Effectiveness of an Opioid Sparing Pain Regimen in Cardiac Surgery (INOVAOPIOID)

• ClinicalTrials.gov Identifier: NCT03679013
• Recruitment Status: Completed
• First Posted: September 20, 2018
• Last Update Posted: August 7, 2019
• Sponsor: Inova Health Care Services
• Information provided by (Responsible Party): Ramesh Singh, Inova Health Care Services

Study Description

Brief Summary:

The Inova Heart and Vascular Institute (IHVI) perform over 300 coronary artery bypass graft (CABG) surgeries per year. While opioid medications are the institutional standard of care for post-operative pain therapy little is known about the variation in pain scores, incidence of post- operative complications, and cost of hospitalization when an alternative multimodal pain regimen consisting of oral Gabapentin and intravenous Acetaminophen (IV APAP) is utilized.

The objective is to determine whether there is a substantial difference in pain scores, incidence of post-operative complications, and costs associated with hospitalization when a non-opioid multimodal pain regimen is utilized A single- center, open label, prospective, randomized, controlled clinical trial comprised of 20 total patients who have undergone isolated CABG at the IHVI will be conducted. Separate cohorts will include patients receiving opioid medications post-operatively (Group 1) and patients receiving the non-opioid regimen of oral Gabapentin and IV APAP (Group 2) to be followed for 72 hours post CABG surgery.

Main outcome measures include pain scores in both study groups, requests for breakthrough pain medication in both groups, gastrointestinal and respiratory complications of ileus and reduction in tidal volumes or forced vital capacity (FVC) at baseline and at 72 hours,increase in serum AST/ALT, and comparison of cost of hospitalization between groups.

The objective of this pilot study is to provide evidence that multimodal pain therapy utilizing IV APAP and PO Gabapentin will provide more effective pain relief than standard of care opioids as evidenced by pain scores <2. And the reduced consumption of opioids will lead to a reduction in ileus, no increase in AST/ALT, post-operative tidal volumes as assessed by incentive spirometry comparable to pre- surgical values, while also showing a positive effect on the cost of hospitalization.

Condition or disease	Intervention/treatment	Phase
Pain, Postoperative	Drug: Oral Gabapentin and Intravenous Acetaminophen (IV APAP); Drug: Opiate based pain regimen.	Phase 2

Detailed Description:

The Cardiovascular Intensive Care Unit (CVICU) of the Inova Heart and Vascular Institute (IHVI) will be the setting of this clinical trial involving two groups of subjects and comparing the opiate based standard of care regimen currently adopted (Group 1) at the IHVI with a treatment group (Group 2). Group 2 will receive a scheduled multimodal pain regimen consisting of PO (pro ora [oral]) Gabapentin paired with intravenous Acetaminophen. Opioids will be available for breakthrough pain in the treatment group for pain scores greater than 4. The outcomes of total opioid consumption and minimum/ maximum pain scores will be assessed at the 24 hours, 48 hours, 72 hours, and PRN (pro re nata [as the situation demands]) timepoints. Assessment will include amount of opioids consumed in both groups as well as number of requests for breakthrough pain medication in Group 2.

Minimum and maximum pain scores in all study groups will be assessed via Numeric Rating Scale (0-10) as per Inova Health System (IHS) policy; 'Pain Management for the Adult Population', at 24 hours, 48 hours, 72 hours, and PRN with opioid requests in all groups and opioid administration follow up within one hour as per IHS inpatient medication administration policy. Follow up medication administration scores will not be recorded as part of study results.

Secondary assessments will include the incidence of ileus both during hospitalization, increase in aspartate aminotransferase (AST)/ alanine aminotransferase (ALT), post-operative tidal volumes as assessed by incentive spirometry as compared to pre- surgical values, time from Cardiovascular Intensive Care Unit (CVICU) arrival to extubation in both groups, and the effects of an opioid based regimen versus an opioid sparing regimen on cost of medication and hospitalization.

The investigators hypothesize that a scheduled opioid- sparing pain regimen consisting of intravenous Acetaminophen IV APAP and PO Gabapentin for 48 hours post- operatively will reduce opioid consumption while maintaining adequate pain relief as evidenced by pain scores less than two (2), and a reduction in opioid consumption, and that reduced opioid consumption will lead to a reduction in the incidence of ileus, an opioid related side effect, no increase in AST/ALT, post-operative tidal volumes as assessed by incentive spirometry comparable to pre- surgical values, and demonstrate a positive effect on the cost of medication and hospitalization.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study Comparing the Effectiveness of an Opioid- Sparing Analgesic Regimen and an Opioid Based Regimen on Post- Operative Pain Control in Cardiac Surgery Patients (INOVA OPIOID
• Actual Study Start Date: April 19, 2019
• Actual Primary Completion Date: July 12, 2019
• Actual Study Completion Date: July 12, 2019

Arms and Interventions

Arm	Intervention/treatment
Opoid based standard of care regimen.; Inova Heart and Vascular Institute (IHVI) opioid based standard of care regimen given for post operative cardiac surgery pain.	Drug: Opiate based pain regimen.; Standard of care opite based pain regimen.; Other Name: Post operative opioids
Experimental: Opioid sparing pain regimen.; Multimodal pain regimen consisting of PO Gabapentin paired with intravenous Acetaminophen given for post operative cardiac surgery pain.	Drug: Oral Gabapentin and Intravenous Acetaminophen (IV APAP); Scheduled multimodal pain regimen consisting of oral Gabapentin paired with intravenous Acetaminophen following cardiopulmonary bypass surgery.; Other Name: PO Gabapentin and IV APAP

Outcome Measures

Primary Outcome Measures :

1. Pain:Total Opioid Consumption in Group 2 as evidenced by requests for breakthrough opioid medication in Group 2 (experimental group). [ Time Frame: Baseline to 72 hours post cardiopulmonary bypass surgery in Group 2. ]
   Requests for breakthrough opioid medication in Group 2 (experimental group) as an indicator of the effectiveness of the experimental regimen.

Secondary Outcome Measures :

1. Efficacy: Incidence of ileus during hospitalization. [ Time Frame: Surgery completion through study completion up to one week. ]
   Occurrence of ileus during hospitalization.
2. Rise in Serum aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) increase.(AST) greater than 168. ALT greater than 105. This will be measured via phlebotomy procedure drawn by the bedside nurse. [ Time Frame: Surgery completion through study completion up to one week. ]
   Serum aspartate aminotransferase (AST) greater than 168. Alanine aminotransferase greater than 105.
3. Efficacy: Baseline and post- operative tidal volumes via incentive spirometry. [ Time Frame: Surgery completion through study completion up to one week. ]
   Baseline and post- operative tidal volumes via incentive spirometry.
4. Efficacy: Minimum and Maximum Pain Scores in both study groups. will be assessed via Numeric Rating Scale 0-10. [ Time Frame: Surgery completion through study completion up to one week. ]
   Minimum and maximum pain scores in both study groups. will be assessed via Numeric Rating Scale 0-10.

Other Outcome Measures:

1. Efficacy:Time to respiratory extubation. [ Time Frame: Cardiovascular intensive care unit arrival until patient is extubated in both groups up to 72 hours. ]
   Time to respiratory extubation.
2. Comparison of hospitalization costs between Group 1 and Group 2. [ Time Frame: Costs of hospitalization from admission to discharge in both groups up to 7 days. ]
   Comparison of hospitalization costs: total length of stay and treatment of gastrointestinal and respiratory complications should they occur in each group.
3. Comparison of medication costs between Group 1 and Group 2. [ Time Frame: Cost of medication from CVICU arrival to hospital discharge in both groups up to 7 days. ]
   Comparison of medication costs will include total opioid medication costs and total cost of IV Acetaminophen and PO Gabapentin in both groups.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient between 18 and 85 years old.
2. Elective or urgent surgery requiring sternotomy approach
3. Subject is able to read and has signed and dated the informed consent document including authorization permitting release of personal health information (PHI) approved by the Inova Institutional Review Board (IRB).

Exclusion Criteria:

1. Patients lacking enteral access on post-operative day 0
2. Inability to communicate
3. Active chronic pain with opioid therapy
4. Active chronic use of gabapentin or pregabaldin
5. Active substance abuse
6. Current self- report of alcoholism
7. End stage renal disease
8. Active renal dialysis therapy

Contacts and Locations

Locations

United States, Virginia

Inova Heart and Vascular institute

Falls Church, Virginia, United States, 22042

Sponsors and Collaborators

Inova Health Care Services

More Information

• Responsible Party: Ramesh Singh, Cardiothoracic Surgeon, Inova Health Care Services
• ClinicalTrials.gov Identifier: NCT03679013
• Other Study ID Numbers: 18-3002
• First Posted: September 20, 2018
• Last Update Posted: August 7, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Ramesh Singh, Inova Health Care Services:

cardiac; surgery; pain

Additional relevant MeSH terms:

Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Acetaminophen; Gabapentin; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antipyretics; Anticonvulsants; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antimanic Agents