Trial Outcomes & Findings for Albumin Replacement Therapy in Septic Shock (NCT NCT03869385)

NCT ID: NCT03869385

Last Updated: 2024-10-28

Results Overview

Mortality within 90 days after randomisation

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 440 participants
• Primary outcome timeframe: 90 days
• Results posted on: 2024-10-28

Participant Flow

Participant milestones

Measure	Albumin Group Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
Overall Study STARTED	222	218
Overall Study COMPLETED	222	218
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Albumin Group n=222 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=218 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. The demographic and baseline characteristics were similar between the study groups.	Total n=440 Participants Total of all reporting groups
Age, Continuous	69.5 years n=222 Participants	68.5 years n=218 Participants	69 years n=440 Participants
Sex: Female, Male Female	80 Participants n=222 Participants	70 Participants n=218 Participants	150 Participants n=440 Participants
Sex: Female, Male Male	142 Participants n=222 Participants	148 Participants n=218 Participants	290 Participants n=440 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Germany	222 participants n=222 Participants	218 participants n=218 Participants	440 participants n=440 Participants
Blood lactate level	4.9 mmol/liter n=222 Participants	5 mmol/liter n=218 Participants	4.9 mmol/liter n=440 Participants
Serum albumin	22 g/liter STANDARD_DEVIATION 6 • n=222 Participants	22 g/liter STANDARD_DEVIATION 6 • n=218 Participants	22 g/liter STANDARD_DEVIATION 6 • n=440 Participants

PRIMARY outcome

Timeframe: 90 days

Population: Informed consents were not possible to obtain within 72 hours after randomization in 14 patients, 4 patients were lost to follow up, 2 patients withdrew the informed consent, and the study was terminated in one patient due to investigator decision. Therefore, the primary outcome parameter was available for analysis in 210 patients in the albumin and 209 patients in the control groups

Mortality within 90 days after randomisation

Outcome measures

Measure	Albumin Group n=210 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=209 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
90-day All Cause Mortality	91 Participants	96 Participants

SECONDARY outcome

Timeframe: 28 days

Population: At 28 days after randomization, informed consent was not possible to be obtained within 72 hours of randomization in 14 patients, 2 patients withdrew consent, and the study was terminated in one patient due to investigator decision. Therefore, 28-days mortality were available in 213 vs. 210 patients in the albumin vs. control group, respectively

Mortality within 28 days after randomisation

Outcome measures

Measure	Albumin Group n=213 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=210 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
28-day Mortality	66 Participants	80 Participants

SECONDARY outcome

Timeframe: 60 days

Population: At 60 days after randomization, informed consent was not possible to be obtained within 72 hours of randomization in 14 patients, 2 patients withdrew consent, 2 patients were lost to follow-up, and the study was terminated in one patient due to investigator decision. Therefore, 60-days mortality were available in 211 vs. 210 patients in the albumin vs. control group, respectively

Mortality within 60 days after randomisation

Outcome measures

Measure	Albumin Group n=211 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=210 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
60-day Mortality	82 Participants	95 Participants

SECONDARY outcome

Timeframe: 28 days

Organ failure defined as increase in the daily recorded Sequential organ Failure Assessement (SOFA) subscores; cardiovascular, respiratory, hematologic, hepatic, renal, neurologic (range 0-4 points each) from a value <2 to a value ≥ 2

Outcome measures

Measure	Albumin Group n=222 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=218 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
Organ Failure 1 organ failure	68 participants	52 participants
Organ Failure 2 organ failures	19 participants	14 participants
Organ Failure 3 organ failures	2 participants	7 participants
Organ Failure 4 organ failures	0 participants	1 participants

SECONDARY outcome

Timeframe: 28 days

The overall degree of organ dysfunction/failure assessed daily by the total Sequential Organ Failure Score (SOFA score: range 0-24 points), with higher scores indicating higher degree of overall organ dysfunction/failure).

Outcome measures

Measure	Albumin Group n=222 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=218 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
Sequential Organ Failure Assessement (SOFA) Score	9 Points Standard Deviation 0.5	8.6 Points Standard Deviation 0.7

SECONDARY outcome

Timeframe: 90 days

Intensive Care unit stay of first hospitalization after randomisation within 90 days

Outcome measures

Measure	Albumin Group n=222 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=218 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
ICU Length of Stay	13 Days Interval 7.0 to 22.0	12 Days Interval 7.0 to 29.0

SECONDARY outcome

Timeframe: 90 days

Hospital stay of first hospitalization after randomisation within 90 days

Outcome measures

Measure	Albumin Group n=222 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=218 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
Hospital Length of Stay	24 Days Interval 15.0 to 42.0	27 Days Interval 14.0 to 45.0

SECONDARY outcome

Timeframe: 28 days

Ventilation-free days within 28 days after randomisation

Outcome measures

Measure	Albumin Group n=222 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=218 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
Ventilation-free Days	4 Days Interval 1.0 to 7.0	3 Days Interval 0.0 to 7.0

SECONDARY outcome

Timeframe: 28 days

Vasopressor-free days within 28 days after randomisation

Outcome measures

Measure	Albumin Group n=222 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=218 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
Vasopressor-free Days	2.5 Days Interval 0.0 to 7.0	2 Days Interval 0.0 to 6.0

SECONDARY outcome

Timeframe: 28 days

Total amount of fluid of fluid administration and total fluid balance in the ICU within 28 days after randomisation

Outcome measures

Measure	Albumin Group n=222 Participants Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=218 Participants The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
Total Amount of Fluid of Fluid Administration and Total Fluid Balance in the ICU. Total fluid balance	234 ml/day Interval -491.0 to 1290.0	355 ml/day Interval -402.0 to 1576.0
Total Amount of Fluid of Fluid Administration and Total Fluid Balance in the ICU. Total amount of fluid adminstration	3200 ml/day Interval 2502.0 to 3544.0	3693 ml/day Interval 2540.0 to 4443.0

Adverse Events

Albumin Group

Serious events: 3 serious events

Other events: 183 other events

Deaths: 91 deaths

Control Group Without Albumin:

Serious events: 2 serious events

Other events: 176 other events

Deaths: 96 deaths

Serious adverse events

Measure	Albumin Group n=222 participants at risk Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=218 participants at risk The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
Cardiac disorders Hypervolemia	1.4% 3/222 • In the albumin group until 24 h after the last dose of the trial drug Iin the control group without albumin until day 28 after randomisation or until discharge from the ICU, if it occurs before day 28 after randomisation. In the event that adverse events are still "ongoing" after the above dates, they were tracked until maximum the end of data collection (Day 90). If they are "ongoing" on day 90, they were documented as "not recovered," "recovered with sequelae," or "unknown." Events plausibly explainable by sepsis were recorded in both groups as sepsis-related clinical events, but not as adverse events (AEs). Documentation of the sepsis-related clinical event as an AE occurs only if the examiner suspects a connection with the administration of the trial drug, which is therefore only possible in the albumin group. Clinically relevant worsening of a pre-existing disease not related to sepsis was considered and documented as an AE.	0.92% 2/218 • In the albumin group until 24 h after the last dose of the trial drug Iin the control group without albumin until day 28 after randomisation or until discharge from the ICU, if it occurs before day 28 after randomisation. In the event that adverse events are still "ongoing" after the above dates, they were tracked until maximum the end of data collection (Day 90). If they are "ongoing" on day 90, they were documented as "not recovered," "recovered with sequelae," or "unknown." Events plausibly explainable by sepsis were recorded in both groups as sepsis-related clinical events, but not as adverse events (AEs). Documentation of the sepsis-related clinical event as an AE occurs only if the examiner suspects a connection with the administration of the trial drug, which is therefore only possible in the albumin group. Clinically relevant worsening of a pre-existing disease not related to sepsis was considered and documented as an AE.

Other adverse events

Measure	Albumin Group n=222 participants at risk Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion.	Control Group Without Albumin: n=218 participants at risk The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
Vascular disorders Sepsis related, Cardiovascular events	82.4% 183/222 • In the albumin group until 24 h after the last dose of the trial drug Iin the control group without albumin until day 28 after randomisation or until discharge from the ICU, if it occurs before day 28 after randomisation. In the event that adverse events are still "ongoing" after the above dates, they were tracked until maximum the end of data collection (Day 90). If they are "ongoing" on day 90, they were documented as "not recovered," "recovered with sequelae," or "unknown." Events plausibly explainable by sepsis were recorded in both groups as sepsis-related clinical events, but not as adverse events (AEs). Documentation of the sepsis-related clinical event as an AE occurs only if the examiner suspects a connection with the administration of the trial drug, which is therefore only possible in the albumin group. Clinically relevant worsening of a pre-existing disease not related to sepsis was considered and documented as an AE.	80.7% 176/218 • In the albumin group until 24 h after the last dose of the trial drug Iin the control group without albumin until day 28 after randomisation or until discharge from the ICU, if it occurs before day 28 after randomisation. In the event that adverse events are still "ongoing" after the above dates, they were tracked until maximum the end of data collection (Day 90). If they are "ongoing" on day 90, they were documented as "not recovered," "recovered with sequelae," or "unknown." Events plausibly explainable by sepsis were recorded in both groups as sepsis-related clinical events, but not as adverse events (AEs). Documentation of the sepsis-related clinical event as an AE occurs only if the examiner suspects a connection with the administration of the trial drug, which is therefore only possible in the albumin group. Clinically relevant worsening of a pre-existing disease not related to sepsis was considered and documented as an AE.

Additional Information

Prof. Dr. Yasser Sakr

University Hospital of Jena

Phone: 01742191538

Email: yasser.sakr@med.uni-jena.de

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place