ModOSA: Evaluation of Modafinil vs Placebo for Treatment of Anesthesia Delayed Emergence in Obstructive Sleep Apnea

• Sponsor: Milton S. Hershey Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02494102
• Collaborator: (none)
• Enrollment: 105
• Location: 1
• Arms: 2
• Duration (Months): 26
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether modafinil use in patients with obstructive sleep apnea will improve postoperative delayed emergence after general anesthesia.

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea; Delayed Emergence From Anesthesia	Drug: Modafinil; Drug: Placebo	Phase 4

Detailed Description

This is a randomized, double blind placebo controlled evaluation of modafinil versus placebo for the treatment of general anesthesia related delayed emergence in patients with the diagnosis of obstructive sleep apnea. 124 patients will be recruited and randomized on the day of surgery to receive 200mg modafinil or placebo. After randomization, patients will proceed to the operative suite for surgical procedure under general anesthesia. The primary outcome measured will be post-anesthesia care unit length of stay. Secondary outcomes will include performance on a post-anesthesia recovery scale.

Study Design

• Study Type: Interventional
• Actual Enrollment: 105 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: double blind randomized placebo controlled trialdouble blind randomized placebo controlled trial
• Masking: Double (Participant, Investigator)
• Masking Description: Computer generated randomization list, subject, clinical team and research team blinded to intervention
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Placebo Controlled Evaluation of Modafinil vs Placebo for the Treatment of General Anesthesia Related Delayed Emergence in Patients With the Diagnosis of Obstructive Sleep Apnea
• Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Administered Placebo day of surgery immediately prior to general anesthesia and surgery	Drug: Placebo
Active Comparator: Intervention Administered Modafinil 200mg day of surgery prior to general anesthesia and surgery	Drug: Modafinil; Atypical Psychomotor stimulant; Other Names: Armodafinil Provigil

Outcome Measures

Primary Outcome Measures

1. Length of Time From Extubation to Discharge From Postanesthesia Recovery Unit [24 hours]

   Length of time of above compared between groups

Secondary Outcome Measures

1. Postanesthesia Quality Recovery Scale Score [baseline and 6 hours after surgery]

   Postanesthesia quality recovery scale (PQRS). Component and aggregate scoring on the scale. Measures physiology, nociceptive, emotional activities of daily living cognitive and overall patient perspective. The scale is dimensionless and the aggregate of all individually tested dimensions is scaled from 17-65. A higher value implies improved postanesthesia recovery. Mean difference was assessed in each patient and aggregated thus patients with no difference between pre- and post-operative scores were zeroed (received a zero score if the difference was zero). A negative value was associated with worse outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 18 years or older

2. Meets diagnostic criteria for obstructive sleep apnea

3. Willing and able to comply with study procedures

4. Willing and able to provide informed consent

5. If female, not pregnant or lactating and willing to use an acceptable method of barrier birth control (e.g. condoms) for one month after surgery and discontinuation of study medication (modafinil may reduce the effectiveness of steroidal contraception for one month after discontinuation)

Exclusion Criteria:

1. Have a medical condition that, in the study physician's judgment, may interfere with safe participation (active cardiac conditions such as angina, recent myocardial infarction w/in 6 months, severe renal or liver disease, unstable diabetes, or elevated liver enzymes greater than twice normal).

2. Have a current neurological disorder (e.g. organic brain disease, dementia) or major psychiatric condition that would impair the collection of data (schizophrenia, bipolar illness).

3. Currently on prescription medication that is known to interact with the study drug. (ethinylestradiol and triazolam).

4. Have current dependence on cocaine, methamphetamine, alcohol or benzodiazepines (DSM-IV criteria).

5. Have a history of severe valvular heart disease, severe left ventricular hypertrophy, cardiac arrhythmias, angina, cardiac syncope, or pre-syncope or myocardial infarction <6 months.

6. Have a history of uncontrolled or poorly controlled essential hypertension, or a heart rate greater than 70% of the maximum heart rate expected for their age (Formula: 0.70(220 - age).

7. Any condition, in the opinion of the principal investigators that would compromise patient safety.

8. A documented history of sensitivity to modafinil.

9. Current Modafinil use for daytime somnolence associated with obstructive sleep apnea.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Penn State Hershey Medical Center	Hershey	Pennsylvania	United States	17033

Sponsors and Collaborators

• Milton S. Hershey Medical Center

Investigators

• Principal Investigator: Zyad J Carr, M.D., Milton S. Hershey Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 28, 2017

More Information

Publications

• Arnulf I, Homeyer P, Garma L, Whitelaw WA, Derenne JP. Modafinil in obstructive sleep apnea-hypopnea syndrome: a pilot study in 6 patients. Respiration. 1997;64(2):159-61.
• Galvin E, Boesjes H, Hol J, Ubben JF, Klein J, Verbrugge SJ. Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve patient psychomotor skills. Acta Anaesthesiol Scand. 2010 Feb;54(2):154-61. doi: 10.1111/j.1399-6576.2009.02093.x. Epub 2009 Aug 31.
• Jasinski DR, Kovacević-Ristanović R. Evaluation of the abuse liability of modafinil and other drugs for excessive daytime sleepiness associated with narcolepsy. Clin Neuropharmacol. 2000 May-Jun;23(3):149-56. Review.
• Jasinski DR. An evaluation of the abuse potential of modafinil using methylphenidate as a reference. J Psychopharmacol. 2000 Mar;14(1):53-60.
• Larijani GE, Goldberg ME, Hojat M, Khaleghi B, Dunn JB, Marr AT. Modafinil improves recovery after general anesthesia. Anesth Analg. 2004 Apr;98(4):976-981. doi: 10.1213/01.ANE.0000108485.29288.B4.
• Minzenberg MJ, Carter CS. Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology. 2008 Jun;33(7):1477-502. Epub 2007 Aug 22. Review.
• Moldofsky H, Broughton RJ, Hill JD. A randomized trial of the long-term, continued efficacy and safety of modafinil in narcolepsy. Sleep Med. 2000 Apr 1;1(2):109-116.
• Pack AI, Black JE, Schwartz JR, Matheson JK. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med. 2001 Nov 1;164(9):1675-81.
• Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM. Dopaminergic role in stimulant-induced wakefulness. J Neurosci. 2001 Mar 1;21(5):1787-94.

• Responsible Party: Zyad J. Carr, M.D., Principal Investigator, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT02494102
• Other Study ID Numbers: CAPITALSTUDY00002957
• First Posted: Jul 10, 2015
• Last Update Posted: Jun 20, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Zyad J. Carr, M.D., Principal Investigator, Milton S. Hershey Medical Center: Obstructive Sleep Apnea; General Anesthesia; Modafinil
• Additional relevant MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Delayed Emergence from Anesthesia; Modafinil

Study Results

Participant Flow

Pre-assignment Detail	16 patients violated the study protocol and were excluded from the study. Exclusions included Day of Surgery refusal of study medication, surgical case cancellation, and surgeon refusal to participate.

Arm/Group Title	Placebo	Modafinil
Arm/Group Description	Administered Placebo day of surgery immediately prior to general anesthesia and surgery Placebo	Administered Modafinil 200mg day of surgery prior to general anesthesia and surgery Modafinil: Atypical Psychomotor stimulant
Period Title: Overall Study
STARTED	42	47
COMPLETED	42	47
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Modafinil	Total
Arm/Group Description	Administered Placebo day of surgery immediately prior to general anesthesia and surgery Placebo	Administered Modafinil 200mg day of surgery prior to general anesthesia and surgery Modafinil: Atypical Psychomotor stimulant	Total of all reporting groups
Overall Participants	42	47	89
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.0 (13)	54 (13)	55 (13)
Sex: Female, Male (Count of Participants)
Female	19 45.2%	24 51.1%	43 48.3%
Male	23 54.8%	23 48.9%	46 51.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Surgery Type (Count of Participants)
abdominal surgey	27 64.3%	30 63.8%	57 64%
orthopedic surgery	2 4.8%	5 10.6%	7 7.9%
gynecology	4 9.5%	7 14.9%	11 12.4%
otolaryngology	8 19%	5 10.6%	13 14.6%
opthalmology	1 2.4%	0 0%	1 1.1%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	38.2 (11.1)	44.9 (11.6)	41.9 (11.3)
Hypertension (participants) [Number]
Number [participants]	26 61.9%	33 70.2%	59 66.3%
History of Delayed Emergence (Count of Participants)
Count of Participants [Participants]	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Length of Time From Extubation to Discharge From Postanesthesia Recovery Unit
Description	Length of time of above compared between groups
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

16 participants violated the study protocol

Arm/Group Title	Placebo	Modafinil
Arm/Group Description	Administered Placebo day of surgery immediately prior to general anesthesia and surgery Placebo	Administered Modafinil 200mg day of surgery prior to general anesthesia and surgery Modafinil: Atypical Psychomotor stimulant
Measure Participants	42	47
Mean (Inter-Quartile Range) [minutes]	53.5	61.0

2. Secondary Outcome

Title	Postanesthesia Quality Recovery Scale Score
Description	Postanesthesia quality recovery scale (PQRS). Component and aggregate scoring on the scale. Measures physiology, nociceptive, emotional activities of daily living cognitive and overall patient perspective. The scale is dimensionless and the aggregate of all individually tested dimensions is scaled from 17-65. A higher value implies improved postanesthesia recovery. Mean difference was assessed in each patient and aggregated thus patients with no difference between pre- and post-operative scores were zeroed (received a zero score if the difference was zero). A negative value was associated with worse outcome.
Time Frame	baseline and 6 hours after surgery

Outcome Measure Data

Analysis Population Description

16 patients violated study protocol and were excluded

Arm/Group Title	Placebo	Modafinil
Arm/Group Description	Administered Placebo day of surgery immediately prior to general anesthesia and surgery Placebo	Administered Modafinil 200mg day of surgery prior to general anesthesia and surgery Modafinil: Atypical Psychomotor stimulant
Measure Participants	42	47
Mean (Standard Deviation) [units on a scale]	-5.67 (4.74)	-8.91 (7.98)

Adverse Events

Time Frame	Perioperative time period (within 24 hours)
Arm/Group Title	Placebo		Intervention
Arm/Group Description	Administered Placebo day of surgery immediately prior to general anesthesia and surgery Placebo		Administered Modafinil 200mg day of surgery prior to general anesthesia and surgery Modafinil: Atypical Psychomotor stimulant
All Cause Mortality
	Placebo		Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/47 (0%)
Serious Adverse Events
	Placebo		Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/47 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/47 (0%)

Limitations/Caveats

Trial terminated for statistical futility on scheduled interim analysis

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.