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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04411472




Registration number
NCT04411472
Ethics application status
Date submitted
28/05/2020
Date registered
2/06/2020
Date last updated
3/06/2024

Titles & IDs
Public title
(Revival) Study to Investigate the Efficacy and Safety of Alkaline Phosphatase in Patients With Sepsis-Associated AKI
Scientific title
A DB, Placebo-Controlled, Two-Arm Parallel-Group, Phase 3 RCT to Investigate the Efficacy and Safety of Recombinant Human Alkaline Phosphatase for Treatment of Patients With SA-AKI
Secondary ID [1] 0 0
AP-recAP-AKI-03-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Kidney Injury Due to Sepsis 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Renal and Urogenital 0 0 0 0
Kidney disease
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Recombinant human alkaline phosphatase
Other interventions - Placebo

Experimental: active - recombinant human alkaline phosphatase 1.6mg/kg 3 daily 1 hour infusions

Placebo comparator: placebo - matching placebo


Treatment: Other: Recombinant human alkaline phosphatase
patients with SA-AKI are randomly assigned in a 1:1 ratio to either placebo or 1.6 mg/kg recAP.

Other interventions: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
28-day All-cause Mortality: Main Trial Population
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
28-day All-cause Mortality: Moderate Chronic Kidney Disease Population
Timepoint [2] 0 0
28 days
Primary outcome [3] 0 0
28-day All-cause Mortality: COVID-19 Population
Timepoint [3] 0 0
28 days
Secondary outcome [1] 0 0
Major Adverse Kidney Events 90: Main Trial Population
Timepoint [1] 0 0
90 Days
Secondary outcome [2] 0 0
Major Adverse Kidney Events 90: Moderate Chronic Kidney Disease Population
Timepoint [2] 0 0
90 Days
Secondary outcome [3] 0 0
Major Adverse Kidney Events 90: COVID-19 Population
Timepoint [3] 0 0
90 Days
Secondary outcome [4] 0 0
Major Adverse Kidney Events Through Day 90: Combined Population
Timepoint [4] 0 0
90 Days
Secondary outcome [5] 0 0
Days Alive and Free of Organ Support Through Day 28: Main Trial Population
Timepoint [5] 0 0
28 days
Secondary outcome [6] 0 0
Days Alive and Free of Organ Support Through Day 28: Moderate Chronic Kidney Disease Population
Timepoint [6] 0 0
28 days
Secondary outcome [7] 0 0
Days Alive and Free of Organ Support Through Day 28: COVID-19 Population
Timepoint [7] 0 0
28 days
Secondary outcome [8] 0 0
Days Alive and Out of the ICU Through Day 28: Main Trial Population
Timepoint [8] 0 0
28 days
Secondary outcome [9] 0 0
Days Alive and Out of the ICU Through Day 28: Moderate Chronic Kidney Disease Population
Timepoint [9] 0 0
28 days
Secondary outcome [10] 0 0
Days Alive and Out of the ICU Through Day 28: COVID-19 Population
Timepoint [10] 0 0
28 days
Secondary outcome [11] 0 0
90-day All Cause Mortality: Main Trial Population
Timepoint [11] 0 0
90 days
Secondary outcome [12] 0 0
90-day All Cause Mortality: Moderate Chronic Kidney Disease Population
Timepoint [12] 0 0
90 days
Secondary outcome [13] 0 0
90-day All Cause Mortality: COVID-19 Population
Timepoint [13] 0 0
90 days

Eligibility
Key inclusion criteria
1. 18 years or older.
2. In the ICU or intermediate care unit for clinical reasons.
3. Have sepsis requiring vasopressor (norepinephrine, epinephrine, dopamine, phenylephrine, vasopressin, or angiotensin II) therapy, i.e.:

1. suspected or proven bacterial or viral infection. and
2. on vasopressor therapy (=0.1 µg/kg/min norepinephrine or equivalent) for sepsis-induced hypotension for at least one hour despite adequate fluid resuscitation according to clinical judgement. Following the initial one hour on at least 0.1 µg/kg/min norepinephrine or equivalent, any dose of vasopressor counts as vasopressor therapy.

The combination of a) and b) automatically ensures that patients fulfill the Sepsis 3 criteria as 0.1 µg/kg/min norepinephrine corresponds to a score of +4 on the Cardiovascular sub-score of the SOFA score.
4. Have AKI according to at least one of the below KDIGO criteria, a to d:

1. An absolute increase in serum or plasma creatinine (CR) by =0.3 mg/dL (=26.5 µmol/L) within 48 hours.

or
2. A relative increase in CR to =1.5 times the pre-AKI reference CR value which is known or presumed to have occurred within prior 7 days.

or
3. A decrease in urinary output to <0.5 mL/kg/hour for a minimum of 6 hours following adequate fluid resuscitation.

or d) If the patient does not have a known history of CKD and there is no pre-AKI reference CR value available from the past 12 months available from the past 12 months: a CR value greater or equal to the levels presented in Table 1, with the increase in CR presumed to have occurred within prior 7 days.
5. Provision of signed and dated ICF in accordance with local regulations.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. a) At sites where enrolment of 'moderate' CKD patients is allowed, patients with 'severe' CKD defined as a pre-AKI reference eGFR <25 mL/min/1.73 m2 are excluded.

* For patients with known CKD, the most recent eGFR prior to index hospitalization needs to be documented as =25 mL/min/1.73 m2.
* For patients with known CKD but no known eGFR prior to hospitalization, presentation eGFR between 25-60 mL/min/1.73 m2 can also be used to rule out 'severe' CKD.

b) At sites where enrolment of 'moderate' CKD patients is NOT allowed, patients with 'moderate' and 'severe' CKD defined as a pre-AKI reference eGFR <45 mL/min/1.73 m2 are excluded.
* For patients with known CKD, the most recent eGFR prior to index hospitalization needs to be documented as =45 mL/min/1.73 m2.
* For patients with known CKD but no known eGFR prior to hospitalization, presentation eGFR between 45-60 mL/min/1.73 m2 can also be used to rule out 'moderate' and 'severe' CKD.
2. Advanced chronic liver disease, defined as a Child-Pugh score of 10 to 15 (Class C).
3. Acute pancreatitis without proven infection.
4. Urosepsis related to suspected or proven urinary tract obstruction.
5. Main cause of AKI not sepsis.
6. Proven or suspected SARS-CoV-2 infection. NOTE: This exclusion criterion does not apply to patients in the COVID-19 population, in which COVID-19 should be the main cause of SA-AKI.
7. Severe burns requiring ICU treatment.
8. Severely immunosuppressed, e.g. due to:

* hematopoietic cell transplantation within past 6 months prior to Screening or acute or chronic graft-versus-host disease
* solid organ transplantation
* leukopenia not related to sepsis, i.e., preceding sepsis
* Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS)
* receiving chemotherapy within 30 days prior to Screening.
9. At high risk of being LTFU, e.g., due to known current or recent (within the last 6 months) IV drug abuse or known to be homeless.
10. Limitations to use of mechanical ventilation (MV), RRT or vasopressors and inotropes (NOTE: limitation of cardiopulmonary resuscitation (CPR) only is not an exclusion criterion).
11. Previous administration of recAP.
12. Use of a non-marketed drug within the last month or concurrent or planned participation in a clinical trial for a non-marketed drug or device. (NOTE: Co-enrollment or concurrent participation in observational, non-interventional trials using no protocolized treatments or procedures are always allowed. Co-enrollment or concurrent participation in trials using protocolized treatments or procedures, e.g. blood draws, requires pre-approval by the TSC).
13. Current or planned extracorporeal membrane oxygenation (ECMO).
14. On RRT >24 hours before start of trial drug.
15. No longer on vasopressor therapy at time of randomization.
16. On continuous vasopressor therapy for >72 hours before start of trial drug.
17. Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 based on the most recent available CR sample at time of screening (NOTE: will often be the sample used to diagnose AKI). eGFR should be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. In Japan, the CKD-EPI formula with Japanese coefficient should be used. If local regulations prohibit correcting for race in the calculation of eGFR, it is acceptable to use the formula without correcting for race.
18. Not feasible to start trial drug within:

1. 48 hours from AKI diagnosis, when AKI diagnosis precedes start of vasopressor therapy.

or
2. 24 hours from AKI diagnosis, when AKI is diagnosed after start of vasopressor therapy.
19. Pregnant or nursing women.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/08/2022
Sample size
Target
Accrual to date
Final
676
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
Bendigo Hospital - Bendigo
Recruitment hospital [3] 0 0
Footscray Hospital - Footscray
Recruitment hospital [4] 0 0
Austin Hospital - Melbourne
Recruitment hospital [5] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [6] 0 0
Sunshine Hospital ICU - Western Hospital - Saint Albans
Recruitment hospital [7] 0 0
Gold Coast University Hospital (GCUH) - Southport
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
3550 - Bendigo
Recruitment postcode(s) [3] 0 0
3011 - Footscray
Recruitment postcode(s) [4] 0 0
3084 - Melbourne
Recruitment postcode(s) [5] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [6] 0 0
3021 - Saint Albans
Recruitment postcode(s) [7] 0 0
4215 - Southport
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
California
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United States of America
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District of Columbia
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United States of America
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Georgia
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United States of America
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Illinois
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Kentucky
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Minnesota
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New Mexico
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North Carolina
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Ohio
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Pennsylvania
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Virginia
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United States of America
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Wisconsin
Country [14] 0 0
Austria
State/province [14] 0 0
Graz
Country [15] 0 0
Austria
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Innsbruck
Country [16] 0 0
Belgium
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Brussels
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Belgium
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Charleroi
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Belgium
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Genk
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Belgium
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Gent
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Jette
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La Louvière
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Ottignies
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Woluwe-Saint-Lambert
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Yvoir
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Aalborg
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Kumamoto-Shi
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Omihachiman-Shi
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Osaka-Shi
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Osaka-shi
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Toyoake-Shi
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Yokohama-Shi
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NB
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Amsterdam
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Ede
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Enschede
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Heerlen
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Nijmegen
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WGN
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Auckland
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Christchurch
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Grafton
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Hastings
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Girona
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Sabadell
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Liverpool
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London
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Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AM-Pharma
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
A Legters
Address 0 0
AM-Pharma
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents


Results not provided in https://clinicaltrials.gov/study/NCT04411472