Trial Outcomes & Findings for Ticagrelor in Severe Community Acquired Pneumonia (NCT NCT01998399)

NCT ID: NCT01998399

Last Updated: 2017-12-11

Results Overview

death during 90 day study period

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 25 participants
• Primary outcome timeframe: 90 days
• Results posted on: 2017-12-11

Participant Flow

Participant milestones

Measure	Ticagrelor Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Overall Study STARTED	12	13
Overall Study COMPLETED	4	4
Overall Study NOT COMPLETED	8	9

Reasons for withdrawal

Measure	Ticagrelor Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Overall Study Lost to Follow-up	1	3
Overall Study Death	4	2
Overall Study Study stopped before dosing completed	3	3
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Ticagrelor in Severe Community Acquired Pneumonia

Baseline characteristics by cohort

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.	Total n=25 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	13 participants n=7 Participants	25 participants n=5 Participants

PRIMARY outcome

Timeframe: 90 days

death during 90 day study period

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
All-cause Mortality	4 participants	2 participants

SECONDARY outcome

Timeframe: 15 days

Population: 2 participants from the Ticagrelor arm and 1 from the placebo arm died during the 15 day period

Not requiring pressor support for hypotension

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Shock Free Days	12.58 days Interval 0.0 to 15.0	11.54 days Interval 0.0 to 15.0

SECONDARY outcome

Timeframe: 29 days

Population: 2 participants from each arm died during the 29 day period

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Ventilator Free Days	24.16 days Interval 16.0 to 29.0	22.3 days Interval 14.0 to 25.0

SECONDARY outcome

Timeframe: Throughout hospitalization (About 2 weeks)

Did the patient die during the hospitalization?

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
In-hospital Mortality	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 29 days

Population: 2 participants from each group died during this time period

Number of days the patient is not in the hospital

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Hospital Free Days	14.16 days Interval 3.0 to 22.0	16.53 days Interval 2.0 to 25.0

SECONDARY outcome

Timeframe: 90 days

Did the patient develop a stroke during the 90 day study?

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Stroke	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 90 days

number of participants that suffered stroke, myocardial infarct, mortality

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Stroke, Myocardial Infarct, Mortality	5 Participants	2 Participants

SECONDARY outcome

Timeframe: 90 days

Did the patient have a myocardial infarction during the 90 day study?

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Myocardial Infarction	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 29 days

Population: 2 participants from each arm died during this period

Only in patients on mechanical ventilation and assuming patient achieves 48 consecutive hours of unassisted breathing

Outcome measures

Measure	Ticagrelor n=8 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=11 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Time to Initiation of Unassisted Breathing	136.9 hours Interval 49.5 to 310.5	173.19 hours Interval 46.65 to 404.15

OTHER_PRE_SPECIFIED outcome

Timeframe: 90 days

Population: only participants that required mechanical ventilation

Outcome measures

Measure	Ticagrelor n=8 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=11 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Need for Re-instituting Assisted or Mechanical Ventilation After Achieving 48 Consecutive Hours of Unassisted Breathing or Comfort Care Chosen (Withdrawal of Support)	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Need for Dialysis	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 29 days

Population: 2 participants from each arm died during this period

Includes ICU readmission if during same hospital stay

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
ICU Length of Stay	8.33 days Interval 3.0 to 13.0	8.77 days Interval 2.0 to 22.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 29 days

In days

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Hospital Length of Stay	14.83 days Interval 4.0 to 26.0	12.46 days Interval 4.0 to 27.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 90 days

(Home, other facility, with or without assisted ventilation)

Outcome measures

Measure	Ticagrelor n=12 Participants Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 Participants Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Discharge Disposition Home	5 Participants	9 Participants
Discharge Disposition Extended Care without Ventilator	4 Participants	2 Participants
Discharge Disposition Extended Care with Ventilator	0 Participants	0 Participants
Discharge Disposition In patient rehabilitation	1 Participants	0 Participants
Discharge Disposition Death prior to discharge	2 Participants	2 Participants

Adverse Events

Ticagrelor

Serious events: 5 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ticagrelor n=12 participants at risk Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 participants at risk Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	8.3% 1/12 • Number of events 1 • 90 days	7.7% 1/13 • Number of events 1 • 90 days
Cardiac disorders Type II MI	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Nervous system disorders Subarachnoid hemorrhage	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Respiratory, thoracic and mediastinal disorders Complicated Para-pneumonic Effusion	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Vascular disorders Deep Vein Thrombosis-Right Leg	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Renal and urinary disorders Urinary Tract Infection	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days

Other adverse events

Measure	Ticagrelor n=12 participants at risk Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days Ticagrelor: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Placebo n=13 participants at risk Placebo 180 mg loading dose followed by 90 mg BID for 90 days. Placebo: Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Blood and lymphatic system disorders Thrombocytosis	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Blood and lymphatic system disorders anemia	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Blood and lymphatic system disorders Leukemoid Reaction	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Cardiac disorders Atrial Fibrillation	16.7% 2/12 • Number of events 2 • 90 days	7.7% 1/13 • Number of events 1 • 90 days
Gastrointestinal disorders dysgeusia	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Gastrointestinal disorders diarrhea	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Vascular disorders deep vein thrombosis	0.00% 0/12 • 90 days	7.7% 1/13 • Number of events 2 • 90 days
Vascular disorders Upper Gastrointestinal Bleed	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Vascular disorders vaginal bleeding	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days
Vascular disorders Hematoma on forearm	8.3% 1/12 • Number of events 1 • 90 days	0.00% 0/13 • 90 days

Additional Information

Gordon Bernard, Professor of Medicine, Associate Vice Chancellor for Research

Vanderbilt University

Phone: 615-343-0077

Email: gordon.bernard@Vanderbilt.Edu

Results disclosure agreements

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