Developing Individualized Strategies to Prevent Nausea and Vomiting (PDNVF)

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01393288
First received: July 11, 2011
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

Every year, more than 5 million patients in the US experience postoperative nausea and/or vomiting (PONV) and in the ambulatory setting post-discharge nausea and/or vomiting (PDNV) is the most common cause for unanticipated hospital re-admissions. Similarly, millions of patients suffer from chemotherapy induced nausea and/or vomiting (CINV), and one out of five patients discontinues chemotherapy for this reason. Thus, the control of nausea and vomiting remains a major health concern for the investigators society. The investigatorsoverall goal is to further the understanding of nausea and vomiting and optimize antiemetic selection in order to facilitate individualized patient care.

Unfortunately, current antiemetics reduce the incidence of nausea by only about one third. As a result, antiemetics are often combined, exposing patients to adverse events and drug interactions without evidence for the most effective combination. Moreover, it remains unclear why such a large amount of inter-individual variability exists in antiemetic responsiveness. 5HT3, NK1, and GABA receptors are targets for some of the most commonly prescribed anti-emetics. Furthermore, these receptors have many known genetic polymorphisms, including several linked to incidence of nausea and vomiting. Thus pharmacogenomic variation may in part explain interindividual differences in treatment responses and will be tested in this proposal.

Leveraging the established infrastructure of the UCSF Clinical and Translational Science Institute, and the support of 6 patient recruitment sites, the investigators will enroll 1280 high risk patients to three oral interventions with distinct mechanisms of action for nausea and vomiting. Investigating nausea and vomiting in ambulatory surgical patients is an excellent model for this trial owing to a high incidence, short observational period, and the ability to standardize and control potentially confounding variables. In this proposal, 100% of patients will receive a single intraoperative dose of 4 mg ondansetron, which is similar to the 80% of patients who receive prophylaxis in common practice. Using a factorial design, these patients will be randomized to receive one out of eight possible combinations of the three interventions (ondansetron, aprepitant, lorazepam) versus placebo (ond+aprep+lora, ond+aprep, ond+lora, aprep+lora, ond, aprep, lora, or placebo). Thus, in this proposal 87.5% (7 out of 8 patients) will have antiemetic coverage for the postdischarge period, which is considerably higher than in common practice, where only 4% of patients have antiemetic coverage after discharge. The primary endpoint will be the prevention of nausea and vomiting within 48 hours after ambulatory surgery. The advantage of the factorial trial design is its high efficiency to systematically investigate multiple interventions while allowing us to test for potential interactions. It is also an ideal format for the simultaneous assessment of pharmacogenomic interactions of antiemetics in this proposal.

To this end, the investigators will collect DNA samples and take advantage of the unique opportunity to investigate the effects of variation in candidate receptor genes in the context of the three treatment interventions for PDNV. This approach may in part explain inter-individual differences in drug efficacy and allow for future screening of at-risk patients. Specifically, the investigators will be assessing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of targeted receptors for the antiemetics tested.

Aim 1: To determine efficacy of three interventions for the prevention of PDNV.

Hypothesis 1.1: Each intervention reduces the incidence of PDNV.

Hypothesis 1.2: Efficacy of all interventions is independent so that efficacy of a combination can be derived from the efficacy of the individual interventions.

Aim 2: To determine if drug response for anti-emetics is dependent upon genetic variance.

Hypothesis 2: Efficacy of ondansetron, aprepitant and lorazepam to reduce PDNV differs with 5HT3, NK1, and GABA receptor gene variation, respectively.


Condition Intervention
Postoperative Nausea and Vomiting
Genetic Polymorphisms
Drug: Ondansetron
Drug: Lorazepam
Drug: Aprepitant

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Developing Individualized Strategies to Prevent Nausea and Vomiting

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Incidence of post-discharge nausea and vomiting (PDNV) [ Time Frame: 48 hours post-discharge ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: November 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Ondansetron Drug: Ondansetron
8 mg ondansetron ODT or placebo, 1 hour pre-operatively, before discharge, evening of day of surgery, morning of postoperative day (POD) 1, lunch POD 1, evening POD 1, and morning of POD 2
Placebo Comparator: Lorazepam Drug: Lorazepam
1 mg Lorazepam or placebo 1 hour preoperatively, before discharge, evening of day of surgery, morning of postoperative day (POD) 1, lunch of POD 1, evening of POD 1, and morning of POD 2.
Placebo Comparator: Aprepitant Drug: Aprepitant
40 mg Aprepitant or placebo 1 hour preoperatively and before discharge (placebo for postoperative days 1-2)

  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult (i.e. at least 21 years of age) ambulatory surgery patients, with a duration of 1-4 hours
  • able to understand, read, and write in English, are ASA physical status 1-3, and are high risk PDNV patients (with 3 or more of the following risk factors:
  • female gender
  • age < 50
  • history of PONV and/or currently prone to motion sickness, and expectation of post-op opioid use).

Exclusion Criteria:

  • patients not at high risk for PDNV (as described above)
  • patients <21 years of age
  • planned inpatient surgical patients
  • planned total intravenous anesthesia, sedation, or regional technique without inhaled anesthetic
  • inability to provide informed consent in English
  • pregnant or breastfeeding
  • persistent and/or current nausea/vomiting.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01393288

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94115
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Kentucky Hospital
Lexington, Kentucky, United States, 40506
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02215
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01393288     History of Changes
Other Study ID Numbers: 1R01CA163074-01A1, 10831533
Study First Received: July 11, 2011
Last Updated: November 12, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Nausea
Vomiting
Postoperative Nausea and Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Postoperative Complications
Pathologic Processes
Lorazepam
Ondansetron
Aprepitant
Fosaprepitant
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipruritics

ClinicalTrials.gov processed this record on August 26, 2014