Administración de suplementos de vitamina E en pacientes con fibrosis quística
Referencias
Referencias de los estudios incluidos en esta revisión
Referencias de los estudios excluidos de esta revisión
Referencias de los estudios en curso
Referencias adicionales
Referencias de otras versiones publicadas de esta revisión
Characteristics of studies
Characteristics of included studies [ordered by study ID]
| Study characteristics | ||
| Methods | Randomised controlled study of parallel design with 3 arms. Single‐centre study in UK. Duration 1 month. | |
| Participants | 30 children with CF on pancreatic enzyme supplementation. Age range 6 months to 14.5 years. | |
| Interventions | Acute supplementation and long‐term supplementation. Children received either:
| |
| Outcomes | Serum vitamin E levels and serum RBC haemolysis. | |
| Notes | Acute supplementation (called oral load test in the paper) was only done in 2 participants without controls. The study does not clarify whether the participants were pancreatic sufficient or insufficient. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Not clearly specified in the the paper, states "chosen at random and arbitrarily assigned to one of three groups". |
| Allocation concealment (selection bias) | Unclear risk | Not clearly specified in the the paper. |
| Blinding of participants and personnel (performance bias) | Low risk | Not clearly specified in the the paper. Very likely not blinded, as 1 of arms was no treatment. Objective outcome is measured so absence of blinding unlikely to increase risk of bias. |
| Blinding of outcome assessment (detection bias) | Low risk | Not clearly specified in the the paper. Objective outcome is measured so absence of blinding unlikely to increase risk of bias. |
| Incomplete outcome data (attrition bias) | Low risk | At 1 month reported data for 9 out of 10 participants in fat‐soluble group (i.e. 1 dropout) and for 8 out of 10 participants in water miscible group (i.e. 2 dropouts), no discussions of reasons for dropouts. However, these missing data are unlikely to have a significant impact on the results. |
| Selective reporting (reporting bias) | Unclear risk | Trial protocol not available, but outcomes stated in 'Methods' section reported in 'Results'. |
| Other bias | Unclear risk | Limited information the basis of diagnosis of CF, pancreatic sufficiency/insufficiency etc. |
| Study characteristics | ||
| Methods | Randomised double‐blind placebo‐controlled study of parallel design. Single centre in the USA. Participants stratified according to FEV1 (70% ‐ 85% predicted and > 85% predicted) and use of DNAse. Duration 3 months. | |
| Participants | 40 participants with CF and mild lung disease (FEV1 % predicted > 70%). No details of age or gender split. Evenly distributed to treatment and placebo groups. | |
| Interventions | Participants randomised to take vegetable oil placebo or RRR alpha‐tocopherol (participants < 20 kg = 600 IU/Day < 20 kg; participants > 20 kg = 1200 IU/day). All participants also took ADEKs® for the duration of the study. | |
| Outcomes | Beginnning and end of study: serum vitamin E levels; TNF‐alpha measurements; and IL‐6 measurements. End of study only: liver enzyme levels; PT measurements; and PTT measurements. Adverse effects reported. | |
| Notes | Authors provided full manuscript later, but it did not have much more information. Vitamin E and placebo capsules donated by Henkel Corporation. ADEKs® vitamins and partial financial support provided by Axcan Scandipharm. The study does not clarify whether the participants were pancreatic sufficient or insufficient. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Described as randomized, but method not stated. |
| Allocation concealment (selection bias) | Unclear risk | Not stated. |
| Blinding of participants and personnel (performance bias) | Low risk | Described as double‐blind, but not stated who was blinded. Objective outcome is measured so absence of blinding unlikely to increase risk of bias. |
| Blinding of outcome assessment (detection bias) | Low risk | Described as double‐blind, but not stated who was blinded. Objective outcome is measured so absence of blinding unlikely to increase risk of bias. |
| Incomplete outcome data (attrition bias) | Unclear risk | Implies some dropouts as at end of study 20 participants stated as taking DNAse and 15 as not taking DNAse, but not clearly stated. |
| Selective reporting (reporting bias) | High risk | Protocol later provided by authors but did not provide much more information, no presentation of SD of the effect in the control group. |
| Other bias | Unclear risk | Limited information on the basis for diagnosis of CF. Not clear if pancreatic sufficient or insufficient. |
| Study characteristics | ||
| Methods | Randomised double‐blind placebo‐controlled study of parallel design. Single‐centre trial in the USA. Duration 6 months, planned to see participants every 2 months when possible. No efforts made to counterbalance groups from which individuals were lost during study. | |
| Participants | 49 participants accepted with proven diagnosis of CF and stabilised; 45 children followed for at least 2 months; 37 completed 6 months (18 in treatment group; 19 in placebo group). Each participant rated independently by 2 observers as to condition at the beginning of study on an arbitrary scale (1 = good condition up to 5 = very severe illness). Tocopherol Group Placebo Group | |
| Interventions | 10 mg/kg/day of vitamin E tocopherol (d‐l alpha‐tocopheryl acetate) in water‐miscible solution in 2 or 3 divided doses (n = 20) versus placebo (n = 25). | |
| Outcomes | Weight, muscle power, serum tocopherol, activity of S‐GOT in serum and subjective improvement. | |
| Notes | Reported data at baseline, 2 and 6 months Tocopherol and placebo provided by U.S. Vitamin Corporation. Supported in part by grants from the National Institute of Arthritis and Metabolic Diseases, National Institutes of Public Health, Public Health Service and the Muscular Dystrophy Associations of America. Limited information on the basis for diagnosis of CF. The study does not clarify whether the participants were pancreatic sufficient or insufficient. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation was performed as follows: cards labelled 1 or 2 were individually placed in sealed envelopes in groups of 4 (2 for each mixture number). Envelopes were divided into 3 groups, according to age of participants: < 5 years, 5 ‐ 10 years, and ≥ 10 years and over. Each child accepted into the study group was assigned an envelope from the appropriate age group, and the enclosed card indicated the mixture to be given. |
| Allocation concealment (selection bias) | Low risk | Sealed envelopes with designated randomisation, each child accepted into study was assigned an envelope from the appropriate age group. |
| Blinding of participants and personnel (performance bias) | Low risk | From the paper in plan of study: "Patients and testers did not know which preparation was taken" (double‐blind method) also stated "Physicians blind to vitamin E results". |
| Blinding of outcome assessment (detection bias) | Low risk | Outcome assessors blinded. |
| Incomplete outcome data (attrition bias) | Low risk | Out of the initial 49 participants accepted, 37 completed the study but intention‐to‐treat analysis was not carried out. 3 died within 6 months (all in placebo group), 2 declined to continue medication after 2 months, 1 participant removed due to diabetes mellitus and 7 participants studied for less than 6 months. However, we feel the attrition is balanced among the two groups; hence we judged this study to have a low risk of bias. Planned to measure data at baseline, end of study (6 months) and every 2 months where possible, reported data at baseline, 2 and 6 months. |
| Selective reporting (reporting bias) | Unclear risk | Protocol not available, but the paper reports data for each outcome measurement listed in the 'Methods' section of the paper. |
| Other bias | Unclear risk | None identified. Limited information on the basis for diagnosis of CF and whether pancreatic sufficient or insufficient. |
| Study characteristics | ||
| Methods | Controlled clinical study. Single centre in Canada. Duration 10 ‐ 14 days. | |
| Participants | 22 CF participants admitted for pulmonary infection. | |
| Interventions | Group A: oral fat‐soluble vitamin E 10 mg/kg/day (n = 8). Group B: oral water‐miscible vitamin E (Aquasol E) 10 mg/kg/day (n = 5). Group C: no supplementation (n = 9). | |
| Outcomes | Serum vitamin E levels, alpha‐tocopherol/cholesterol ratio, 3‐day faecal fat excretion. | |
| Notes | All participants also received appropriate intravenous antibiotics, 10% Nutralipid 15 ml/kg/day and usual dosage of enteric‐coated pancreatic enzymes. The study does not clarify whether the participants were pancreatic sufficient or insufficient. Abstract only available. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation not stated, abstract states participants divided into 3 groups. |
| Allocation concealment (selection bias) | Unclear risk | Not stated. |
| Blinding of participants and personnel (performance bias) | Low risk | Not stated, blinding of no treatment compared to either of treatment arms not possible, but not clear if blinded between treatment arms. Objective outcome is measured so absence of blinding unlikely to increase risk of bias. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinding of no treatment compared to either of treatment arms not possible, but not clear if blinded between treatment arms. Objective outcome is measured so absence of blinding unlikely to increase risk of bias. |
| Incomplete outcome data (attrition bias) | Unclear risk | Number of participants recruited and randomized not stated, only numbers of participants for whom results available given. |
| Selective reporting (reporting bias) | Unclear risk | Protocol not available, abstract only so no 'Methods' section available to compare to 'Results' section. |
| Other bias | Unclear risk | None identified. Limited information on the basis for diagnosis of CF and if pancreatic sufficient or insufficient. |
CF: cystic fibrosis
DNAse: dornase alfa
IU: international units
PI: pancreatic insufficient
PS: pancreatic sufficient
PT: prothrombin
PTT: partial thromboplastin time
RBC: red blood cell
SD: standard deviation
S‐GOT: glutamic oxalacetic transaminase
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
| A comparison of two types of vitamin E supplement and not a comparison of vitamin E to control. | |
| Compares bioavailability of preparations, no placebo or control arm. | |
| It is not a study of vitamin E supplementation compared to placebo or control. | |
| Lack of placebo or control group. | |
| Compares two preparations of vitamin E, no control or placebo group. | |
| Compares bioavailability of preparations, no control group. | |
| Not a randomised or quasi‐randomised study. | |
| Comparison of vitamin E given with placebo to vitamin E given with ursodeoxycholic acid in a single participant. | |
| No placebo or control group. Compared 3 preparations of vitamin E to baseline status. | |
| Compared levels of vitamin E after supplementation with 3 different preparations of vitamin E and compared to matched controls. | |
| Compared low‐dose to high‐dose supplements. No placebo or control group. |
Characteristics of ongoing studies [ordered by study ID]
| Study name | STUDY OF THE LONG TERM BIOLOGICAL EFFICACY AND TOLERABILITY OF VEDROP (VITAMIN E‐TPGS FORMULATION) AFTER DAILY ORAL ADMINISTRATION IN 30 PAEDIATRIC PATIENTS WITH CYSTIC FIBROSIS ‐ 1ORP2 |
| Methods | Interventional clinical trial of medicinal product |
| Participants | Less than or equal to 15 years with Cystic fibrosis |
| Interventions | d‐a‐tocopheryl PEG 1000 succinate |
| Outcomes | The patient clinical and biological status; |
| Starting date | 25/04/2007 |
| Contact information | |
| Notes | trial ongoing |
Data and analyses
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Serum vitamin E levels Show forest plot | 3 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.1  Comparison 1: Water‐miscible vitamin E supplementation versus control, Outcome 1: Serum vitamin E levels | ||||
| 1.1.1 Up to 1 month | 2 | 32 | Mean Difference (IV, Fixed, 95% CI) | 17.66 [10.59, 24.74] |
| 1.1.2 Up to 3 months | 1 | 45 | Mean Difference (IV, Fixed, 95% CI) | 11.61 [4.77, 18.45] |
| 1.1.3 Up to 6 months | 1 | 45 | Mean Difference (IV, Fixed, 95% CI) | 19.74 [13.48, 26.00] |
| 1.2 Weight Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Analysis 1.2  Comparison 1: Water‐miscible vitamin E supplementation versus control, Outcome 2: Weight | ||||
| 1.2.1 Up to 3 months | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 1.2.2 Up to 6 months | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Serum vitamin E levels Show forest plot | 3 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 2.1  Comparison 2: Fat‐soluble vitamin E supplementation versus control, Outcome 1: Serum vitamin E levels | ||||
| 2.1.1 Up to 1 month | 2 | 36 | Mean Difference (IV, Fixed, 95% CI) | 13.59 [9.52, 17.66] |
| 2.1.2 Up to 3 months | 1 | 36 | Mean Difference (IV, Fixed, 95% CI) | 6.40 [‐1.45, 14.25] |
Study flow diagram
Comparison 1: Water‐miscible vitamin E supplementation versus control, Outcome 1: Serum vitamin E levels
Comparison 1: Water‐miscible vitamin E supplementation versus control, Outcome 2: Weight
Comparison 2: Fat‐soluble vitamin E supplementation versus control, Outcome 1: Serum vitamin E levels
| Water‐soluble vitamin E compared with control for cystic fibrosis | ||||||
| Patient or population: children and adults with cystic fibrosis Settings: outpatients Intervention: 10 mg/kg/day of oral vitamin E tocopherol (d‐l alpha‐tocopheryl acetate) in water‐miscible solution Comparison: no supplementation (Harries 1969; Wong 1988) or placebo (Levin 1961) | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| No supplementation or placebo | Water‐soluble oral vitamin E | |||||
| Vitamin E total lipid ratio | This outcome was not measured. | |||||
| Vitamin E levels in serum: umol/L Follow‐up: 6 months | The mean serum level of vitamin E in the control group was 4.6 umol/L. | The mean serum level of vitamin E in the intervention group was 19.74 umol/L higher (13.48 umol/L higher to 26.00 umol/L higher). | MD 19.74 (13.48 to 26.00). | 45 | ⊕⊕⊝⊝ | Only 1 study reported this outcome at the 6‐month time point ( Levin 1961 ). 2 further studies reported serum levels of vitamin E at 1 month and found a statistically significant result in favour of the supplemental group, MD 17.66 (95% CI 10.59 to 24.74) (Harries 1969; Wong 1988). |
| Neuropathy due to vitamin E deficiency | This outcome was not measured. | |||||
| Retinopathy due to vitamin E deficiency | This outcome was not measured. | |||||
| BMI | This outcome was not measured. | |||||
| Height | This outcome was not measured. | |||||
| FEV1 % predicted: change from baseline | This outcome was not measured. | |||||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| a. Downgraded once becasue of indirectness in the data. The single study reporting at 6 months included only children and therefore the effect on adults is unknown. b. Downgaded once due to imprecision resulting from small numbers of participants (n = 45). | ||||||
| Fat‐soluble vitamin E compared with control for cystic fibrosis | ||||||
| Patient or population: children and adults with cystic fibrosis Settings: outpatients Intervention: fat‐soluble vitamin E 10 mg/kg/day in 2 trials (Harries 1969; Wong 1988); participants < 20 kg = 600 IU/Day < 20 kg; participants > 20 kg = 1200 IU/day in 1 trial (Keljo 2000) Comparison: no supplementation (Harries 1969; Wong 1988) or placebo (Keljo 2000) | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| No supplementation or placebo | Fat‐soluble oral vitamin E | |||||
| Vitamin E total lipid ratio | This outcome was not measured post‐intervention. | |||||
| Vitamin E levels in serum: umol/l Follow‐up: six months | None of the trials measured this outcome at the 6‐month time point. | 2 studies reported serum levels of vitamin E at 1 month and found a statistically significant result in favour of the supplemental group, MD 13.59 (95% CI 9.52 to 17.66) (Harries 1969; Wong 1988). 1 study reported serum levels of vitamin E at 3 months and found no statistically significant difference between intervention and control, MD 6.40 (95% CI ‐1.45 to 14.25) (Keljo 2000). | ||||
| Neuropathy due to vitamin E deficiency | This outcome was not measured. | |||||
| Retinopathy due to vitamin E deficiency | This outcome was not measured. | |||||
| BMI | This outcome was not measured. | |||||
| Height | This outcome was not measured. | |||||
| FEV1 % predicted: change from baseline | This outcome was not measured. | |||||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Serum vitamin E levels Show forest plot | 3 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.1.1 Up to 1 month | 2 | 32 | Mean Difference (IV, Fixed, 95% CI) | 17.66 [10.59, 24.74] |
| 1.1.2 Up to 3 months | 1 | 45 | Mean Difference (IV, Fixed, 95% CI) | 11.61 [4.77, 18.45] |
| 1.1.3 Up to 6 months | 1 | 45 | Mean Difference (IV, Fixed, 95% CI) | 19.74 [13.48, 26.00] |
| 1.2 Weight Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 1.2.1 Up to 3 months | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 1.2.2 Up to 6 months | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Serum vitamin E levels Show forest plot | 3 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 2.1.1 Up to 1 month | 2 | 36 | Mean Difference (IV, Fixed, 95% CI) | 13.59 [9.52, 17.66] |
| 2.1.2 Up to 3 months | 1 | 36 | Mean Difference (IV, Fixed, 95% CI) | 6.40 [‐1.45, 14.25] |
