Trial Outcomes & Findings for Safety Study of Kedbumin 25% Versus Normal Saline in the Treatment of Post-Surgical Hypovolemia in Pediatric Patients (NCT NCT01531803)

NCT ID: NCT01531803

Last Updated: 2023-11-15

Results Overview

Criteria for Primary Evaluation: 1. Presence of rales at pulmonary bases: cut-off YES/NO and at least one of the following: * Chest X Ray: presence of Kerley B lines: cut-off YES/NO; * Doppler sonography to measure the pulmonary artery pressure: cut-off \>20mmHg; * Arterial oxygen saturation: cut-off ≤ 90% and/or ABG: cut-off pO2 ≤ 70mmHg. 2. Fluid overload and edema is quantified by % increase in body weight over the subject's preoperative weight stratified by \<10%, 11-15%, 16-20% and \>20%. 3. Physical examination for edema. All the measurements for the assessment of the safety parameters will be collected, reviewed, and recorded by research staff until hemodynamic stability is achieved.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 3 participants
• Primary outcome timeframe: 3 days
• Results posted on: 2023-11-15

Participant Flow

Participant milestones

Measure	Kedbumin 25% Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g/L human albumin, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin). The duration of treatment is based on the subject's response to treatment until hemodynamic stability is achieved. If hemodynamic stability is not achieved within 72 hours of starting the study treatment, the subject will be withdrawn from the study and will be treated according to standard practice and data collected during the study period will be used for the safety evaluation. Kedbumin 25%: Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g human albumin /L, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin).	Normal Saline Solution Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment. Normal Saline Solution: Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment.
Overall Study STARTED	1	2
Overall Study COMPLETED	1	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety Study of Kedbumin 25% Versus Normal Saline in the Treatment of Post-Surgical Hypovolemia in Pediatric Patients

Baseline characteristics by cohort

Measure	Kedbumin 25% n=1 Participants Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g/L human albumin, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin). The duration of treatment is based on the subject's response to treatment until hemodynamic stability is achieved. If hemodynamic stability is not achieved within 72 hours of starting the study treatment, the subject will be withdrawn from the study and will be treated according to standard practice and data collected during the study period will be used for the safety evaluation. Kedbumin 25%: Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g human albumin /L, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin).	Normal Saline Solution n=2 Participants Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment. Normal Saline Solution: Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment.	Total n=3 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 days

Population: The study has been prematurely stopped.

Criteria for Primary Evaluation:

1. Presence of rales at pulmonary bases: cut-off YES/NO and at least one of the following:

• Chest X Ray: presence of Kerley B lines: cut-off YES/NO;
• Doppler sonography to measure the pulmonary artery pressure: cut-off >20mmHg;
• Arterial oxygen saturation: cut-off ≤ 90% and/or ABG: cut-off pO2 ≤ 70mmHg.

2. Fluid overload and edema is quantified by % increase in body weight over the subject's preoperative weight stratified by <10%, 11-15%, 16-20% and >20%.

3. Physical examination for edema.

All the measurements for the assessment of the safety parameters will be collected, reviewed, and recorded by research staff until hemodynamic stability is achieved.

Outcome measures

Measure	Kedbumin 25% n=1 Participants Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g/L human albumin, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin). The duration of treatment is based on the subject's response to treatment until hemodynamic stability is achieved. If hemodynamic stability is not achieved within 72 hours of starting the study treatment, the subject will be withdrawn from the study and will be treated according to standard practice and data collected during the study period will be used for the safety evaluation. Kedbumin 25%: Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g human albumin /L, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin).	Normal Saline Solution n=2 Participants Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment. Normal Saline Solution: Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment.
Incidence, Severity, and Seriousness of Fluid Overload and Edema (Pulmonary Portal or Systemic) and/or Other Complications Secondary to Fluid Resuscitation With Kedbumin 25% Compared to Normal Saline.	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 3 days

Population: The study has been prematurely stopped.

The secondary safety parameter of resolution of hypovolemia and adequate fluid resuscitation will be evaluated based on the following indicators:

• Hemodynamic status [heart rate (HR), blood pressure (BP), urine output (UOP)];
• Tissue hypoperfusion [lactate levels, base deficit derived from arterial blood gas, if arterial line is in place] or determined by the use of a pulse oximetry;
• Electrolyte status [Na+, Ca++, Mg++, K+, Cl- ,PO4];
• Renal/hepatic function [urine albumin, blood urea nitrogen (BUN), creatinine, creatinine clearance, total bilirubin, ALT, AST, Albumin, Alkaline Phosphatase (ALP), gamma glutamyltransferase (GGT)];
• Complete blood count (CBC);
• Partial Thromboplastin Time/ International Normalized Ratio (PTT/INR).

All the measurements for the assessment of the safety parameters will be collected, reviewed, and recorded by research staff until hemodynamic stability is achieved.

Outcome measures

Measure	Kedbumin 25% n=1 Participants Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g/L human albumin, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin). The duration of treatment is based on the subject's response to treatment until hemodynamic stability is achieved. If hemodynamic stability is not achieved within 72 hours of starting the study treatment, the subject will be withdrawn from the study and will be treated according to standard practice and data collected during the study period will be used for the safety evaluation. Kedbumin 25%: Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g human albumin /L, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin).	Normal Saline Solution n=2 Participants Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment. Normal Saline Solution: Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment.
Resolution of Hypovolemia With Adequate Fluid Resuscitation and Restoration of Hemodynamic Stability After Treatment With Kedbumin 25% Compared to Normal Saline Within 72 Hours.	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 30 days

Population: The study has been prematurely stopped. Only 3 participants have been enrolled and one of them showed a non-serious adverse event (AE) of superficial wound infection of mild intensity not related to the study drug.

The severity, seriousness, and relatedness of AEs to the study drug will be observed on repeated administrations of the study drug.

Subjects will be carefully monitored by the SICU/NICU/PICU or acute care floor staff for expected and unexpected AEs which occur from the time of dosing to 30 days post dose.

If the subject is discharged prior to 30 days, research staff will collect AEs at follow-up visits and via spontaneous reporting by the subject.

Outcome measures

Measure	Kedbumin 25% n=1 Participants Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g/L human albumin, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin). The duration of treatment is based on the subject's response to treatment until hemodynamic stability is achieved. If hemodynamic stability is not achieved within 72 hours of starting the study treatment, the subject will be withdrawn from the study and will be treated according to standard practice and data collected during the study period will be used for the safety evaluation. Kedbumin 25%: Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g human albumin /L, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin).	Normal Saline Solution n=2 Participants Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment. Normal Saline Solution: Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment.
Incidence, Severity and Seriousness of Expected and Unexpected AEs After Treatment With Kedbumin 25% Compared to Normal Saline.	0 Participants	1 Participants

Adverse Events

Kedbumin 25%

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Normal Saline Solution

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Kedbumin 25% n=1 participants at risk Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g/L human albumin, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin). The duration of treatment is based on the subject's response to treatment until hemodynamic stability is achieved. If hemodynamic stability is not achieved within 72 hours of starting the study treatment, the subject will be withdrawn from the study and will be treated according to standard practice and data collected during the study period will be used for the safety evaluation. Kedbumin 25%: Albumin (Human) 25% solution for intravenous (IV) infusion in the dosage strength of 250g human albumin /L, supplied in 50 mL type II vial (each vial containing 12.5g human albumin). The dose will be 0.5 to 1g/kg body weight (2 to 4 mL/kg of 25% albumin).	Normal Saline Solution n=2 participants at risk Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment. Normal Saline Solution: Normal (0.9%) saline solution administered via IV infusions of 10 to 20 mL/kg as appropriate per standard of care based on the subject's clinical status and response to treatment.
Skin and subcutaneous tissue disorders Superficial Wound Infection	0.00% 0/1 • 30 days	50.0% 1/2 • Number of events 1 • 30 days

Additional Information

Dr. Mirella Calcinai, MD, Clinical Research Director

Kedrion S.p.A

Phone: +393486559761

Email: m.calcinai@kedrion.com

Results disclosure agreements

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