Dataset Information

Volume expansion with albumin compared to gelofusine in children with severe malaria: results of a controlled trial.

ABSTRACT:

Objectives

Previous studies have shown that in children with severe malaria, resuscitation with albumin infusion results in a lower mortality than resuscitation with saline infusion. Whether the apparent benefit of albumin is due solely to its colloidal properties, and thus might also be achieved with other synthetic colloids, or due to the many other unique physiological properties of albumin is unknown. As albumin is costly and not readily available in Africa, examination of more affordable colloids is warranted. In order to inform the design of definitive phase III trials we compared volume expansion with Gelofusine (succinylated modified fluid gelatin 4% intravenous infusion) with albumin.

Design

This study was a phase II safety and efficacy study.

Setting

The study was conducted at Kilifi District Hospital, Kenya.

Participants

The participants were children admitted with severe falciparum malaria (impaired consciousness or deep breathing), metabolic acidosis (base deficit > 8 mmol/l), and clinical features of shock.

Interventions

The interventions were volume resuscitation with either 4.5% human albumin solution or Gelofusine.

Outcome measures

Primary endpoints were the resolution of shock and acidosis; secondary endpoints were in-hospital mortality and adverse events including neurological sequelae.

Results

A total of 88 children were enrolled: 44 received Gelofusine and 44 received albumin. There was no significant difference in the resolution of shock or acidosis between the groups. Whilst no participant developed pulmonary oedema or fluid overload, fatal neurological events were more common in the group receiving gelatin-based intervention fluids. Mortality was lower in patients receiving albumin (1/44; 2.3%) than in those treated with Gelofusine (7/44; 16%) by intention to treat (Fisher's exact test, p = 0.06), or 1/40 (2.5%) and 4/40 (10%), respectively, for those treated per protocol (p = 0.36). Meta-analysis of published trials to provide a summary estimate of the effect of albumin on mortality showed a pooled relative risk of death with albumin administration of 0.19 (95% confidence interval 0.06-0.59; p = 0.004 compared to other fluid boluses).

Conclusions

In children with severe malaria, we have shown a consistent survival benefit of receiving albumin infusion compared to other resuscitation fluids, despite comparable effects on the resolution of acidosis and shock. The lack of similar mortality benefit from Gelofusine suggests that the mechanism may involve a specific neuroprotective effect of albumin, rather than solely the effect of the administered colloid. Further exploration of the benefits of albumin is warranted in larger clinical trials.

SUBMITTER: Akech S

PROVIDER: S-EPMC1569382 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature

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Publications

Volume expansion with albumin compared to gelofusine in children with severe malaria: results of a controlled trial.

Akech Samuel S Gwer Samson S Idro Richard R Fegan Greg G Eziefula Alice C AC Newton Charles R J C CR Levin Michael M Maitland Kathryn K

PLoS clinical trials 20060915 5

<h4>Objectives</h4>Previous studies have shown that in children with severe malaria, resuscitation with albumin infusion results in a lower mortality than resuscitation with saline infusion. Whether the apparent benefit of albumin is due solely to its colloidal properties, and thus might also be achieved with other synthetic colloids, or due to the many other unique physiological properties of albumin is unknown. As albumin is costly and not readily available in Africa, examination of more affor ...[more]

PMID: 16998584

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Project description:BackgroundCurrent artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%).Methods and findingsThis randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥ 99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7 g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥ 99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI -7, 5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥ 99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI -12, 1; p = 0.24). Delayed parasite clearance was associated with the N86YPfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms. A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner.ConclusionsA simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children.Trial registrationPan African Clinical Trials Registry PACTR201102000277177.

Project description:Administration of fluids to restore normovolaemia is one of the most common therapeutic interventions performed peri-operatively and in the critically ill, but no study has evaluated the importance of infusion rate for the plasma volume-expanding effect of a resuscitation fluid. The present study is designed to test the hypothesis that a slow infusion of resuscitation fluid results in better plasma volume expansion than a rapid infusion.The study is a single-centre, assessor-blinded, parallel-group, randomised prospective study. Patients over 40 years of age admitted to the post-operative care unit after a Whipple procedure or major gynaecological surgery and presenting with signs of hypovolaemia are eligible for inclusion. Patients are randomised in a 1:1 fashion with no stratification to either rapid (30 minutes) or slow (180 minutes) infusion of 5% albumin at a dose of 10 ml/kg ideal body weight. Plasma volume is measured using 125I human serum albumin at baseline (prior to albumin infusion) as well as at 30 minutes and 180 minutes after infusion start. The primary endpoint is change in plasma volume from baseline to 180 minutes after the start of 5% albumin infusion. Secondary endpoints include the integral of plasma volume over time from baseline to 180 minutes after the start of the infusion and transcapillary escape rate of albumin (%/h) from 180 minutes to 240 minutes after the start of albumin infusion. In addition, diuresis, change in central venous oxygen saturation, lactate and blood pressure will be evaluated. A total of 70 patients will be included in the study, and the study has 80% power to detect a difference of 4 ml/kg in plasma volume expansion between the two groups.The present study is the first clinical investigation of the importance of infusion rate for the plasma volume-expanding effect of a resuscitation fluid.EudraCT identifier: 2013-004446-42 . Registration date: 20 December 2013. ClinicalTrials.gov identifier: NCT02728921 . Registration date: 31 March 2016.

Project description:BACKGROUND:Computerized cognitive rehabilitation training (CCRT) may be beneficial for alleviating persisting neurocognitive deficits in Ugandan severe malaria survivors. We completed a randomized controlled trial of CCRT for both severe malaria and non-malaria cohorts of children. METHODS:150 school-age severe malaria and 150 non-malaria children were randomized to three treatment arms: 24 sessions of Captain's Log CCRT for attention, working memory and nonverbal reasoning, in which training on each of 9 tasks difficulty increased with proficiency; a limited CCRT arm that did not titrate to proficiency but randomly cycled across the simplest to moderate level of training; and a passive control arm. Before and after 2?months of CCRT intervention and one year following, children were tested with the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), computerized CogState cognitive tests, the Behavior Rating Inventory for Executive Function (BRIEF), and the Achenbach Child Behavior Checklist (CBCL). RESULTS:Malaria children assigned to the limited-CCRT intervention arm were significantly better than passive controls on KABC-II Mental Processing Index (P?=?0.04), Sequential Processing (working memory) (P?=?0.02) and the Conceptual Thinking subtest (planning/reasoning) (P?=?0.02). At one year post-training, the limited CCRT malaria children had more rapid CogState card detection (attention) (P?=?0.02), and improved BRIEF Global Executive Index (P?=?0.01) as compared to passive controls. Non-malaria children receiving CCRT significantly benefited only on KABC-II Conceptual Thinking (both full- and limited-CCRT; P?<?0.01), CogState Groton maze chase and learning (P?<?0.01), and CogState card identification (P?=?0.05, full CCRT only). Improvements in KABC-II Conceptual Thinking planning subtest for the non-malaria children persisted to one-year follow-up only for the full-CCRT intervention arm. CONCLUSION:For severe malaria survivors, limited CCRT improved attention and memory outcomes more than full CCRT, perhaps because of the greater repetition and practice on relevant training tasks in the absence of the performance titration for full CCRT. There were fewer significant cognitive and behavior benefits for the non-malaria children, with the exception of the planning/reasoning subtest of Conceptual Thinking, with stronger full- compared to limited-CCRT improvements persisting to one-year follow-up.

Project description:BackgroundOptimal infusion rate of colloids in patients with suspected hypovolemia is unknown, and the primary objective of the present study was to test if plasma volume expansion by 5% albumin is greater if fluid is administered slowly rather than rapidly.MethodsPatients with signs of hypoperfusion after major abdominal surgery were randomized to intravenous infusion of 5% albumin at a dose of 10 ml/kg (ideal body weight) either rapidly (30 min) or slowly (180 min). Plasma volume was measured using radiolabeled albumin at baseline, at 30 min, and at 180 min after the start of infusion. Primary outcome was change in plasma volume from the start of infusion to 180 min after the start of infusion. Secondary outcomes included the change in the area under the plasma volume curve and transcapillary escape rate (TER) for albumin from 180 to 240 min after the start of albumin infusion.ResultsA total of 33 and 31 patients were included in the analysis in the slow and rapid groups, respectively. The change in plasma volume from the start of infusion to 180 min did not differ between the slow and rapid infusion groups (7.4 ± 2.6 vs. 6.5 ± 4.1 ml/kg; absolute difference, 0.9 ml/kg [95%CI, - 0.8 to 2.6], P = 0.301). Change in the area under the plasma volume curve was smaller in the slow than in the rapid infusion group and was 866 ± 341 and 1226 ± 419 min ml/kg, respectively, P < 0.001. TER for albumin did not differ and was 5.3 ± 3.1%/h and 5.4 ± 3%/h in the slow and in the rapid infusion groups, respectively, P = 0.931.ConclusionsThis study does not support our hypothesis that a slow infusion of colloid results in a greater plasma volume expansion than a rapid infusion. Instead, our result of a smaller change in the area under the plasma volume curve indicates that a slow infusion results in a less efficient plasma volume expansion, but further studies are required to confirm this finding. A rapid infusion has no effect on vascular leak as measured after completion of the infusion.Trial registrationEudraCT2013-004446-42 registered December 23, 2014.

Project description:The current guidelines for treatment of malaria include paracetamol to children with fever. No convincing evidence for the beneficial effects of this practice exists. Studies show that time to parasite clearance is significantly longer in children treated with paracetamol, which questions the policy. Whether this is of clinical importance has not been investigated.Children with Plasmodium falciparum monoinfection and ?20 parasites per 200 leucocytes at the Bandim Health Centre, Guinea-Bissau were randomized to receive paracetamol or placebo together with chloroquine for three days in a double blind randomized study. Temperature and symptoms were recorded twice daily during treatment and on day 3. The participants were interviewed and a malaria film taken once weekly until day 35. The data is in the form of grouped failure-times, the outcome of interest being time until parasitaemia during follow-up. Mantel-Haenszel weighted odds ratios are given. Other differences between and within the two groups have been tested using the Chi-square test and Mann-Whitney U test.In the evening of the day of inclusion, the temperature was slightly, but statistically insignificant, higher in the placebo group and significantly more children complained of headache. At no other time was a significant difference in temperature or symptoms detected. However, 6 children from the placebo-group as compared to two children from the paracetamol-group were admitted to hospital with high fever and convulsions by day 3. No differences in the cumulative percentages of children with adequate clinical and parasitological response were found in the intention-to-treat analysis or in the per-protocol analysis.Fewer children had early treatment failure and the mean temperature was slightly lower in the afternoon on day 0 in the paracetamol group. However, the cumulative adequate clinical and parasitological cure rates were not significantly different during the period of study. It is doubtful whether adding paracetamol to the treatment of uncomplicated malaria in children is beneficial.NCT00137566.

Project description:In septic shock, pulse pressure or cardiac output variation during passive leg raising are preload dependence indices reliable at predicting fluid responsiveness. Therefore, they may help to identify those patients who need intravascular volume expansion, while avoiding unnecessary fluid administration in the other patients. However, whether their use improves septic shock prognosis remains unknown. The aim of this study was to assess the clinical benefits of using preload dependence indices to titrate intravascular fluids during septic shock.In a single-center randomized controlled trial, 60 septic shock patients were allocated to preload dependence indices-guided (preload dependence group) or central venous pressure-guided (control group) intravascular volume expansion with 30 patients in each group. The primary end point was time to shock resolution, defined by vasopressor weaning.There was no significant difference in time to shock resolution between groups (median (interquartile range) 2.0 (1.2 to 3.1) versus 2.3 (1.4 to 5.6) days in control and preload dependence groups, respectively). The daily amount of fluids administered for intravascular volume expansion was higher in the control than in the preload dependence group (917 (639 to 1,511) versus 383 (211 to 604) mL, P?=?0.01), and the same held true for red cell transfusions (178 (82 to 304) versus 103 (0 to 183) mL, P?=?0.04). Physiologic variable values did not change over time between groups, except for plasma lactate (time over group interaction, P <0.01). Mortality was not significantly different between groups (23% in the preload dependence group versus 47% in the control group, P?=?0.10). Intravascular volume expansion was lower in the preload dependence group for patients with lower simplified acute physiology score II (SAPS II), and the opposite was found for patients in the upper two SAPS II quartiles. The amount of intravascular volume expansion did not change across the quartiles of severity in the control group, but steadily increased with severity in the preload dependence group.In patients with septic shock, titrating intravascular volume expansion with preload dependence indices did not change time to shock resolution, but resulted in less daily fluids intake, including red blood cells, without worsening patient outcome.Clinicaltrials.gov NCT01972828. Registered 11 October 2013.

Project description:BackgroundPushing Splints 3 (PS3) device was recently introduced for the treatment of Class III malocclusion in children.ObjectivesTo assess the effect on the sagittal maxillary position (SNA, primary outcome) of PS3 therapy compared with rapid maxillary expansion and facemask therapy (RME/FM) and to compare skeletal and dento-alveolar effects in growing Class III patients.Trial designThis trial was a single-centre randomized controlled trial with two groups randomly allocated in a 1:1 ratio of equal size by sealed-envelope randomization, conducted at the Dentistry Unit of Bambino Gesù Children's Hospital, IRCCS (Rome, Italy).MethodsA total of 48 patients with Class III malocclusion were included in the study and randomly allocated to the two groups: PS3 therapy and RME/FM therapy. Only the RME/FM group underwent palatal expansion, and both groups were instructed to wear the appliances 14 hours/day. Pre- (T0) and post-treatment (T1) cephalograms were taken. An independent sample t-test and regression analysis were used to analyse the data (P value <0.05). Researchers involved in statistics and tracings were blinded to the treatment allocation.ResultsA total of 42 patients (21 for each group) completed the study. The maxillary sagittal position improved similarly in both groups (SNA = 0.4°; P = 0.547). A statistically significant decrease of SNPg angle (-1.6°; P < 0.001) and increase of ANPg angle (1.4°; P = 0.018) were found in the RME/FM group compared with PS3 group. CoGoMe angle significantly decreased in RME/FM group compared with PS3 group (-1.7°; P = 0.042). The regression analysis showed an association between SN/MP angle at T0 and the differences between T1 and T0 of SNPg (B = 0.13; P = 0.005) and SN/MP (B = -0.19; P = 0.034). Only three patients (PS3 = 2; RME/FM = 1) had breakages of the devices.LimitationsResults are limited to short-term effects.ConclusionRME/FM therapy and PS3 are both effective therapies for the early correction of Class III malocclusion. The PS3 controlled better mandibular divergency reducing the clockwise rotation in patients with higher mandibular inclination.RegistrationThis study was not registered in a clinical trial registry.

Dataset Information

Volume expansion with albumin compared to gelofusine in children with severe malaria: results of a controlled trial.

Objectives

Design

Setting

Participants

Interventions

Outcome measures

Results

Conclusions

Publications

Volume expansion with albumin compared to gelofusine in children with severe malaria: results of a controlled trial.

Similar Datasets

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