HF: Carnitine (2007)
Citation:
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To determine the effect on mortality rate and other efficacy parameters of long-term L-carnitine administration for the treatment of heart failure in adults, attributable to dilated cardiomyopathy.
Inclusion Criteria:
- Dilated cardiomyopathy
- Classified as stable (sinus rhythm), according ot the New York Heart Association function class III to IV
- Able to perform treadmill exercise.
Exclusion Criteria:
- Ischemic heart disease (defined as occlusion more than 50%)
- Significant valvular heart disease
- Atrial fibrillation
- Alcohol abuse.
Description of Study Protocol:
- A double-blind placebo-controlled study for the initial three-month period, followed by an unblinded study for the remainder of the three years
- A total of 80 patients were randomly assigned to treatment with L-carnitine or placebo after a baseline hemodynamic study
- All patients received conventional therapy for heart failure that included diuretics, digoxin and angiotensin-converting enzyme inhibitors
- After entering the study, patients were randomly assigned to receive either oral L-carnitine (two g per day) or placebo for three months. The study was unblinded at the end of the three months.
- A Kaplan-Meier survival analysis, presented as a cumulative mortality curve, was used to describe patient death
- The log-rank test was used to compare mortality between the two groups.
Data Collection Summary:
- Hemodynamics were performed during the stabilization phase before patients were entered into the study, at baseline, one month, three months and at approximate six-month intervals throughout the remainder of the three-year study
- Hemodynamic studies included coronary angiography with left ventriculography (entry-only), right catheterization and cardiopulmonary exercise tests, according to the Weber protocol
- Measured parameters included ejection fraction, Weber classification, maximal time of cardiopulmonary exercise test, peak VO2 consumption, arterial and pulmonary blood pressure and cardiac output
- The end point was death at three years, comparing the two groups. The clinical end point was the results of the hemodynamic tests.
Description of Actual Data Sample:
- Mean age of participants in the L-carnitine group (N=42) was 50 years and 48 years in the placebo group (N=38)
- There were 19 males and 23 females in the L-carnitine group vs. 20 males and 18 females in the placebo group
- All participants were residents of Greece
- After a mean of 33.7 months, 70 patients remained in the study: 33 in the placebo and 37 in the L-carnitine group
- Five patients left the study from each group, including one patient in the placebo group who underwent cardiomyoplasty
- Six patients died in the placebo group: Five from pump failure and one from sudden cardiac death
- The one death in the L-carnitine group was from documented sustained ventricular tachycardia despite resuscitation.
Summary of Results:
- There were no statistically significant differences in baseline characteristics between the two groups for the clinical and hemodynamic parameters
- The survival analysis of the remaining 70 subjects showed that the patients' survival was statistically significant in favor of L-carnitime (0≤0.04). The survival rates began to diverge at 12 months. The three-year mortality rate was 18% for the placebo group vs. 3% in the L-carnitine group.
- At three months, there was a statistically significant difference in favor of the L-carnitine patients for the Weber classification, maximal time of cardiopulmonary exercise, peak oxygen consumption, arterial and pulmonary blood pressure and cardiac output
- One patient in the L-carnitine group did not maintain sinus rhythm and had atrial flutter requiring cardioversion
- Seven of the 33 patients in the placebo group had atrial fibrillation which persisted in five; two maintained a sinus rhythm after carioversion and amiodarone treatment.
- Three of the 37 patients who completed the study had minor gastrointestinal problems but were not withdrawn from the study.
Author Conclusion:
- Results suggest that L-carnitine may improve the functional status of patients with moderate to severe heart failure attributable to dilated cardiomyopathy
- A large randomized, placebo-controlled trial is required to fully assess the usefulness of L-carnitine administration in this setting.
Funding Source:
University/Hospital: | University of Athens Medical School (Greece) |
Reviewer Comments:
- Study number is small
- Population is from Greece
- Population is a specific category of heart failure
- Study indicates that 12 months is needed to see differences in mortality rates
- Clinical and hemodynamic results were only for a three-month period, while the mortality results are for three years.
Quality Criteria Checklist: Primary Research
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Relevance Questions | |||
1. | Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) | Yes | |
2. | Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? | Yes | |
3. | Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? | Yes | |
4. | Is the intervention or procedure feasible? (NA for some epidemiological studies) | Yes | |
Validity Questions | |||
1. | Was the research question clearly stated? | Yes | |
1.1. | Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? | Yes | |
1.2. | Was (were) the outcome(s) [dependent variable(s)] clearly indicated? | Yes | |
1.3. | Were the target population and setting specified? | Yes | |
2. | Was the selection of study subjects/patients free from bias? | Yes | |
2.1. | Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? | Yes | |
2.2. | Were criteria applied equally to all study groups? | Yes | |
2.3. | Were health, demographics, and other characteristics of subjects described? | Yes | |
2.4. | Were the subjects/patients a representative sample of the relevant population? | Yes | |
3. | Were study groups comparable? | ??? | |
3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | No | |
3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | Yes | |
3.3. | Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) | Yes | |
3.4. | If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? | N/A | |
3.5. | If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) | N/A | |
3.6. | If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? | No | |
4. | Was method of handling withdrawals described? | No | |
4.1. | Were follow-up methods described and the same for all groups? | Yes | |
4.2. | Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) | Yes | |
4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | Yes | |
4.4. | Were reasons for withdrawals similar across groups? | No | |
4.5. | If diagnostic test, was decision to perform reference test not dependent on results of test under study? | N/A | |
5. | Was blinding used to prevent introduction of bias? | Yes | |
5.1. | In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? | Yes | |
5.2. | Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) | Yes | |
5.3. | In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? | N/A | |
5.4. | In case control study, was case definition explicit and case ascertainment not influenced by exposure status? | N/A | |
5.5. | In diagnostic study, were test results blinded to patient history and other test results? | N/A | |
6. | Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? | No | |
6.1. | In RCT or other intervention trial, were protocols described for all regimens studied? | No | |
6.2. | In observational study, were interventions, study settings, and clinicians/provider described? | N/A | |
6.3. | Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? | Yes | |
6.4. | Was the amount of exposure and, if relevant, subject/patient compliance measured? | No | |
6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | ??? | |
6.6. | Were extra or unplanned treatments described? | Yes | |
6.7. | Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? | Yes | |
6.8. | In diagnostic study, were details of test administration and replication sufficient? | N/A | |
7. | Were outcomes clearly defined and the measurements valid and reliable? | Yes | |
7.1. | Were primary and secondary endpoints described and relevant to the question? | Yes | |
7.2. | Were nutrition measures appropriate to question and outcomes of concern? | Yes | |
7.3. | Was the period of follow-up long enough for important outcome(s) to occur? | Yes | |
7.4. | Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? | Yes | |
7.5. | Was the measurement of effect at an appropriate level of precision? | ??? | |
7.6. | Were other factors accounted for (measured) that could affect outcomes? | Yes | |
7.7. | Were the measurements conducted consistently across groups? | Yes | |
8. | Was the statistical analysis appropriate for the study design and type of outcome indicators? | No | |
8.1. | Were statistical analyses adequately described and the results reported appropriately? | Yes | |
8.2. | Were correct statistical tests used and assumptions of test not violated? | ??? | |
8.3. | Were statistics reported with levels of significance and/or confidence intervals? | Yes | |
8.4. | Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? | No | |
8.5. | Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? | No | |
8.6. | Was clinical significance as well as statistical significance reported? | Yes | |
8.7. | If negative findings, was a power calculation reported to address type 2 error? | N/A | |
9. | Are conclusions supported by results with biases and limitations taken into consideration? | Yes | |
9.1. | Is there a discussion of findings? | Yes | |
9.2. | Are biases and study limitations identified and discussed? | Yes | |
10. | Is bias due to study's funding or sponsorship unlikely? | ??? | |
10.1. | Were sources of funding and investigators' affiliations described? | No | |
10.2. | Was the study free from apparent conflict of interest? | ??? | |