Trial Outcomes & Findings for Lactic Acidosis During Entecavir(ETV)Treatment (NCT NCT01354652)

Last Updated: 2018-05-09

Results Overview

incidence of elevated venous lactate levels more than 2 mmol/L of any etiology until development of lactic acidosis, orthotropic liver transplantation (OLT), death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

5 participants

Primary outcome timeframe

participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Results posted on

2018-05-09

Participant Flow

Participant milestones

Participant milestones
Measure	Entecavir Oral 0.5mg/day until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18. Participants will be followed for the duration of hospital stay, an expected average of 8 weeks. entecavir, lamivudine: entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks. lamivudine: 100mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.	Lamivudine Oral 100mg/day lamivudine until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18. Participants will be followed for the duration of hospital stay, an expected average of 8 weeks. entecavir, lamivudine: entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks. lamivudine: 100mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.
Overall Study STARTED	3	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Lactic Acidosis During Entecavir(ETV)Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entecavir n=3 Participants Oral 0.5mg/day until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18. Participants will be followed for the duration of hospital stay, an expected average of 8 weeks. entecavir, lamivudine: entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks. lamivudine: 100mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.	Lamivudine n=2 Participants Oral 100mg/day lamivudine until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18. Participants will be followed for the duration of hospital stay, an expected average of 8 weeks. entecavir, lamivudine: entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks. lamivudine: 100mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.	no NRTI Group hepatitis C virus associated LC patients for the calculation of lactic acidosis incidence	Total n=5 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	—	5 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Age, Continuous	52.3 years STANDARD_DEVIATION 6.8 • n=5 Participants	38.0 years STANDARD_DEVIATION 7.1 • n=7 Participants	—	46.6 years STANDARD_DEVIATION 9.9 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	—	1 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	—	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	—	5 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	—	5 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Region of Enrollment Korea, Republic of	3 participants n=5 Participants	2 participants n=7 Participants	—	5 participants n=4 Participants

PRIMARY outcome

Timeframe: participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Population: Our study was terminated early with only 5 participant enrolled. We gained lactic acid levels for the 5 patients (all elevated), however we considered that it was not sufficient to be analyzed. Morover, we did not further investigate the etiology for elevated lactic acid levels and secondary etiology-based outcomes are not recorded here.

Outcome measures

Outcome measures
Measure	Entecavir n=3 Participants Oral 0.5mg/day until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18. Participants will be followed for the duration of hospital stay, an expected average of 8 weeks. entecavir, lamivudine: entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks. lamivudine: 100mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.	Lamivudine n=2 Participants Oral 100mg/day lamivudine until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18. Participants will be followed for the duration of hospital stay, an expected average of 8 weeks. entecavir, lamivudine: entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks. lamivudine: 100mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.	no NRTI Group hepatitis C virus associated LC patients for the calculation of lactic acidosis incidence
Incidence of Elevated Venous Lactate Levels More Than 2 mmol/L of Any Etiology	3 participants	2 participants	—

SECONDARY outcome

Timeframe: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Population: Secondary outcome assessment was not performed due to early termination of the study.

incidence of elevated venous lactate levels more than 2 mmol/L directly related to NRTI until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Population: Secondary outcome assessment was not performed due to early termination of the study.

incidence of elevated venous lactate levels more than 2 mmol/L caused by etiologies other than NTRIs until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Population: Secondary outcome assessment was not performed due to early termination of the study.

Frequency of concomitant prescribed medications possibly associated with lactic acidosis other than NTRIs until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Participants will be followed for the duration of hospital stay, an expected average of 8 weeks

Population: Secondary outcome assessment was not performed due to early termination of the study.

Arterial pH and anion gap in cases with elevated blood lactate levels (at the time of detection and peak levels until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Participants will be followed for the duration of hospital stay or outpatients visit, an expected average of 12 months

Overall OLT-free survival until development of OLT and death and participants will be followed for the duration of hospital stay or outpatients visit, an expected average of 12 months

Outcome measures

Outcome measures
Measure	Entecavir n=3 Participants Oral 0.5mg/day until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18. Participants will be followed for the duration of hospital stay, an expected average of 8 weeks. entecavir, lamivudine: entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks. lamivudine: 100mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.	Lamivudine n=2 Participants Oral 100mg/day lamivudine until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18. Participants will be followed for the duration of hospital stay, an expected average of 8 weeks. entecavir, lamivudine: entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks. lamivudine: 100mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.	no NRTI Group hepatitis C virus associated LC patients for the calculation of lactic acidosis incidence
Overall OLT-free Survival	411 day Standard Deviation 311	175 day Standard Deviation 223	—

Adverse Events

Entecavir

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Lamivudine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

no NRTI Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Han Chu Lee

AsanMC

Phone: 82230103915

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place