72 hours in those receiving continuous replacement modalities and at least 5 days for those receiving intermittent ones.
Measured: 28 days
Length of hospital stay
Number of days remaining hospitalized (from randomization up to hospital discharge), truncated at day 28.
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 posted2 Oct 2023
- Study start6 Feb 2024
- Primary completion1 Dec 2025 (estimated)
- Study completion30 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intensive Care Unit Acquired WeaknessStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- comparative multicentre, open-label, investigator-led randomized controlled trial.
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06062303
- Sponsor's protocol ID
- APHP220794
- Acronym
- ANDROMEDA-FR
- Status last verified
- Nov 2024
- First submitted
- 25 Sep 2023
- Last updated
- 5 Dec 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hemodynamic Phenotype-Based, Capillary Refill Time-Targeted Resuscitation In Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial (A2)
- ClinicalTrials.gov ID
- NCT06062303
- Acronym / sponsor ID
- ANDROMEDA-FR / APHP220794
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 6 Feb 2024 (actual)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 30 May 2026 (estimated)
- First posted
- 2 Oct 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.
Over-resuscitation including fluid overload has been associated with increased morbidity (prolonged duration of organ failure) and mortality in septic shock. "One-size-fits-all" resuscitation strategies may increase septic shock mortality. However, clinical studies on individualized resuscitation are lacking. Hemodynamic phenotyping may allow to individualize septic shock resuscitation. The ANDROMEDA-SHOCK trial found that a simple clinical and bedside CRT-targeted resuscitation reduces organ dysfunction and 28-day mortality in septic shock. The current study will examine the hypothesis that a CRT-targeted resuscitation based on hemodynamic phenotyping considering within an decision tree usual bedside clinical parameters such as pulse pressure, diastolic blood pressure, fluid responsiveness and cardiac performance can further decrease mortality in septic shock as compared to usual care.
Detailed description
Septic shock is associated with a high mortality risk related to progressive tissue hypoperfusion.However, despite extensive research on the best monitoring and resuscitation strategies, many uncertainties remain. Over-resuscitation, particularly when inducing fluid overload, might contribute to a worse outcome. Fluid overload more likely occurs when fluids are administered to fluid unresponsive patients, but also when inappropriate resuscitation goals are pursued, or a "one-size-fit all" strategy is followed. From a hemodynamic point of view, several pathogenic mechanisms determine a progressive circulatory dysfunction While loss of vascular tone and relative hypovolemia predominate in early phases, more complex mechanisms such as endothelial and microcirculatory dysfunction, progressive vasoplegia, and myocardial dysfunction may be involved later. In effect, from a clinical point of view, many patients despite been fluid loaded in pre-intensive care unit settings, are still evidently hypovolemic and benefit from further administration of fluid boluses. Others, however, present very low diastolic arterial pressures reflecting profound vasoplegia, and recent data suggest that these patients may benefit from early norepinephrine instead of fluids[; on the contrary, administering fluids may fail to correct vascular tone and increase the risk of fluid overload[2]. In addition, a recent echocardiography-based study confirms that a relevant myocardial dysfunction is present in a significant number of patients, and that several cardiovascular phenotypes with a potentially different therapeutic approach may be recognized[8]. Unfortunately, despite the availability of most of the parameters at the bedside and research efforts, no universally applicable clinical phenotyping method for septic shock patients has been translated to usual practice. This is particularly problematic since chocardiography is not immediately available in the majority of centers worldwide, and therefore initial decisions on fluid resuscitation are usually based on clinical grounds and tend to follow the one-size-fits-all principle, leading to the risk of fluid overload.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- comparative multicentre, open-label, investigator-led randomized controlled trial.
| Arm | Type | Receives |
|---|---|---|
| Compartor arm | No intervention | –- Patients allocated to the usual care group will be managed by the clinical staff according to usual practice at their sites including decisions about hemodynamic and perfusion monitoring, and all treatments, but should follow general recommendations of the Surviving Sepsis Campaign to avoid extremes of clinical practice. This includes basic hemodynamic targets such as a MAP >65 mmHg, HR (heart rate) <120 beats per minute (BPM), arterial oxygen saturation (SaO2) >94%, Hb > 7 gr/dl, and the use of NE as the first vasopressor and crystalloids as the fluid of choice. |
| Capillary-refill time and phenotyping group | Active comparator | Other: Usual care (UC)Patients w/normal baseline CRT will be periodically monitored. Patients with abnormal CRT and septic shock will be categorized according to pulse pressure (PP). If <40 mmHg, will go to fluid responsiveness (FR) assessment. FR (-) patients will undergo cardiac echo to rule out significant dysfunction. Fluid boluses will be administered in 30 min intervals and repeated as needed if CRT is still abnormal. Patients with PP ≥40 mmHg will proceed according to diastolic pressure (DAP). If ≥50 mmHg will move to FR assessment. If <50 mmHg NE will be increased for MAP >65 mmHg and DAP ≥50 mmHg w/CRT assessed 1 h after. NE will be increased in 0.1 mcg/k/m increments up to 0.5 mcg/k/m. If CRT is normal, patients will proceed to periodic monitoring. Patients with persistent abnormal CRT or that reached NE safety limit will proceed directly to echo. Patients that correct CRT with first tier interventions will not be subjected to obligatory echo but will just proceed to periodic monitoring. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Consecutive adult patients (≥ 18 years)
- Patients with septic shock according to Sepsis-3 consensus conference. In short, septic shock is defined as suspected or confirmed infection, plus hyperlactatemia and NE requirements due to persistent hypotension, after a fluid load of at least 1000mL in 1h
- Patient and/or relative informed and having signed the information and consent form for participation in the study
Key exclusion criteria (15 listed)
- More than 4 hours since septic shock diagnosis,
- Anticipated surgery or acute hemodialysis procedure to start during the 6h intervention period
- Active bleeding,
- Do not resuscitate status,
- Child B-C Cirrhosis
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 |
|---|---|---|
| Usual care (UC)- Patients allocated to the UC group will be managed by the clinical staff according to usual practice at their sites including decisions about hemodynamic and perfusion monitoring, and all treatments, but should follow general recommendations of the Surviving Sepsis Campaign to avoid extremes of clinical practice. This includes basic hemodynamic targets such as a MAP >65 mmHg, heart rate (HR) <120 beats per minute (BPM), arterial oxygen saturation (SaO2) >94%, Hb > 7 gr/dl, and the use of NE as the first vasopressor and crystalloids as the fluid of choice. | Other | Capillary-refill time and phenotyping group |
Primary outcome
A composite of all cause 28-days mortality plus time to cessation of vital support and length of hospital stay
Time frame: 28 days
A hierarchical composite of all cause mortality within 28 days, time to cessation of vital support (truncated at 28 days) and length of hospital stay (truncated at 28 days).
3 secondary outcomes
All-cause mortality within 28 days
Time frame: 28 days
Vital support free days
Time frame: 28 days
Length of hospital stay
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 5 Dec 2024.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Intensive Care Unit Acquired Weakness and Shock, Septic, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 15 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 5 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 France. 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?
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 Olfa MD Hamzaoui, PhD (0033310736973, ohamzaoui@chu-reims.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A composite of all cause 28-days mortality plus time to cessation of vital support and length of hospital stay (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2024.