Clinical trial NCT03449693: Efficacy of Oral Supplementation With Magnesium to Reduce Febrile Neutropenia
Official title: Efficacy of Oral Supplementation With Magnesium to Reduce Febrile Neutropenia in Pediatric Oncology Patients Treated With Cisplatin-Based Chemotherapy: Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Febrile Neutropenia
Lead sponsor: Universidad Nacional Autonoma de Mexico
Sponsor class: OTHER
Collaborators: name: Hospital Infantil de Mexico Federico Gomez
name: Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional
First posted: 2018-02-28
Enrollment: 214
Sex: ALL
Minimum age (years): 9
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two groups: Intervention group and control group. The intervention group will receive institutional care protocol plus oral supplementation with magnesium. The control group will receive institutional care protocol only.
Primary purpose: PREVENTION

Brief summary: Clinical Trial. Open label. Parallel Groups. The purpose of the study is to determine the efficacy of oral supplementation with magnesium oxide to reduce febrile neutropenia episodes in pediatric oncology patients treated with cisplatin-based chemotherapy.

Detailed description: Febrile neutropenia (FN) is a worrying outcome in children receiving chemotherapy because it increments the risk of major complications, reduces quality of life and increments treatment costs. Moreover, it is the most common diagnosis in pediatric oncology patients that enter emergency rooms and the second most important cause of hospitalization, just behind hospitalization for administration of chemotherapy.

In Mexico, incidence of FN is of 62% of children with solid tumors treated with cisplatin-based chemotherapy (CBC). Cisplatin is one of the most nephrotoxic drugs being used in clinical settlements. The assessment of nephrotoxicity is made with the manifestation of tubular damage that causes electrolyte losses, specially of magnesium. Recently, our investigation group reported that there is an association of hypomagnesemia and the apparition of FN. This association has a biologic explanation in the fact that magnesium is a necessary cofactor for the neutrophil's diapedesis and the activation of complement cascade. To our knowledge, the role of magnesium supplementation has not been explored. With this evidence in mind, the investigators wondered if oral supplementation with magnesium will reduce FN episodes in pediatric oncology patients treated with CBC.

Objective: Determine the efficacy of oral supplementation with magnesium to reduce FN episodes in pediatric oncology patients treated with CBC.

Hypothesis: Previous clinical trials made in adult population have reported that supplementation with magnesium salts reduce episodes of hypomagnesemia in between 13 and 50%. Thus, oral supplementation with magnesium oxide will reduce 20% of FN episodes in pediatric oncology patients treated with CBC.

Materials and Methods: Randomized Clinical Trial, open-label, parallel groups of children over the age of nine with solid tumors treated with CBC at the Haemato-Oncology Department of the Hospital Infantil de México. To prove the hypothesis, it is required to randomize 107 CBC cycles to the intervention group and 107 CBC cycles to the control group. The sample size calculation was made by using the two proportions formula. Randomize of children will be made when they receive CBC indication. Patients assigned to the intervention group will receive institutional attention protocol plus a bottle of magnesium oxide, at the moment of hospitalization discharge. Patients assigned to the control group will receive only institutional attention protocol. The follow-up of patients will be made until an episode of FN appears or until the patient comes back for another CBC cycle. FN assessment will be measured with a unique temperature \>38.3°C or a sustained temperature \>38°C over the course of an hour plus a count of neutrophils under 1000 cells/mm3. The efficacy of oral supplementation with magnesium oxide will be determined by a Relative Risks calculation with confidence interval of 95% (CI95%). Moreover, Absolute Risk Reduction will be calculated, as well as Necessary Number to Treat. To adjust the principal variable a multivariate analysis will be made with a multiple logistic regression. The analysis will be made by protocol and by intention to treat.

Eligibility criteria: Inclusion Criteria:

* Pediatric patients \> 9 years old
* Pediatric patients with solid tumors treated with cisplatin-based chemotherapy
* Signing of Informed Consent from the parents
* Signing of Informed Assent from the children

Non-inclusion Criteria:

* Patients whose parents do not sign the Informed Consent
* Patients with magnesium losing tubulopathy
* Patients with hypomagnesemia previous to the cisplatin-based chemotherapy

Exclusion Criteria:

- Patients whose parents retire the Informed Consent

Primary outcomes:
measure: Febrile Neutropenia
timeFrame: After randomization until day 30
Secondary outcomes:
measure: Time passed from cisplatin-based chemotherapy until the apparition of febrile neutropenia
timeFrame: After randomization until day 30
measure: Safety of Oral Supplementation with Magnesium
timeFrame: Evaluate the apparition of adverse effects of oral supplement of magnesium oxide Time Frame: After randomization until day 30
measure: Hypomagnesemia
timeFrame: After randomization until day 30
Other outcomes:
Locations:
city: Cuauhtémoc
country: Mexico
facility: Hospital Infantil de Mexico Dr. Federico Gomez
state: Ciudad De México
Study officials:
affiliation: Universidad Nacional Autónoma de México. Facultad de Estudios Superiores Zaragoza
name: Osvaldo D Castelán, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Infantil de México Dr. Federico Gómez
name: Miguel A Palomo, PhD
role: PRINCIPAL_INVESTIGATOR
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