Plain English Summary
Background and study aims
Iron deficiency leading to anemia is a frequent condition in patients following weight-loss surgery. Because of higher effectiveness and fewer side effects than oral supplements, iron is often given in the form of a short infusion in an outpatient setting. It is known that the iron infusion Ferinject can cause a fall in body phosphate through a mechanism not yet fully understood. A fall in phosphate often remains unnoticed, but can potentially lead to serious problems such as heart and respiratory insufficiency. Due to several reasons, patients after weight-loss surgery might be at higher risk for this condition. This study therefore aims to study the frequency and severity of a fall in phosphate one week after a Ferinject infusion as well as associated symptoms, duration and possible risk factors leading to its development in 50 patients following weight-loss surgery.
Who can participate?
Patients aged over 18 after weight-loss surgery who require iron infusion for iron deficiency
What does the study involve?
Patients are asked to join this study during their routine outpatient visit if their iron levels are below a certain range and they are prescribed a Ferinject infusion. Additional to the anyway planned Ferinject infusion, the patient is asked to provide a urine sample and a blood sample from the vein where the infusion is inserted. Ferinject is infused according to the manufacturer’s instructions. Participants are asked to visit the Outpatient Clinic again after one week for another urine and blood sample and a questionnaire investigating possible symptoms of a fall in phosphate. If phosphate stays in normal range, no further visits are planned and study participation ends. If phosphate levels fall below normal range, the patient is asked to attend a further visit another week later for the same procedures. Participants are followed as long as their phosphate is below normal levels up to 12 weeks (to a maximum of 4 additional visits after the first visit). If a severe fall in phosphate occurs, the participant is advised to supplement phosphate (either orally or infused, according to severity).
What are the possible benefits and risks of participating?
There will be no immediate benefit to the participant. However, the results of the study can help to improve care of patients following weight-loss surgery. There will only be the small risk of a blood sample collection (rare: development of a bruise or pain at puncture site, very rare: local infection at of the puncture site).
Where is the study run from?
Kantonsspital St. Gallen (Switzerland)
When is the study starting and how long is it expected to run for?
November 2016 to May 2018
Who is funding the study?
Kantonsspital St. Gallen (Switzerland)
Who is the main contact?
Dr Stefan Bilz
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
BASEC Nr. 2017-00271
Study information
Scientific title
Effect of ferric carboxymaltose on phosphate homeostasis: a prospective cohort study in patients with iron deficiency following bariatric surgery
Acronym
Study hypothesis
The trialists hypothesize that a significant portion of post-bariatric patients receiving parenteral FCM for the treatment of iron deficiency will develop significant hypophosphatemia secondary to enhanced renal losses through a mechanism involving the phosphatonin FGF23. This patient population is at increased risk to develop significant hypophosphatemia due to decreased oral intake, limited enteral resorption and secondary hyperparathyroidism as a predisposing state for hypophosphatemia caused by inadequate calcium intake or Vitamin D insufficiency.
Ethics approval
EKOS: Ethikkommission Ostschweiz, 23/03/2017, BASEC Nr. 2017-00271
Study design
Single-center non-randomized non-interventional prospective clinical trial
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Post-bariatric surgery patients
Intervention
This is a single-center outpatient study with consecutive ongoing recruitment in the Obesity Clinic of the Cantonal hospital St. Gallen in routine consultations of patients after bariatric surgery. Investigators screen for and ask patients with a ferritin level ≤ 30 µg/l prescribed an outpatient infusion of ≥ 500mg FCM as part of routine medical care after bariatric surgery to participate the study.
Blood and urine samples are taken at baseline and at the end of week 1. If hypophosphatemia occurs at the end of week 1, patients are asked to attend another visit at the end of week 2 for the same procedures as at the end of week 1. If hypophosphatemia occurs at the end of week 2, patients are asked to attend another visit at the end of week 4. The same procedures will again be done according to if hypophosphatemia occurs at the previous visit at the end of week 8 and 12.
At each visit, laboratory parameters of phosphate homeostasis (blood and urine) will be measured and possible symptoms of hypophosphatemia will be assessed by a standardized questionnaire. According to the severity of hypophosphatemia, adequate substitution with oral or parenteral phosphate will be initiated.
Intervention type
Other
Phase
Drug names
Primary outcome measure
Proportion of post-bariatric patients developing significant hypophosphatemia, defined as plasma phosphate levels < 0.8 mmol/l one week following the intravenous application of ferric carboxymaltose. Blood samples will be taken from an antecubital vein in a sitting position at Visit 0 (before administration of FCM) and at Visit 1 (one week after FCM). Blood tubes will be sent to central laboratory (ZLM, Cantonal Hospital St. Gallen) where plasma phosphate is measured by standard clinical methods.
Secondary outcome measures
1. Time to recovery from hypophosphatemia following parenteral therapy with FCM in post-bariatric patients, assessed by plasma phosphate levels from blood samples at V2-V5
2. Clinical symptoms associated with the development of hypophosphatemia following parenteral therapy with FCM in post-bariatric patients, assessed by a standardized interview and clinical exam at V0-V5
3. Risk factors leading to the development of hypophosphatemia following parenteral therapy with FCM in post-bariatric patients, assessed using baseline, demographic, clinical and laboratory parameters
4. Pathogenetic mechanisms associated with the development of hypophosphatemia, assessed using baseline demographic and clinical characteristics and parameters of phosphate homeostasis (serum intact and c-terminal FGF 23, PTH, 25 and 1,25 (OH)2 Vitamin D3)
Blood and urine markers of phosphate homeostasis and a standardized interview and clinical exam will be assessed at Visits 0-5. There is a minimum of one follow up visit (V1) one week after the screening visit (V0) and a maximum of 5 follow up visits until 12 weeks after screening visit. If the patient develops hypophosphatemia, discovered at visit 1 (V1), there will be a further visit. Each further visit after V1 will only be held if hypophosphatemia occurs at the previous visit.
Visit windows: visit 1 (V1, week 1) will occur within 7 ± 1 days after the screening visit, which is the visit when FCM is given intravenously. V2 will occur within 7 ± 2 days after V1. Visit 3 (V3, week 4) will occur within 14 ± 2 days after V2. From V3, visit 4 (V4, week 8) should occur within 4 weeks ± 3 days and from V4, visit 5 (V5, week 12) should again occur within 4 weeks ± 3 days.
Overall trial start date
01/11/2016
Overall trial end date
31/05/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age > 18 years
2. Previous bariatric surgery, i.e. Roux-Y-gastric bypass, gastric sleeve resection, biliopancreatic diversion
3. Planned parenteral intravenous iron therapy with ferric carboxymaltose according to local guidelines (serum ferritin < 15 mcg/l or < 30 mcg/l with a previous history of iron deficiency anemia or symptoms compatible with iron deficiency)
4. Written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
50
Participant exclusion criteria
1. Known hypersensitivity to FCM
2. Treatment with intravenous iron within the previous 14 days
3. Glomerular filtration rate < 60 ml/min/1.73m2 (CKD-EPI formula)
4. Plasma phosphate < 0.8 mmol/l at screening
5. Severe Vitamin D deficiency (< 20 nmol/l)
6. 1st trimester of pregnancy
Recruitment start date
05/04/2017
Recruitment end date
01/12/2017
Locations
Countries of recruitment
Switzerland
Trial participating centre
Klinik für Endokrinologie, Diabetologie, Osteologie und Stoffwechselerkrankungen, Kantonsspital St. Gallen
Rorschacherstrasse 95
9007 St Gallen
9007
Switzerland
Funders
Funder type
Hospital/treatment centre
Funder name
Division of Endocrinology and Diabetes, Kantonsspital St. Gallen
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Publication in a high-impact peer reviewed journal covering the field of bariatric/metabolic surgery is intended by June 2018. The original study protocol will be included as supplementary online material.
IPD sharing statement
A full anonymised dataset supporting the findings of this study will be available from Dr Stefan Bilz upon reasonable request.
Intention to publish date
01/06/2018
Participant level data
Available on request
Basic results (scientific)
Publication list