"Which of three different doses of L-carnitine administered via IV, is effective in helping people with sepsis?"
18 to 100 years old
Drug study, Phase 2
We are doing this study to determine if one of three doses of L-carnitine is effective in helping people with sepsis. L-carnitine is a nutrient, like a vitamin, that is in everyone’s normal diet and body and it helps the cells make energy. When people get really sick, they lose L-carnitine in their urine and the cells have difficulty making energy.
This study requires
If you agree to be in this study, you will receive the standard medications used to treat sepsis. These treatments typically include antibiotic medication, fluids given through an I.V. and occasionally blood product transfusions. You will also be randomized, by chance like the flip of a coin, to receive one of three doses of L-carnitine or a placebo for 12 hours. A placebo looks like the study drug but does not have medicine in it. Neither you nor the study doctor will choose what treatment you receive. The randomization will change during the study so that study participants will be more likely to receive the dose of L-carnitine that is working the best. If one of the three doses of L-carnitine is doing very poorly, new participants will not receive that dose of L-carnitine. L-carnitine is approved by the Food and Drug Administration (FDA), but the way we are using it is experimental. Neither you, the research team, nor your treating doctor will know if you are receiving the drug or placebo.
A heart tracing (EKG) will be obtained from your records. If you do not have one, we will order one for you. You will not be charged for the EKG.
You will have a brief physical exam at enrollment, and again at 12 hours, 24 hours, and 48 hours.
You may have a video microscopy (a video of the blood flow under the tongue) done twice. Once before and once after the L-carnitine or placebo is administered. This is similar to having your temperature taken with a thermometer under your tongue. The video is not dangerous, but some people find it mildly uncomfortable.
We will draw a total of 15 tablespoons of blood during the first 4 days of your participation: · 3 tablespoons before the L-carnitine or placebo is administered · 3 tablespoons 12 hours after the L-carnitine or placebo is administered · 3 tablespoons 24 hours after the L-carnitine or placebo is administered · 3 tablespoons 48 hours after the L-carnitine or placebo is administered · 3 tablespoons 72 hours after the L-carnitine or placebo is administered
We will use the blood to determine your body’s response to infection. We will also look at the DNA for different proteins that might affect the body’s response to L-carnitine. In the future, some of the blood may be used to learn more about the body’s reaction to infection. Some of the blood may be sent to other institutions for this testing, but no information that could identify you will be sent with the samples.
We will review your medical records from the course of your hospital stay. In 28 days, we will contact you by phone to determine your health status. We will check the Social Security Death Index (SSDI) and medical records at 3, 6, and 12 months to see if you are still alive after the study. Your participation in this study will last for one year.
You will interact only with approved study investigators or other approved research personnel during this study. All study related testing, treatment and examinations will be performed at the U.C. Davis Medical Center. Study personnel may contact you by telephone to arrange necessary follow up examinations and conduct follow up interviews.
Who can participate?
1. Suspected or confirmed infection (examples include but are not limited to: white cells in a normally sterile body fluid; perforated viscus; radiographic evidence of pneumonia in clinical symptoms; a syndrome associated with a high risk of infection e.g. cellulitis, cutaneous abscess, ascending cholangitis, toxic shock syndrome, fever of unknown origin with high suspicion of infectious etiology)
2. Any two of four criteria of systemic inflammatory response as defined by the 2001 ACCP/SCCM Consensus Conference Committee;
3. Recognition of septic shock and initiation of quantitative resuscitation within 24 hours of enrollment;
4. Requirement of high dose vasopressors for ≥4 hours to treat shock: Norepinephrine > 0.05mcg/kg/min; dopamine >10mcg/kg/min; Phenylephrine >0.4 mcg/kg/min; epinephrine > 0.05 mcg/kg/min;
5. Cumulative sequential organ failure assessment (SOFA) score of ≥ 6;
6. Blood lactate level of >2.0 mMol/L.
1. Age <18 years;
2. Pregnancy or breastfeeding;
3. Any primary diagnosis other than sepsis;
4. Established Do Not Resuscitate status or advanced directives restricting aggressive care or treating physician deems aggressive care unsuitable;
5. Any history of seizures or a known seizure disorder;
6. Any known inborn error of metabolism;
7. Anticipated requirement for surgery that would interfere with the 12 hour infusion time;
8. Active participation in another interventional study;
9. Cardiopulmonary resuscitation (chest compression or defibrillation) prior to enrollment;
10. Known systemic allergy to L-carnitine.
11. Severe immunocompromised state (e.g. subject has neutropenia [receiving cytotoxic chemotherapy with absolute neutrophil count <500/uL or expected to decline to < 500 uL within the next three days).
12. Active Treatment with Coumadin
Benefits and risks of participating
This study may or may not improve your condition. We cannot promise any benefits to you or others from your taking part in this research. However, possible benefits include improvement in recovery from sepsis. The information gained from your case may benefit others with your condition in the future
Potential risks associated with participating in this study include:
Blood Draw: · Pain · Infection · Bleeding · Bruising L-Carnitine Likely: · Nausea Less Likely: · Abdominal cramping, diarrhea, or a body odor.
Rare but Serious: · Allergic reactions may range from minor itching to rash to major reactions, which can result in death. · Increased INR levels for patients taking warfarin (Coumadin) · Seizure We do not know how the body might respond to the medications or procedures used in this study. We will discuss the risks identified above with you and the chances that they will happen. There may be risks that we do not know about at this time. In addition to these risks, this research may hurt you in ways that are unknown. These may be a minor inconvenience or may be so severe as to cause death.
The risks of L-Carnitine to an unborn child are unknown. Women who are pregnant will not be included in this study.
Any medical or personal data collected for this study will be retained in a secured manner. However, there is a risk that personal data collected for this study could be lost or stolen.