H/A: Dietary Intake (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To assess the evolution of triglyceride levels in HIV-infected patients receiving stable potent antiretroviral therapy treated with n-3 polyunsaturated fatty acids.

Inclusion Criteria:
  • Ambulatory patients of either gender, aged at least 18 years, and presenting with HIV infection treated with stable multiple antiretroviral therapy for at least two months were included in the study if the following criteria were fulfilled:
    • Known and documented hypertriglyceridemia (higher than 3.0g per L) within six months before selection and remaining at least at the same level at the selection visit
    • Baseline triglyceride levels higher than 2.0g per L and less than 10g per L after a four-week triglyceride-lowering diet
  • 10 patients with baseline triglyceride levels higher than 10g per L were not randomized and received n-3 polyunsaturated fatty acids as open treatment. 
Exclusion Criteria:
  • Known hypersensitivity to the active compound or product excipients
  • Pregnancy and breastfeeding
  • Concomitant treatments with a possible influence on the interpretation of results unless treatment had remained unchanged for six months before inclusion
  • Oral antidiabetics and hormonal treatments initiated or modified in the past three months
  • Drugs that induce hepatic metabolism
  • Insulin therapy
  • Lipid-lowering drugs were to have been stopped for more than one month before the selection visit
  • Patients who regularly consumed high levels of alcohol (more than 20g per day) were not included in the study
  • Patients with an abnormal fasting blood glucose level were not included (glycemia higher than 6.6mmol per L).
Description of Study Protocol:

Recruitment

Recruitment methods were not described.

Design

Randomized controlled trial. 

Blinding used

Double-blind 

Intervention

  • After a four-week triglyceride-lowering diet, patients were randomized to either eight weeks of n-3 polyunsaturated fatty acids (two capsules containing 1.0g of fish oil three times daily) or placebo (1.0g of paraffin oil capsules)
  • All subjects received diet counseling in accordance with American Heart Association recommendations (15% to 18% protein, 45% to 55% carbohydrate, 30% to 35% fat) without alcohol consumption
  • Double-blind treatment phase was followed by an eight-week period during which all patients received n-3 polyunsaturated fatty acids plus the diet on an open basis. 

Statistical Analysis

  • 64 patients per group were necessary to identify a 20% difference between treatment groups
  • Primary analysis was performed on the intent-to-treat population
  • Adjusted least square means and the estimated treatment effect were calculated with their corresponding 95% confidence intervals
  • Non-parametric ranked ANCOVA was performed
  • Responders were analyzed using Cochran-Mantel-Haenszel methodology
  • Unadjusted relative risk was estimated, and the adjusted relative risk was calculated independently for each stratification factor
  • Number of patients presenting with adverse events was compared between the two groups using a chi-square test of Fisher exact test
  • Descriptive analyses were used to summarize the incidence rates of events by body system and preferred term. 
Data Collection Summary:

Timing of Measurements

Measurements were taken at screening, before randomization and under treatment at the end of each eight-week period.

Dependent Variables

  • Fasting lipid parameters
  • Percentage of responders
  • Safety issues.

Independent Variables

  • After a four-week diet, patients were randomized to either eight weeks of n-3 polyunsaturated fatty acids (two capsules containing 1.0g of fish oil three times daily) or placebo (1.0g of paraffin oil capsules)
  • An eight-week open-label phase of n-3 polyunsaturated fatty acids followed.

 

 

Description of Actual Data Sample:

Initial N

122 patients, 60 in the n-3 group, 62 in the placebo group. 10 patients were directed to the open n-3 arm of the study. Two dropped out of the PUFA group because they never started the treatment and due to lack of data after randomization, leaving 120 subjects randomized, 58 in the PUFA group and 62 in the placebo group. 90% were male.

Attrition (final N)

11 randomized patients discontinued the study before the end of the double-blind period, five in the PUFA group and six in the placebo group.

Age

Mean age 28 - 69 years

Other Relevant Demographics

  • 25.5% had detectable viral load, mean viral load 3.05 (log)
  • 4% on NRTI only
  • 24% on NRTI + NNRTI
  • 50% on NRTI + PIs
  • 18% on NRTI + NNRTI + PIs
  • 3% on PIs only
  • 2% on NNRTI + PIs.

Anthropometrics

No relevant differences were noted between groups regarding age, gender ratio, history of HIV infection or history of hypertriglyceridemia.

Location

France.

 

Summary of Results:

Key Findings

  • The difference (PUFA vs. placebo) in triglyceride percent change at week eight was -24.6% (range = -40.9% to -8.4%, P=0.0033), the median was -25.5% in the PUFA group vs. 1% in the placebo group and mean triglyceride levels at week eight were 3.4±1.8g per L and 4.8±3.1g per L, respectively
  • Triglyceride levels were normalized in 22.4% of PUFA patients vs. 6.5% of placebo patients (P=0.013) with more than 20% reduction in 58.6% (PUFA) versus 33.9% (placebo) of patients (P=0.007)
  • Under the open-label phase of n-3 PUFAs, the decrease in triglyceride levels was sustained at week 16 for patients in the PUFA group (mean triglyceride, 3.4±1.7g per L), whereas a 21.2% decrease in triglyceride levels occurred for patients in the placebo group (mean triglyceride, 3.3±1.4g per L)
  • No significant differences were observed between groups in the occurrence of adverse events
  • The median triglyceride change at week eight was -43.6% (range, Q1 to Q3; 95% confidence interval, -66.5% to -4.6%) for patients with baseline triglyceride levels higher than 10g per L
  • The difference in mean total cholesterol between groups (PUFA vs. placebo) at week eight was -8.5% (P=0.0117).
Author Conclusion:

This study demonstrated the efficacy of PUFAs to lower elevated triglyceride levels in treated HIV-infected hypertriglyceridemic patients.  N-3 PUFAs have a good safety profile.

Funding Source:
University/Hospital: Institut de Recherche Pierre Fabre
Reviewer Comments:

Recruitment methods were not described. 10 subjects had high triglyceride levels and were not randomized. Questionable representativeness of included subjects.

Quality Criteria Checklist: Primary Research
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? ???
  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? ???
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  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")? N/A
4. Was method of handling withdrawals described? Yes
  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? Yes
  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? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  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? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  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? Yes
  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? Yes
  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? Yes
  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)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  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? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? ???
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes