Trial Outcomes & Findings for Caffeine and Neurologic Recovery Following Surgery and General Anesthesia (NCT NCT03577730)

Results Overview

Postoperative opioid consumption, oral morphine equivalents (mg)

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

71 participants

Primary outcome timeframe

through postoperative day 3

Results posted on

2021-10-06

Participant Flow

A total of 71 subjects were consented. Data is reported for a total of 60 subjects.

Participant milestones

Participant milestones
Measure	Experimental Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Overall Study STARTED	34	31
Overall Study Received Treatment	33	31
Overall Study COMPLETED	30	30
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Overall Study Physician Decision	3	1
Overall Study Did not receive allocated intervention	1	0

Baseline Characteristics

Caffeine and Neurologic Recovery Following Surgery and General Anesthesia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental n=30 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=30 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.	Total n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=93 Participants	23 Participants n=4 Participants	44 Participants n=27 Participants
Age, Categorical >=65 years	9 Participants n=93 Participants	7 Participants n=4 Participants	16 Participants n=27 Participants
Sex: Female, Male Female	17 Participants n=93 Participants	15 Participants n=4 Participants	32 Participants n=27 Participants
Sex: Female, Male Male	13 Participants n=93 Participants	15 Participants n=4 Participants	28 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=93 Participants	29 Participants n=4 Participants	57 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	29 Participants n=93 Participants	30 Participants n=4 Participants	59 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	30 participants n=93 Participants	30 participants n=4 Participants	60 participants n=27 Participants

PRIMARY outcome

Timeframe: through postoperative day 3

Postoperative opioid consumption, oral morphine equivalents (mg)

Outcome measures

Outcome measures
Measure	Experimental n=30 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=30 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Cumulative Opioid Consumption: Postoperative Opioid Consumption, Oral Morphine Equivalents (mg)	77 oral morphine equivalents (mg) Interval 33.0 to 182.0	51 oral morphine equivalents (mg) Interval 15.0 to 117.0

SECONDARY outcome

Timeframe: Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol.

Visual Analogue Scale (mm, 0-100, 0 = no pain, 100 = worst pain imaginable)

Outcome measures

Outcome measures
Measure	Experimental n=30 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=30 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Acute Pain (Patient-reported) as Assessed by Visual Analogue Scale	40 score on a scale Interval 19.0 to 65.0	39 score on a scale Interval 18.0 to 60.0

SECONDARY outcome

Timeframe: Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol.

Behavioral Pain Scale, on a scale ranging from 3 to 12 when 3 is no pain and 12 is maximum pain

Outcome measures

Outcome measures
Measure	Experimental n=30 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=30 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Acute Pain (Observer-reported) as Assessed by Behavioral Pain Scale	3 score on a scale Interval 3.0 to 3.0	3 score on a scale Interval 3.0 to 3.0

SECONDARY outcome

Timeframe: Duration of time from surgical dressing completion to anesthetic emergence (min); generally expected to be between 10 and 60 minutes

Population: Data at baseline or post-operative point was not available for some participants, so data is reported only for those who had complete baseline and post-operative data.

Time from surgical dressing on to anesthetic emergence (min)

Outcome measures

Outcome measures
Measure	Experimental n=27 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=24 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Time Until Anesthetic Emergence	8 Minutes Interval 6.0 to 15.0	10 Minutes Interval 6.0 to 17.0

SECONDARY outcome

Timeframe: baseline through postoperative day 3

Number (n) of participants with positive screens (score ≥8) using the Hospitalized Anxiety and Depression Scale (HADS-D) (n, 0-21, 0 = normal, 21 = presence of severe depression symptoms)

Outcome measures

Outcome measures
Measure	Experimental n=28 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=27 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Number of Participants With Depression as Assessed by the Hospitalized Anxiety and Depression Scale (HADS-D)	2 Participants	1 Participants

SECONDARY outcome

Timeframe: baseline through postoperative day 3

Population: Data at baseline or post-operative point was not available for some participants, so data is reported only for those who had complete baseline and post-operative data.

Number (n) of participants with positive screens (score ≥8) using the Hospitalized Anxiety and Depression Scale (HADS-A) (n, 0-21, 0 = normal, 21 = presence of severe anxiety symptoms)

Outcome measures

Outcome measures
Measure	Experimental n=28 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=27 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Number of Participants With Anxiety as Assessed by the Hospitalized Anxiety and Depression Scale (HADS-A)	2 Participants	2 Participants

SECONDARY outcome

Timeframe: morning of surgery baseline compared to postanesthesia care unit. Postanesthesia care unit measurement approximately 60 minutes after end of surgery

Population: Data at baseline or post-operative point was not available for some participants, so data is reported only for those who had complete baseline and post-operative data.

Trail Making Test scores (seconds, 10-300,10 = fastest reported completion, 300 = maximum time allowed for completion). The change was calculated from the value at post anesthesia minus value at baseline. Higher values are considered to be worse outcomes.

Outcome measures

Outcome measures
Measure	Experimental n=17 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=11 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Cognitive Function as Assessed by Trail Making Test	10 score on a scale Interval 2.0 to 25.0	16 score on a scale Interval 6.0 to 39.0

SECONDARY outcome

Timeframe: postoperative day 3

Population: Data at baseline or post-operative point was not available for some participants, so data is reported only for those who had complete baseline and post-operative data.

Positive Affect Score (n, 10-50, 10 = least positive affect, 50 = most positive affect) via PANAS (Positive and Negative Affect Schedule)

Outcome measures

Outcome measures
Measure	Experimental n=27 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=26 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Positive Affect as Assessed by PANAS (Positive and Negative Affect Schedule)	35 score on a scale Interval 28.0 to 39.0	35 score on a scale Interval 27.0 to 37.0

SECONDARY outcome

Timeframe: postoperative day 3

Population: Data at baseline or post-operative point was not available for some participants, so data is reported only for those who had complete baseline and post-operative data.

Negative Affect Score (n, 10-50, 10 = least negative affect, 50 = most negative affect) via PANAS (Positive and Negative Affect Schedule)

Outcome measures

Outcome measures
Measure	Experimental n=27 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=26 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Negative Affect as Assessed by PANAS (Positive and Negative Affect Schedule)	12 score on a scale Interval 10.0 to 16.0	12 score on a scale Interval 10.0 to 17.0

SECONDARY outcome

Timeframe: By afternoon of postoperative day (POD) 3

Number (n) of participants who has experienced at least one episode of delirium by the postoperative day 3 time point, as determined by daily Confusion Assessment Method (CAM).

Outcome measures

Outcome measures
Measure	Experimental n=30 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=30 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Percentage of Delirious Patients Per Group	7 Participants	14 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Preoperative (once before surgery on day of surgery)

Population: Richards Campbell Sleep Questionnaire (RCSQ)

Self-report instrument for measuring sleep quality. Visual Analogue Scale (mm, 0-100, 0 =Deep sleep , 100 =Light sleep)

Outcome measures

Outcome measures
Measure	Experimental n=30 Participants Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=30 Participants Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Richards Campbell Sleep Questionnaire (RCSQ)	58 score on a scale Standard Deviation 26	56 score on a scale Standard Deviation 28

Adverse Events

Experimental

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Control

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Experimental n=33 participants at risk Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=31 participants at risk Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Renal and urinary disorders Acute kidney injury	0.00% 0/33 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).	3.2% 1/31 • Number of events 1 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).
Gastrointestinal disorders Ileus requiring re-admittance to hospital	0.00% 0/33 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).	3.2% 1/31 • Number of events 1 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).
Gastrointestinal disorders Small bowel obstruction	0.00% 0/33 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).	3.2% 1/31 • Number of events 1 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).
Infections and infestations Urosepsis	0.00% 0/33 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).	3.2% 1/31 • Number of events 1 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).
Infections and infestations Pelvic absess	3.0% 1/33 • Number of events 1 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).	0.00% 0/31 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).
General disorders Hypoxia	3.0% 1/33 • Number of events 1 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).	0.00% 0/31 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).

Other adverse events

Other adverse events
Measure	Experimental n=33 participants at risk Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Caffeine Citrate: Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.	Control n=31 participants at risk Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group. Dextrose Water: Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.
Gastrointestinal disorders Ileus	15.2% 5/33 • Number of events 5 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).	0.00% 0/31 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).
General disorders Nausea	9.1% 3/33 • Number of events 3 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).	0.00% 0/31 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).
General disorders Nausea with emesis	0.00% 0/33 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).	12.9% 4/31 • Number of events 4 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).
General disorders Dehydration	0.00% 0/33 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).	6.5% 2/31 • Number of events 2 • Data were collected at 30 days. AEs are presented for all 64 participants who received the study drug (caffeine or placebo).

Additional Information

Phillip Vlisides

University of Michigan

Phone: 734-936-4280

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place