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NCT00532493: PACT

Cooperative Studies Program #563 - Prazosin and Combat Trauma PTSD

Completed Phase 3 Results posted Last updated 1 May 2018
What this trial tests

Phase 3 trial testing prazosin in PTSD in 304 participants. Completed in 31 May 2013.

Timeline
6 January 2010
Primary endpoint
28 February 2013
31 May 2013

Quick facts

Lead sponsorVA Office of Research and Development
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment304
Start date6 January 2010
Primary completion28 February 2013
Estimated completion31 May 2013
Sites15 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

VA Office of Research and Development — full company profile →

Who can join

18 and older, any sex, with PTSD or Sleep Disorders. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

CAPS Recurrent Distressing Dreams Item Primary · This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported.

Change from baseline in frequency and/or severity of combat trauma-related nightmares will be assessed by the CAPS Recurrent Distressing Dreams item. Possible range for Recurrent Distressing Dreams is 0-8. Higher score indicates more severe PTSD symptoms.

GroupValue95% CI
Prazosin Group-1.9± 2.1
Placebo Group-1.7± 2.3
Pittsburgh Sleep Quality Index (PSQI) Primary · This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported.

Change from baseline in possible range for PSQI global score 0-21. Higher PSQI score indicates worse quality of sleep.

GroupValue95% CI
Prazosin-2.3± 4.2
Placebo-2.1± 4
Pittsburgh Sleep Quality Index Secondary · This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

Change from baseline in possible range for PSQI global score 0-21. Higher PSQI score indicates worse quality of sleep.

Baseline
GroupValue95% CI
Prazosin14.4± 3.3
Placebo14.7± 3.5
Change at Week 6
GroupValue95% CI
Prazosin-2.1± 3.9
Placebo-2.4± 4.2
Change at Week 10
GroupValue95% CI
Prazosin-2.3± 4.2
Placebo-2.1± 4
Change at Week 14
GroupValue95% CI
Prazosin-3.1± 3.9
Placebo-2.7± 3.9
Change at Week 18
GroupValue95% CI
Prazosin-2.4± 4.1
Placebo-2.8± 4
Change at Week 22
GroupValue95% CI
Prazosin-2.9± 4
Placebo-2.7± 4.2
Change at Week 26
GroupValue95% CI
Prazosin-2.9± 4.3
Placebo-2.7± 4.1
CAPS Recurrent Distressing Dreams Item Secondary · This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination) to assess temporal course of changes in symptoms in response to prazosin or placebo.

Change from baseline in frequency and/or severity of combat trauma-related nightmares will be assessed by the CAPS Recurrent Distressing Dreams item. Possible range for Recurrent Distressing Dreams is 0-8. Higher score indicates more severe PTSD symptoms.

Baseline
GroupValue95% CI
Prazosin Group6.3± 0.9
Placebo Group6.3± 0.9
Change at Week 6
GroupValue95% CI
Prazosin Group-1.3± 1.8
Placebo Group-1.4± 1.8
Change at Week 10
GroupValue95% CI
Prazosin Group-1.9± 2.1
Placebo Group-1.7± 2.3
Change at Week 14
GroupValue95% CI
Prazosin Group-2.2± 2.2
Placebo Group-2.5± 2.5
Change at Week 18
GroupValue95% CI
Prazosin Group-1.8± 2.3
Placebo Group-2.4± 2.5
Change at Week 22
GroupValue95% CI
Prazosin Group-2.4± 2.3
Placebo Group-2.5± 2.4
Change at Week 26
GroupValue95% CI
Prazosin Group-2.3± 2.5
Placebo Group-2.2± 2.5
Clinical Global Impression of Change Secondary · This secondary outcome measure was administered at 6, 10, 14, 18, 22 and 26 weeks (or early termination).

Change from baseline in possible range for Clinical Global Impression of Change (CGIC) 1-7. As compared to baseline global condition, 1 is marked improvement, 2 is moderate improvement, 3 is minimal improvement, 4 is no change, 5 is minimal worsening, 6 is moderate worsening, and 7 is marked worsening.

Week 6
GroupValue95% CI
Prazosin3.2± 1.2
Placebo3.3± 1.3
Week 10
GroupValue95% CI
Prazosin3.3± 1.4
Placebo3.3± 1.4
Week 14
GroupValue95% CI
Prazosin3± 1.4
Placebo3± 1.4
Week 18
GroupValue95% CI
Prazosin3.2± 1.3
Placebo3± 1.4
Week 22
GroupValue95% CI
Prazosin2.9± 1.4
Placebo2.9± 1.3
Week 26
GroupValue95% CI
Prazosin2.9± 1.6
Placebo2.9± 1.4
Total CAPS Score Secondary · The total CAPS was administered at baseline, 6, 10, 18, and 26 weeks (or early termination).

Change from baseline in possible range for CAPS total score is 0-136. Higher score indicates more severe PTSD symptoms.

Baseline
GroupValue95% CI
Prazosin80.7± 15.5
Placebo81.9± 17.1
Change at Week 6
GroupValue95% CI
Prazosin-9.9± 16
Placebo-9.1± 16.9
Change at Week 10
GroupValue95% CI
Prazosin-11.4± 17.2
Placebo-12.1± 19.4
Change at Week 18
GroupValue95% CI
Prazosin-11.6± 18.3
Placebo-17.2± 21.7
Change at Week 26
GroupValue95% CI
Prazosin-14.1± 21.8
Placebo-16.2± 24.2
Clinical Global Impression of Change (CGIC) Primary · This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported.

Change from baseline in possible range for Clinical Global Impression of Change 1-7. As compared to baseline global condition, 1 is marked improvement, 2 is moderate improvement, 3 is minimal improvement, 4 is no change, 5 is minimal worsening, 6 is moderate worsening, and 7 is marked worsening.

GroupValue95% CI
Prazosin3.3± 1.4
Placebo3.3± 1.4
PTSD Checklist-Military Version (PCL-M) Score Secondary · This secondary outcome was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks to assess change in PTSD symptom severity.

Change from baseline in possible range for PCL-M score 17-85. Higher PCL score indicates greater propensity for chronic and delayed PTSD.

Baseline
GroupValue95% CI
Prazosin62.5± 11.1
Placebo64.3± 12.2
Change at Week 6
GroupValue95% CI
Prazosin-6.3± 10.6
Placebo-6.2± 11
Change at Week 10
GroupValue95% CI
Prazosin-7± 12.7
Placebo-5.8± 11.6
Change at Week 14
GroupValue95% CI
Prazosin-8.1± 12.5
Placebo-7.6± 11.6
Change at Week 18
GroupValue95% CI
Prazosin-7.2± 12.3
Placebo-8.4± 13.3
Change at Week 22
GroupValue95% CI
Prazosin-7.1± 12.9
Placebo-9.2± 13.5
Change at Week 26
GroupValue95% CI
Prazosin-8.2± 13.8
Placebo-9.7± 14
Patient Health Questionnaire-9 (PHQ9) Secondary · This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

Change from baseline in possible range for PHQ9 score is 0-27. Higher PHQ9 score indicates more severe depression.

Baseline
GroupValue95% CI
Prazosin13.7± 5.9
Placebo14.6± 5.9
Change at Week 6
GroupValue95% CI
Prazosin-1.6± 4.7
Placebo-2.8± 5.1
Change at Week 10
GroupValue95% CI
Prazosin-1.9± 5.1
Placebo-2.2± 5.1
Change at Week 14
GroupValue95% CI
Prazosin-1.9± 5.2
Placebo-2.6± 5.3
Change at Week 18
GroupValue95% CI
Prazosin-1.6± 5.3
Placebo-2.4± 5.5
Change at Week 22
GroupValue95% CI
Prazosin-2.2± 5.6
Placebo-2.5± 5.9
Change at Week 26
GroupValue95% CI
Prazosin-2± 5.5
Placebo-2.8± 5.8
SF-12 Physical Standardized Score (SF-12 PCS) Secondary · This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

Change from baseline in possible range for SF-12 PCS is 6-72. Higher SF-12 score indicates better level of health.

Baseline
GroupValue95% CI
Prazosin35.4± 14.5
Placebo34.2± 12.2
Change at Week 6
GroupValue95% CI
Prazosin1.8± 9.7
Placebo0.8± 10.2
Change at Week 10
GroupValue95% CI
Prazosin0.3± 10
Placebo0.3± 10.4
Change at Week 14
GroupValue95% CI
Prazosin1.4± 10.1
Placebo0.3± 10.9
Change at Week 18
GroupValue95% CI
Prazosin0.5± 10
Placebo-0.4± 11.4
Change at Week 22
GroupValue95% CI
Prazosin1.1± 10.9
Placebo-0.8± 13.2
Change at Week 26
GroupValue95% CI
Prazosin0.7± 11.8
Placebo-0.2± 11.9
SF-12 Mental Standardized Score (SF-12 MCS) Secondary · This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

Change from baseline in possible range for SF-12 MCS is 5-76. Higher SF-12 score indicates better level of health.

Baseline
GroupValue95% CI
Prazosin38.2± 9.1
Placebo39.4± 8.4
Change at Week 6
GroupValue95% CI
Prazosin-2± 9.2
Placebo-1.3± 8.5
Change at Week 10
GroupValue95% CI
Prazosin-1± 9.2
Placebo-1.1± 8.7
Change at Week 14
GroupValue95% CI
Prazosin-1.5± 7.9
Placebo-1± 9.7
Change at Week 18
GroupValue95% CI
Prazosin-0.2± 8.4
Placebo-0.7± 8.8
Change at Week 22
GroupValue95% CI
Prazosin-0.8± 8.9
Placebo-0.6± 9.4
Change at Week 26
GroupValue95% CI
Prazosin-0.7± 8.7
Placebo-0.8± 9.5
Quality of Life Inventory (QOLI) Secondary · This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

Change from baseline in possible range for QOLI is -6 to 6. Higher QOLI indicates better satisfaction with life.

Baseline
GroupValue95% CI
Prazosin0.1± 1.9
Placebo0± 1.9
Change at Week 6
GroupValue95% CI
Prazosin0.1± 1.5
Placebo0± 1.4
Change at Week 10
GroupValue95% CI
Prazosin0± 1.3
Placebo0.1± 1.7
Change at Week 14
GroupValue95% CI
Prazosin0.1± 1.5
Placebo0± 1.5
Change at Week 18
GroupValue95% CI
Prazosin0.3± 1.3
Placebo0.1± 1.6
Change at Week 22
GroupValue95% CI
Prazosin0.1± 1.4
Placebo0.1± 1.9
Change at Week 26
GroupValue95% CI
Prazosin0.2± 1.4
Placebo0.2± 2

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Prazosin Group
Serious: 18/152 (12%)
Deaths:
Placebo Group
Serious: 17/152 (11%)
Deaths:

Serious adverse events (30 terms)

ReactionSystemPrazosin GroupPlacebo Group
Suicidal ideationPsychiatric disorders
AnaemiaBlood and lymphatic system disorders
Coronary artery diseaseCardiac disorders
Myocardial infarctionCardiac disorders
Arteriovenous malformationCardiac disorders
Retinal detachmentEye disorders
Abdominal herniaGastrointestinal disorders
Haemorrhagic erosive gastritisGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Chest painGeneral disorders
Drug withdrawal syndromeGeneral disorders
Campylobacter infectionInfections and infestations
CellulitisInfections and infestations
PneumoniaInfections and infestations
Ankle fractureInjury, poisoning and procedural complications
Arthropod stingInjury, poisoning and procedural complications
Delayed recovery from anaesthesiaInjury, poisoning and procedural complications
Endotracheal intubation complicationInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Road traffic accidentInjury, poisoning and procedural complications
Toxicity to various agentsInjury, poisoning and procedural complications
Fracture malunionMusculoskeletal and connective tissue disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Basal ganglia infarctionNervous system disorders
Sudden onset of sleepNervous system disorders
Other adverse events (245 terms — click to expand)

ReactionSystemPrazosin GroupPlacebo Group
DizzinessNervous system disorders
HeadacheNervous system disorders
AstheniaGeneral disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Dizziness posturalNervous system disorders
SomnolenceNervous system disorders
NauseaGastrointestinal disorders
Depressed moodPsychiatric disorders
InsomniaPsychiatric disorders
PollakiuriaRenal and urinary disorders
PalpitationsCardiac disorders
Suicidal ideationPsychiatric disorders
OedemaGeneral disorders
DepressionPsychiatric disorders
IncontinenceRenal and urinary disorders
Dry mouthGastrointestinal disorders
Orthostatic hypotensionVascular disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
DyspepsiaGastrointestinal disorders
Chest painGeneral disorders
Oedema peripheralGeneral disorders
NasopharyngitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Abdominal discomfortGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
TinnitusEar and labyrinth disorders
Abdominal pain upperGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
PainGeneral disorders
PyrexiaGeneral disorders

Most-reported serious reactions: Suicidal ideation, Anaemia, Coronary artery disease, Myocardial infarction, Arteriovenous malformation, Retinal detachment, Abdominal hernia, Haemorrhagic erosive gastritis.

Data from ClinicalTrials.gov NCT00532493 adverse events section.

Sponsor's own description

Background: Posttraumatic stress disorder (PTSD) is a debilitating and disabling mental disorder that afflicts at least 25% of Veterans who have suffered life-threatening war zone trauma. Trauma-related nightmares and sleep disturbance are among the most treatment-resistant PTSD symptoms in Veterans. Increased responsiveness to central nervous system (CNS) norepinephrine (NE) contributes to the pathophysiology of overall PTSD and treatment-resistant nighttime symptoms. Placebo-controlled pilot studies demonstrate that the generically available CNS-active alpha-1 adrenoreceptor antagonist prazosin substantially reduces PTSD trauma nightmares and sleep disturbance and improves global clinical status (sense of well being and ability to function) in Veterans. Objective: The primary objective is to demonstrate in a large multi-site placebo-controlled trial in Veterans with war zone trauma-induced PTSD that prazosin is efficacious for PTSD trauma nightmares, sleep disturbance, and global clinical status. A secondary objective is to demonstrate prazosin effectiveness for these outcome measures during clinically meaningful long-term (26 week) maintenance treatment of PTSD. The investigators will also address prazosin efficacy and long-term effectiveness for improving total PTSD symptoms, comorbid depression, quality of life, and physical functioning. Methods: This 26 week randomized double-blind placebo-controlled study is designed to demonstrate both short term efficacy and long term effectiveness of prazosin for PTSD. The research design encompasses a shorter-term, more tightly controlled efficacy component and a longer-term, more .real world. effectiveness component. Three hundred twenty-six Veterans with war zone -related PTSD and persistent trauma nightmares will be randomized 1:1 to prazosin or placebo. Study drug will be increased using a flexible dose titration schedule based on clinical response and adverse effects to an optimum maintenance dose (1-20 mg/day). During the first 10 weeks of the study, participants will be randomized to prazosin or placebo. Previous psychotropic medications and/or psychotherapy will be maintained constant. Short term efficacy will be determined during the first 10 weeks. During the remaining 16 weeks of the 26 week trial, subjects will continue to receive stable-dose double-blind prazosin or placebo, but will have the option to receive additional psychotropic medications and/or psychotherapeutic interventions, as needed, per the judgment of the study Clinician Prescriber. It is hypothesized that prazosin will remain more clinically effective than placebo at the end of the 26-week trial, demonstrating that prazosin adds benefit over-and-above other treatments that are naturalistically administered by providers in a .real world. clinical setting. Prazosin will be judged efficacious at 10 weeks if superior to placebo on all three primary outcome measures assessing trauma nightmares, sleep disturbance, and global clinical status: the Recurrent Distressing Dreams item of the Clinician Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index (PSQI), and the Clinical Global Impression of Change (CGIC). Secondary outcome measures will assess prazosin effects on total PTSD symptoms, depression, physical functioning, and quality of life. Adverse effects and cardiovascular measures, including supine and standing blood pressure (BP) and heart rate (HR) will be assessed.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans.
    Raskind MA, Peskind ER, Chow B, Harris C, et al · · 2018 · cited 190× · PMID 29414272 · DOI 10.1056/nejmoa1507598
  2. Treating nightmares and insomnia in posttraumatic stress disorder: a review of current evidence.
    Nappi CM, Drummond SP, Hall JM. · · 2012 · cited 80× · PMID 21396945 · DOI 10.1016/j.neuropharm.2011.02.029
  3. Anxiety disorders, PTSD and OCD: systematic review of approved psychiatric medications (2008-2024) and pipeline phase III medications.
    Tadros E, Keerthana S, Padder S, Totlani J, et al · · 2025 · cited 3× · PMID 40225810 · DOI 10.7573/dic.2024-11-2
  4. Therapeutic Evaluation and Utilization Analysis of Mental Health Prescription Digital Therapeutics Within the Current Regulatory Landscape.
    Xia SH, Narayanan MM, Swamy V, Franson K. · · 2025 · cited 3× · PMID 39998017 · DOI 10.3390/pharmacy13010019

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