Trial Outcomes & Findings for Is Adrenal Insufficiency Under-diagnosed in Hospitalized Cirrhosis Patients? (NCT NCT03368066)

NCT ID: NCT03368066

Last Updated: 2021-12-09

Results Overview

A percent quantification of serum cholesterol esterification will be measured via blood draw. Low values represent deficiency in esterification, which is a surrogate measure of lecthicin-cholesterol acetyltransferase (LCAT) enzymatic deficiency.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 100 participants
• Primary outcome timeframe: 24 hours
• Results posted on: 2021-12-09

Participant Flow

5 patients were excluded - 1 patient did not undergo cortisol stimulation testing due to administrative error and 4 patients had compensated cirrhosis (Child Pugh A).

Participant milestones

Measure	Normal Adrenal Response Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Overall Study STARTED	58	37
Overall Study COMPLETED	58	37
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	Hospitalized Cirrhosis Patients n=95 Participants Administration of cortisol stimulation test to assess for presence or absence of adrenal insufficiency Cosyntropin: Administer 250mcg cosyntropin to hospitalized cirrhosis patients to assess for the presence of adrenal insufficiency
Age, Continuous	58 years n=95 Participants
Sex: Female, Male Female	39 Participants n=95 Participants
Sex: Female, Male Male	56 Participants n=95 Participants
Region of Enrollment United States	95 Participants n=95 Participants
Etiology of Cirrhosis Alcohol	33 Participants n=95 Participants
Etiology of Cirrhosis Non-alcoholic steatohepatitis	22 Participants n=95 Participants
Etiology of Cirrhosis Hepatitis C	9 Participants n=95 Participants
Etiology of Cirrhosis Cryptogenic	14 Participants n=95 Participants
Etiology of Cirrhosis Other	17 Participants n=95 Participants
Decompensation Ascites	88 Participants n=95 Participants
Decompensation Hepatic Encephalopathy	55 Participants n=95 Participants
Decompensation Esophageal Varices	68 Participants n=95 Participants
Hepatocellular Carcinoma	11 Participants n=95 Participants
Aldosterone Antagonist Use	55 Participants n=95 Participants
Beta Blocker Use	38 Participants n=95 Participants
Midodrine Use	6 Participants n=95 Participants
Infection During Hospitalization	24 Participants n=95 Participants
Intensive Care Unit Stay During Hospitalization	8 Participants n=95 Participants
Acute Kidney Injury (AKI) Stage 1	24 Participants n=95 Participants
Acute Kidney Injury (AKI) Stage 2	2 Participants n=95 Participants
Acute Kidney Injury (AKI) Stage 3	4 Participants n=95 Participants
Mean Arterial Pressure	78 mmHg n=95 Participants
Sodium	136 mEq/L n=95 Participants
Potassium	3.9 mEq/L n=95 Participants
Model for End-Stage Liver Disease (MELD) score	17 units on a scale n=95 Participants
Child Pugh classification B	51 Participants n=95 Participants
Child Pugh classification C	44 Participants n=95 Participants
Albumin	2.8 g/dL n=95 Participants
HDL	23 mg/dL n=95 Participants
Baseline Cortisol	7.9 micrograms/dL n=95 Participants
Delta Cortisol	10.0 micrograms/dL n=95 Participants
Free Cortisol	0.6 micrograms/dL n=95 Participants
Cortisol Binding Globulin	1.7 mg/dL n=95 Participants
Cholesterol Esters	66 percentage of esterified cholesterol n=95 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: 2 patients in normal adrenal response group and 3 patients in RAI group were missing cholesterol ester percentage measurements

A percent quantification of serum cholesterol esterification will be measured via blood draw. Low values represent deficiency in esterification, which is a surrogate measure of lecthicin-cholesterol acetyltransferase (LCAT) enzymatic deficiency.

Outcome measures

Measure	Normal Adrenal Response n=56 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency n=34 Participants Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Number of Participants With Cholesterol Esterification Deficiency	10 Participants	11 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: 2 patients with RAI were missing peripheral smears to assess for the presence of spur cells

A peripheral blood smear will be obtained and assessed for presence of acanthocytes (spur cells). Spur cell anemia is defined as a serum hemoglobin < 10g/dL and the presence of >= 5% spur cells on blood smear.

Outcome measures

Measure	Normal Adrenal Response n=58 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency n=35 Participants Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Number of Participants With Spur Cell Anemia	6 Participants	8 Participants

PRIMARY outcome

Timeframe: 6 months

Transplant and Death are considered equivalent outcomes

Outcome measures

Measure	Normal Adrenal Response n=58 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency n=37 Participants Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Participant Transplant-Free Survival	41 Participants	16 Participants

SECONDARY outcome

Timeframe: 24 hours

A baseline total cortisol level will be obtained and then patients will receive a standard-dose synthetic ACTH (250mcg of Cosyntropin) stimulation test to assess for the presence of adrenal insufficiency. RAI is defined as a change in the total cortisol level in response to the stimulation test of <9mcg/dL when measured 60 minutes after the Cosyntropin is administered.

Outcome measures

Measure	Normal Adrenal Response n=95 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Number of Participants With Relative Adrenal Insufficiency (RAI)	37 Participants	—

SECONDARY outcome

Timeframe: 24 hours

Population: 1 patient from normal adrenal response group was missing free cortisol data

Patients will have their free cortisol levels measured to assess for deficiency.

Outcome measures

Measure	Normal Adrenal Response n=57 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency n=37 Participants Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Number of Participants With Low Free Cortisol	6 Participants	1 Participants

SECONDARY outcome

Timeframe: 90 days

Patients who received a liver transplant within 90 days of enrollment

Outcome measures

Measure	Normal Adrenal Response n=58 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency n=37 Participants Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Number of Participants Who Received Liver Transplantation at 90 Days	6 Participants	5 Participants

SECONDARY outcome

Timeframe: 6 months

Patients who received a liver transplant within 6 months of enrollment

Outcome measures

Measure	Normal Adrenal Response n=58 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency n=37 Participants Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Number of Participants Who Received Liver Transplantation at 6 Months	8 Participants	6 Participants

SECONDARY outcome

Timeframe: Within Hospitalization

Patients who died within the same hospitalization as enrollment

Outcome measures

Measure	Normal Adrenal Response n=58 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency n=37 Participants Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Number of Participants Who Died Within Index Hospitalization	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 30 days

Patients who died within 30 days of enrollment

Outcome measures

Measure	Normal Adrenal Response n=58 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency n=37 Participants Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Number of Participants Who Died at 30 Days	4 Participants	4 Participants

SECONDARY outcome

Timeframe: 90 days

Patients who died within 90 days of enrollment

Outcome measures

Measure	Normal Adrenal Response n=58 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency n=37 Participants Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Number of Participants Who Died at 90 Days	5 Participants	12 Participants

SECONDARY outcome

Timeframe: 6 months

Patients who died within 6 months of enrollment

Outcome measures

Measure	Normal Adrenal Response n=58 Participants Delta cortisol response to 250mcg Cosyntropin \> 9 micrograms/dL	Relative Adrenal Insufficiency n=37 Participants Delta cortisol response to 250mcg Cosyntropin \< 9 micrograms/dL
Number of Participants Who Died at 6 Months	9 Participants	15 Participants

Adverse Events

Hospitalized Cirrhosis Patients

Serious events: 25 serious events

Other events: 1 other events

Deaths: 25 deaths

Serious adverse events

Measure	Hospitalized Cirrhosis Patients n=100 participants at risk Administration of cortisol stimulation test to assess for presence or absence of adrenal insufficiency Cosyntropin: Administer 250mcg cosyntropin to hospitalized cirrhosis patients to assess for the presence of adrenal insufficiency
Hepatobiliary disorders Liver-related death	24.0% 24/100 • Number of events 24 • 6 months
General disorders Non-liver-related death	1.0% 1/100 • Number of events 1 • 6 months

Other adverse events

Measure	Hospitalized Cirrhosis Patients n=100 participants at risk Administration of cortisol stimulation test to assess for presence or absence of adrenal insufficiency Cosyntropin: Administer 250mcg cosyntropin to hospitalized cirrhosis patients to assess for the presence of adrenal insufficiency
Gastrointestinal disorders Nausea	1.0% 1/100 • Number of events 1 • 6 months

Additional Information

Dr. Brian Wentworth

University of Virginia

Phone: 9739436781

Email: bw8xz@hscmail.mcc.virginia.edu

Results disclosure agreements

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