Trial Outcomes & Findings for Cryptococcal Antigen Screening Plus Sertraline (NCT NCT03002012)
NCT ID: NCT03002012
Last Updated: 2020-06-09
Results Overview
Cryptococcal meningitis free survival with retention-in-care through 6 months * Those who die of any cause are failures * Those developing symptomatic cryptococcal meningitis are failures * Those lost to follow up and unable to be tracked are considered failures
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
22 participants
Primary outcome timeframe
6 months
Results posted on
2020-06-09
Participant Flow
Participant milestones
| Measure |
Sertraline
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
11
|
|
Overall Study
COMPLETED
|
11
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cryptococcal Antigen Screening Plus Sertraline
Baseline characteristics by cohort
| Measure |
Sertraline
n=11 Participants
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 Participants
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
32 years
n=99 Participants
|
35 years
n=107 Participants
|
32 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
11 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Region of Enrollment
Uganda
|
11 participants
n=99 Participants
|
11 participants
n=107 Participants
|
22 participants
n=206 Participants
|
|
On Antiretroviral Therapy (ART) at Radomization
On ART
|
6 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
On Antiretroviral Therapy (ART) at Radomization
Not on ART
|
5 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
CD4 Cell Count
|
38 cells/mm3
n=99 Participants
|
50 cells/mm3
n=107 Participants
|
42 cells/mm3
n=206 Participants
|
PRIMARY outcome
Timeframe: 6 monthsCryptococcal meningitis free survival with retention-in-care through 6 months * Those who die of any cause are failures * Those developing symptomatic cryptococcal meningitis are failures * Those lost to follow up and unable to be tracked are considered failures
Outcome measures
| Measure |
Sertraline
n=11 Participants
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 Participants
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
6 Month Meningitis-free Survival
|
11 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: 6 monthsSurvival through 6 months
Outcome measures
| Measure |
Sertraline
n=11 Participants
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 Participants
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
6-month Survival
|
11 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: 6 monthsCumulative incidence of symptomatic cryptococcal meningoencephalitis through 6 months
Outcome measures
| Measure |
Sertraline
n=11 Participants
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 Participants
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
Cumulative Incidence of Symptomatic Cryptococcal Meningoencephalitis
|
0 meningitis events
|
1 meningitis events
|
SECONDARY outcome
Timeframe: 6 monthsNumber of Clinical Adverse Events by Division of AIDS (DAIDS) Scale for Grade 3-5 events through 6 months
Outcome measures
| Measure |
Sertraline
n=11 Participants
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 Participants
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
Number of Clinical Adverse Events (Grade 3-5)
|
4 number of grade 3-5 adverse events
|
2 number of grade 3-5 adverse events
|
SECONDARY outcome
Timeframe: 6 monthsNumber of Laboratory Grade 3-5 Adverse Events through 6 months as per the Division of AIDS (DAIDS) grading scale
Outcome measures
| Measure |
Sertraline
n=11 Participants
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 Participants
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
Number of Laboratory Grade 3-5 Adverse Events
|
4 number of grade 3-5 adverse events
|
1 number of grade 3-5 adverse events
|
SECONDARY outcome
Timeframe: 6 monthsNumber of participants whose study drug/placebo use was halted prematurely due to any cause through 6 months
Outcome measures
| Measure |
Sertraline
n=11 Participants
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 Participants
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
All-Cause Premature Study Drug/Placebo Discontinuation
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 12 weeksPrevalence of depression by Patient Health Questionnaire (PHQ-9) over 6 months as measured at baseline, 4 weeks, 8 weeks, and 12 weeks. The PHQ-9 is a 9-item instrument for screening, diagnosing, monitoring, and measuring the severity of depression. Items are rated on a scale from 0 (not at all) to 3 (nearly every day). Total score is a sum of 9 item scores (Range 0-27). Greater scores indicate greater depressive symptoms. PHQ-9 scores of: 0-4 Minimal/No depression; 5-9 Mild depression; 10-14 Moderate depression; 15-19 Moderate severe depression; 20-27 Severe depression. This endpoint reports the median (interquartile range) of the PHQ-9 scores over time.
Outcome measures
| Measure |
Sertraline
n=11 Participants
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 Participants
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
Prevalence of Depression by Patient Health Questionnaire (PHQ-9) Over Time
Week 4
|
5 score on a scale
Interval 2.0 to 7.0
|
5 score on a scale
Interval 3.0 to 7.0
|
|
Prevalence of Depression by Patient Health Questionnaire (PHQ-9) Over Time
Week 8
|
6 score on a scale
Interval 1.0 to 9.0
|
3 score on a scale
Interval 2.0 to 7.0
|
|
Prevalence of Depression by Patient Health Questionnaire (PHQ-9) Over Time
Week 12
|
2 score on a scale
Interval 0.0 to 9.0
|
2 score on a scale
Interval 0.0 to 3.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeksParticipants' percent adherence to study drug regiment by pharmacy medication counts, representing the percent of the total prescribed medication taken by participants.
Outcome measures
| Measure |
Sertraline
n=11 Participants
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 Participants
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
Adherence to Study Drug
Week 2
|
100 Percent of total prescribed medication t
Interval 100.0 to 100.0
|
100 Percent of total prescribed medication t
Interval 96.0 to 100.0
|
|
Adherence to Study Drug
Week 4
|
100 Percent of total prescribed medication t
Interval 94.0 to 100.0
|
100 Percent of total prescribed medication t
Interval 97.0 to 100.0
|
|
Adherence to Study Drug
Week 8
|
97 Percent of total prescribed medication t
Interval 88.0 to 100.0
|
100 Percent of total prescribed medication t
Interval 96.0 to 100.0
|
|
Adherence to Study Drug
Week 12
|
89 Percent of total prescribed medication t
Interval 63.0 to 100.0
|
100 Percent of total prescribed medication t
Interval 100.0 to 100.0
|
Adverse Events
Sertraline
Serious events: 4 serious events
Other events: 4 other events
Deaths: 0 deaths
Control
Serious events: 3 serious events
Other events: 1 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Sertraline
n=11 participants at risk
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 participants at risk
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
Gastrointestinal disorders
Acute Gastrointestinal bleeding
|
9.1%
1/11 • Number of events 1 • Through week 24
|
0.00%
0/11 • Through week 24
|
|
Psychiatric disorders
Mania with Psychotic Disorder
|
18.2%
2/11 • Number of events 3 • Through week 24
|
0.00%
0/11 • Through week 24
|
|
Vascular disorders
Pulmonary Embolism
|
0.00%
0/11 • Through week 24
|
9.1%
1/11 • Number of events 1 • Through week 24
|
|
Nervous system disorders
Meningitis
|
0.00%
0/11 • Through week 24
|
9.1%
1/11 • Number of events 1 • Through week 24
|
|
Nervous system disorders
Psychosis with Serotonin Syndrome
|
9.1%
1/11 • Number of events 1 • Through week 24
|
0.00%
0/11 • Through week 24
|
|
Infections and infestations
Death
|
0.00%
0/11 • Through week 24
|
9.1%
1/11 • Number of events 1 • Through week 24
|
Other adverse events
| Measure |
Sertraline
n=11 participants at risk
Fluconazole Standard of Care + Sertraline
Sertraline: sertraline 400mg/day
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
Control
n=11 participants at risk
Fluconazole Standard of Care + Placebo Oral Tablet
Placebo Oral Tablet: matched placebo tablet
Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
27.3%
3/11 • Number of events 5 • Through week 24
|
0.00%
0/11 • Through week 24
|
|
Immune system disorders
Leukopenia
|
0.00%
0/11 • Through week 24
|
9.1%
1/11 • Number of events 1 • Through week 24
|
|
Metabolism and nutrition disorders
Hyponatremia
|
9.1%
1/11 • Number of events 1 • Through week 24
|
0.00%
0/11 • Through week 24
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place