Safety Study of Octreotide Injection to Prevent GI Bleeding in Patients With Left Ventricular Assist Device (LVAD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Virginia Commonwealth University
Sponsor:
Collaborators:
Thoratec Corporation
Novartis
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01707225
First received: October 11, 2012
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

The investigators hypothesize that octreotide LAR (Long Acting Release) safely decreases GI bleeding in patients with a left ventricular assist device (LVAD). Patients undergoing implantation of non-pulsatile, continuous-flow LVAD have a higher incidence of gastrointestinal bleeding. This is a significantly associated morbidity and can threaten a patient's life as well as their ability to undergo eventual heart transplantation secondary to both general health/strength and the potential development of antibodies to blood products that would make future transfusions and transplantations more difficult.

If this research finds that use of octreotide LAR can decrease the incidence of gastrointestinal bleeding in this patient population, it will revolutionize the manner in which these patients are managed. The finding of reduced GI bleeding would allow the patient to have less exposure to blood products, reduce hospitalizations, and ensure that subsequent transplant planning not be delayed. This would not only be of great benefit to the patient, but would significantly decrease health-care costs through preventive measures.

The goal of this project is to study whether the regular administration of monthly octreotide LAR is safe and if it will decrease the incidence of gastrointestinal bleeding in patients undergoing implantation of non-pulsatile, continuous flow left ventricular assist devices (LVAD).


Condition Intervention Phase
Gastrointestinal Bleeding
Drug: Octreotide LAR Depot
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Octreotide LAR Depot in Left Ventricular Assist Device (LVAD) Associate Gastrointestinal (GI)

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • The primary specific aim is to determine the safety of octreotide LAR in patients with a LVAD. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Patient experience of certain cardiovascular, CNS, dermatologic, endocrine and metabolic, GI, Hematologic, Neurologic, renal, and respiratory symptoms will be recorded throughout the study


Secondary Outcome Measures:
  • Our key secondary outcomes will focus on study drug efficacy. Patient experience of the following will be assessed: Need for Blood Transfusion Hospital Admission for GI Bleed [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: February 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Octreotide LAR Depot
Once enrolled in the study subjects will receive a monthly intra-muscular injection of 20mg of octreotide LAR at each study visit for 24 weeks and will be followed for a total of 36 weeks.
Drug: Octreotide LAR Depot
The subject will be seen in clinic every 4 weeks (+/- 4 days) through week 24. During weeks 25-36 the subject will receive a telephone call every 4 weeks +/- 4 days, from the research nurse to assess for changes occurring after the study drug was stopped. Subjects will receive a physical exam and interview at each visit to assess for any sign of GI bleeding at home as per standard protocol for HeartMate II patients and for potential drug related side effects. Labs collected for research will include monthly basic metabolic panel (BMP), complete blood count (CBC), fructosamine and quarterly HGbA1C , VEGF, vWF, vWF activity assay, thyroid stimulating hormone (TSH), platelet function test and fibrinogen. Subjects will receive their monthly injection while in clinic for their every 4 weeks appointment. The subjects will be followed and data will be collected for 36 weeks, or for as long as they are enrolled in the study.

  Hide Detailed Description

Detailed Description:

The primary specific aim is to determine the safety of octreotide LAR in patients with a LVAD.

Patient experience of the following will be assessed throughout the study (list obtained from up-to-date.com)

Cardiovascular:

Sinus bradycardia (19% to 25%) Hypertension (≤13%) conduction abnormalities (9% to 10%)

Central nervous system:

Fatigue (1% to 32%) headache (6% to 30%) malaise (16% to 20%) fever (16% to 20%) dizziness (5% to 20%) Pain (4% to 15%)

Dermatologic:

Pruritus (≤18%) Rash (15%; depot formulation) alopecia (≤13%)

Endocrine & metabolic:

Hyperglycemia (2% to 27%)

Gastrointestinal:

Abdominal pain (5% to 61%) loose stools (5% to 61%) nausea (5% to 61%) diarrhea (34% to 58%) flatulence (≤38%) cholelithiasis (13% to 38%; length of therapy dependent) constipation (9% to 21%) vomiting (4% to 21%)

Hematologic Anemia (5-15%)

Local:

Injection site pain (2% to 50%; dose and formulation related)

Neuromuscular & skeletal:

Back pain (1% to 27%) arthropathy (8% to 19%) myalgia (≤18%)

Renal Kidney Stones (5-15%)

Respiratory:

Upper respiratory infection (10% to 23%)

Miscellaneous:

flu symptoms (1% to 20%)

Our key secondary outcomes will focus on study drug efficacy. Patient experience of the following will be assessed:

Need for Blood Transfusion Hospital Admission for GI Bleed

Heart disease is a leading cause of death and disability, according to the American Heart Association. Current therapies include lifestyle modification, medical management and revascularization via Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Surgery (CABG). However, a large portion of patients develop cardiomyopathy which is refractory to the above interventions. They are treated with chronic inotropes, resynchronization and other forms of medical management.

Many of these patients eventually worsen and need consideration for cardiac transplantation. The Thoratec Heartmate II, which is the primary left ventricular assist device (LVAD) implanted at our institution, has been used as a bridge-to-transplantation. More recently it has been approved as destination therapy for patients who are not candidates for transplantation. Over 6000 of these devices have been implanted worldwide since their introduction. We have implanted over 70 here at the VCU Health System and the McGuire VA Medical Center.

The early LVAD devices provided physiologic pulsatility, but were large in size and required large catheters for external venting. The newer continuous flow LVAD devices, such as the Heartmate II, offer the benefit of being smaller and easier to implant as well as improving mobility and thus quality of life. However, this benefit comes with a complication of an increased incidence of GI bleeding, thought to be related to the loss of pulsatility and the nature of these smaller devices.

Approximately 10-30% of patients experience at least one episode GI bleeding which is likely multifactorial. It has already been demonstrated that an acquired von Willebrand Syndrome (vWS) develops due to destruction of multimeric vWF. Additionally, it has been shown that these patients have a higher than normal percentage of gastrointestinal angiodysplasia. Whether these are preexisting or develop as a result of de novo angiogenesis from the gut mucosa is unknown. It is thought that the loss of pulsatility and potential hypoxia result in secretion of angiogenic mediators and contribute to the development of angiodysplasia.

Current treatment for LVAD associated GI bleeding is aimed at identifying the location of bleeding and treatment with blood product transfusion, cryoprecipitate for vWS, Desmopressin for platelet dysfunction, and interventions through Interventional Radiology (IR) and surgery. In addition to the obvious costs and increase in morbidity and mortality associated with the above therapies, patients who receive multiple transfusions develop antibodies and thus become more difficult to transplant. Thus a vicious cycle develops.

We need to strive for a proactive stance in these patients and attack the problem at the source. There is a considerable amount of experience using octreotide in idiopathic chronic GI bleeding. This is likely due to its ability to decrease splanchnic blood flow and its potential ability to inhibit angiogenesis. Octreotide has been thoroughly studied and has a known safety profile. Off label use of octreotide LAR for the purpose of attenuating LVAD associated GI bleeding is currently practiced by some physicians at VCU with no adverse side effects encountered. It is time to formally study the safety and efficacy of octreotide LAR for this purpose. We propose an open-label safety study for 10 subjects to be followed for a total of 24 weeks. Should the safety study be favorably completed, a multi-center trial with randomization to octreotide LAR or placebo with endpoints of GI bleeding and transfusion will be pursued.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • LVAD insertion as bridge to transplant or destination
  • 18 years of age or older

Exclusion Criteria:

  • Poorly controlled diabetes, A1C greater than 8%
  • Poorly controlled hypothyroidism, TSH > upper limit of normal (5.5)
  • End Stage Renal Disease (ESRD) requiring dialysis
  • Cirrhosis
  • Anemia (Hgb < 8)
  • Acromegaly
  • Hx of chronic diarrhea - as determined by history of loose stool lasting longer than 2-4 weeks
  • Pregnancy or breastfeeding
  • Inability to provide informed consent
  • Incarceration or otherwise a ward of the state
  • Non-English speaking
  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: NCT01707225

Contacts
Contact: Christine DeWilde, RN 804-628-5710 dewildect@vcu.edu

Locations
United States, Virginia
Virginia Commonwealth University Health System Recruiting
Richmond, Virginia, United States, 23298
Contact: Rajiv Malhotra    804-828-9071      
Contact: Chris DeWilde, RN    804-628-5710    dewildect@vcu.edu   
Sponsors and Collaborators
Virginia Commonwealth University
Thoratec Corporation
Novartis
Investigators
Principal Investigator: Rajiv Malhotra, DO MS VCU
  More Information

No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01707225     History of Changes
Other Study ID Numbers: HM14516
Study First Received: October 11, 2012
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Virginia Commonwealth University:
GI Bleeding
Gastrointestinal bleeding
LVAD

Additional relevant MeSH terms:
Gastrointestinal Hemorrhage
Hemorrhage
Gastrointestinal Diseases
Digestive System Diseases
Pathologic Processes
Octreotide
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 22, 2014