Trial Outcomes & Findings for CAP: Doxazosin in the Treatment of Co-Occurring PTSD and Alcohol Use Disorders (NCT NCT02500602)

Last Updated: 2021-05-13

Results Overview

The primary PTSD outcome measure was the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5; Weathers et al., 2013). The CAPS-5 is a semi-structured interview that measures the DSM-5 symptoms of PTSD and requires the presence of at least one intrusion symptom, one avoidance symptom, two cognition and mood symptoms, and two arousal symptoms for a period of 1 month or more to reach diagnostic threshold. There are 20 symptom items and responses that are rated on a 5-point scale ranging from 0 (absent) to 4 (extreme/incapacitating), with a total PTSD symptom severity score of the sum of the 20 symptom items ranging from 0-80, and lower scores indicating better outcomes (or less severe PTSD symptomology). The CAPS-5 was assessed at end of treatment (week 12).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

144 participants

Primary outcome timeframe

12 Weeks

Results posted on

2021-05-13

Participant Flow

Participant milestones

Participant milestones
Measure	Doxazosin Participants randomly assigned to receive doxazosin (target dose of 16 mg/day). doxazosin: active medication	Placebo Participants randomly assigned to receive Placebo pill placebo: placebo pill
Treatment Phase STARTED	74	70
Treatment Phase COMPLETED	68	69
Treatment Phase NOT COMPLETED	6	1
Follow Up Phase STARTED	68	69
Follow Up Phase COMPLETED	53	47
Follow Up Phase NOT COMPLETED	15	22

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

CAP: Doxazosin in the Treatment of Co-Occurring PTSD and Alcohol Use Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Doxazosin n=74 Participants Participants randomly assigned to receive doxazosin (target dose of 16 mg/day). doxazosin: active medication	Placebo n=70 Participants Participants randomly assigned to receive Placebo pill placebo: placebo pill	Total n=144 Participants Total of all reporting groups
Age, Continuous	46.2 years STANDARD_DEVIATION 10.9 • n=5 Participants	45.5 years STANDARD_DEVIATION 11.4 • n=7 Participants	45.9 years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	62 Participants n=7 Participants	122 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	34 Participants n=5 Participants	36 Participants n=7 Participants	70 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants	29 Participants n=7 Participants	62 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment United States	74 Participants n=5 Participants	70 Participants n=7 Participants	144 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	Doxazosin n=74 Participants Doxazosin (target dose of 16 mg/day). Doxazosin will be initiated at 1 mg/day for the first week, 2mg/day for the second week, 4mg/day for the third week, 8mg/day for the fourth week, and then increase to 16 mg/day for the remaining eight weeks (as tolerated). R doxazosin: active medication	Placebo n=70 Participants Placebo pill placebo: placebo pill
Clinician Administered PTSD Scale	34.2 score on a scale Standard Deviation 9.6	32.5 score on a scale Standard Deviation 8.7

PRIMARY outcome

Timeframe: 12 Weeks

The secondary PTSD outcome measure was the PTSD Checklist-5 (PCL-5; Weathers et al., 2013b). The PCL-5 is 20-item self-report measure that assesses the DSM-5 symptoms of PTSD using a severity rating Likert scale ranging from 0 to 4 that indicates the degree of distress across symptoms (0 = not at all to 4 = extremely). The overall score range is 0-80 (and combines the score for all 20 symptoms), with lower scores representing better outcomes (less severe PTSD symptomology). The PCL-5 was assessed at end of treatment (week 12).

Outcome measures

Outcome measures
Measure	Doxazosin n=74 Participants Doxazosin (target dose of 16 mg/day). Doxazosin will be initiated at 1 mg/day for the first week, 2mg/day for the second week, 4mg/day for the third week, 8mg/day for the fourth week, and then increase to 16 mg/day for the remaining eight weeks (as tolerated). R doxazosin: active medication	Placebo n=70 Participants Placebo pill placebo: placebo pill
PTSD Checklist (PCL-5)	47.3 score on a scale Standard Deviation 14.5	46.9 score on a scale Standard Deviation 15.2

PRIMARY outcome

Timeframe: 12 Weeks

The TLFB obtains retrospective self-report of substance use by using a calendar and memory prompts to stimulate recall (Sobell \& Sobell, 1992). Quantity and frequency assessments are made using this instrument (e.g., total number of standard drink units, percent of days using) as well as abstinence (yes/no). TLFB yields consistently high test-retest correlations and correlates well with other self-reports and collateral reports (Sobell et al., 2003). The TLFB assesses frequency and amount of substance use over a pre-determined timeframe. TLFB data were collected throughout the trial, and the values reported here represent the TLFB data at end of treatment (week 12).

Outcome measures

Outcome measures
Measure	Doxazosin n=74 Participants Doxazosin (target dose of 16 mg/day). Doxazosin will be initiated at 1 mg/day for the first week, 2mg/day for the second week, 4mg/day for the third week, 8mg/day for the fourth week, and then increase to 16 mg/day for the remaining eight weeks (as tolerated). R doxazosin: active medication	Placebo n=70 Participants Placebo pill placebo: placebo pill
Time Line Follow Back (TLFB) percentage of days drinking	53.7 percent Standard Deviation 34.8	48.1 percent Standard Deviation 41.2
Time Line Follow Back (TLFB) percent heavy days drinking	37 percent Standard Deviation 37.6	38.6 percent Standard Deviation 38

Adverse Events

Doxazosin

Serious events: 12 serious events

Other events: 48 other events

Deaths: 0 deaths

Placebo

Serious events: 9 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Doxazosin n=74 participants at risk Participants randomly assigned to receive doxazosin (target dose of 16 mg/day). doxazosin: active medication	Placebo n=70 participants at risk Participants randomly assigned to receive Placebo pill placebo: placebo pill
Cardiac disorders Chest Pain	0.00% 0/74 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	1.4% 1/70 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Gastrointestinal disorders Hemorrhoids	1.4% 1/74 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	0.00% 0/70 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Gastrointestinal disorders Pancreatitis	1.4% 1/74 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	0.00% 0/70 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
General disorders Dehydration	1.4% 1/74 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	0.00% 0/70 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Musculoskeletal and connective tissue disorders Hernia	1.4% 1/74 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	0.00% 0/70 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Musculoskeletal and connective tissue disorders Fracture	0.00% 0/74 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	1.4% 1/70 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Psychiatric disorders Depression	1.4% 1/74 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	0.00% 0/70 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Psychiatric disorders Suicidal Ideation/Attempt	4.1% 3/74 • Number of events 3 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	1.4% 1/70 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Psychiatric disorders Anger/Frustration	1.4% 1/74 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	0.00% 0/70 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Psychiatric disorders Homicidal Ideation/Aggression	1.4% 1/74 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	1.4% 1/70 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Psychiatric disorders Substance Use	1.4% 1/74 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	4.3% 3/70 • Number of events 3 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Psychiatric disorders Panic Attack/Anxiety	0.00% 0/74 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	1.4% 1/70 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Endocrine disorders Diabetes Complications	1.4% 1/74 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	1.4% 1/70 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.

Other adverse events

Additional Information

Sudie Back

Medical University of South Carolina

Phone: 843-792-9383

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Doxazosin n=74 participants at risk Participants randomly assigned to receive doxazosin (target dose of 16 mg/day). doxazosin: active medication	Placebo n=70 participants at risk Participants randomly assigned to receive Placebo pill placebo: placebo pill
Psychiatric disorders Depression	9.5% 7/74 • Number of events 7 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	7.1% 5/70 • Number of events 5 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Cardiac disorders Hypotension	0.00% 0/74 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	5.7% 4/70 • Number of events 4 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Cardiac disorders Hypertension	5.4% 4/74 • Number of events 4 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	0.00% 0/70 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Gastrointestinal disorders Diarrhea	6.8% 5/74 • Number of events 5 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	4.3% 3/70 • Number of events 3 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Gastrointestinal disorders Stomach Virus/Cramping/Nausea	17.6% 13/74 • Number of events 13 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	8.6% 6/70 • Number of events 6 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
General disorders Cold/Sinus/Congestion	9.5% 7/74 • Number of events 7 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	20.0% 14/70 • Number of events 14 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
General disorders Fatigue	2.7% 2/74 • Number of events 2 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	7.1% 5/70 • Number of events 5 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
General disorders Generalized Pain	6.8% 5/74 • Number of events 5 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	4.3% 3/70 • Number of events 3 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
General disorders Accident/Injury	10.8% 8/74 • Number of events 8 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	5.7% 4/70 • Number of events 4 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Metabolism and nutrition disorders Joint/Muscle Pain	14.9% 11/74 • Number of events 11 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	22.9% 16/70 • Number of events 16 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Nervous system disorders Drowsiness/Grogginess	14.9% 11/74 • Number of events 11 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	8.6% 6/70 • Number of events 6 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Nervous system disorders Dizziness/Lightheadedness	12.2% 9/74 • Number of events 9 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	27.1% 19/70 • Number of events 19 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Psychiatric disorders Sleep Problems	13.5% 10/74 • Number of events 10 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	14.3% 10/70 • Number of events 10 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Psychiatric disorders Vivid Dreams/Nightmares	10.8% 8/74 • Number of events 8 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	17.1% 12/70 • Number of events 12 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.
Psychiatric disorders Emotional Distress	1.4% 1/74 • Number of events 1 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.	7.1% 5/70 • Number of events 5 • AEs collected from baseline (if baseline lasted longer than one appointment) through follow up (12 week treatment phase and 6 week follow up - approximately 20 weeks) Participants were asked about any changes in health or existing symptoms at each visit.