Optimizing iron suppletion after Roux-en-Y Gastric Bypass

Part 1:

The number of people with morbide obesitas in the Western World has increased a
lot the past 10 years. During this period the number of bariatric procedures in
the Netherlands increased from a 1000 interventions in the year 2000 to 9000
interventions in 2012. Bariatric procedures can be divided in restrictive
techniques, malabsorptieve techniques or a combination of both. The Adjustable
Gastric Band (AGB) an the Gastric Sleeve (GS) are restrictive techniques, the
Roux-en-Y gastric bypass (RYGB) is a combined technique with a average weight
loss of 60-70 %. Unfortunately vitamin and mineral deficiency is a consistent
effect of the malabsorptie and reduced intake after the surgery. Iron
deficiency is known in 14-66% of the cases in the first two years after
surgery. A postoperative identified irondeficiency will be supplied with oral
ironsupplements. There are three preparations who are used worldwide. The most
common oral preparations are ferrous fumarate and Losferron (ferrogluconaat).
When deficiency doesn*t improve with oral supplements patients will be treated
with Ferinject (iron(III)carboxymaltose).
It is of importance to treat an irondeficiency to prevent a microcytic anemia
and fatigue caused by irondeficiency.
The risk of developing iron deficiency anemia after RYGB is the most high in
premenopausal women.

Part 2:

There are indications that the absorption of oral iron supplementation is
reduced after a RYGB. Nevertheless, oral preparations are used as standard
therapy for iron deficiency, even in patients who underwent a RYGB. To take a
better look at the absorption of iron after a gastric bypass, we'll perform an
ironabsorption test in the period pre- and postoperative. This part of the
study will be performed only in the Rijnsate Hospital in Arnhem.
Hypothesis: when the ironabsorption test shows major differences in absorption
after a RYGB, we may predict in the future the effectiviness of oral
ironsuppletion.

Part 1:

Prospective evaluation of serum ferritin levels after suppletion with ferrous
fumarate, Losferron or Ferinject in patients with iron deficiency after primary
RYGB. Which therapy is the most effective one to replace ironstorage?
We also analyse the interval between initiation of therapy and adequate
correction of iron deficiency.

Part 2:

Evaluate if ironabsorption is disturbed after a RYGB, which leads to a
insufficient treatment of oral ironsuppletion.
Analyse if failure of oral ironsuppletion is predictable at baseline (T=0) in
the absorption test.

Part 1:

A prospective radomised controlled trial will be performed with 240 patients
who underwent a primary RYGB and postoperatively develop a irondeficiency
(ferritin < 20 microgram/l). Women (group 1) and men (group 2) will be
seperated in 2 groups of 120 patients. Irondeficiency is identified during the
postoperative follow-up (standard follow-up moments in our centre: 6,12,24 and
36 months).
Group 1 and 2 will be randomised in 3 treatment groups: treatment with ferrous
fumarate, losferron (ferrogluconate) or ferinject.

- Group 1A: irondeficiency in this women will be corrected by ferrous fumarate
200mg 3 times daily.
- Group 1B: irondeficiency in this women will be corrected by losferron 695mg 2
times daily.
- Group 1C: irondeficiency in this women will be corrected by a single shot
Ferinject, dosage will be examined for each patient individually. The
intravenous injection will be performed in the cilinical day centre.
- Group 2A: irondeficiency in this men will be corrected by ferrous fumarate
200mg 3 times daily.
- Group 2B: irondeficiency in this men will be corrected by losferron 695mg 2
times daily.
- Group 2C: irondeficiency in this men will be corrected by a single shot
Ferinject, dosage will be examined for each patient individually. The
intravenous injection will be performed in the cilinical day centre.

The effect of different ironsuppletions on the serum ferritin will be evaluated
6 weeks after starting treatment. When ironlevels awill not be normalized,
treatment will be continued and follow-up will be performed 12, 26 and 52 weeks
after starting therapy, including blood samples for ferritin.
During the appointments a questionairre will be filled in to evaluate the route
of administration preference of the patient (oral suppletion vs. intravenous
injection).

Part 2:

Prospective monocentre study (only in the Rijnstate Hospital Arnhem).
Twenty-four patients will perform an ironabsorption test pre- and
postoperatively. There will be randomized between 2 groups ( each group
contains 12 patients).

Preoperatively: group 1 receives a daily dose of ferrous fumarate (600mg) and
group 2 receives a daily dose Losferron (1390mg).
Before intake of the medicins, a fasting bloodsample is taken (baseline), serum
iron including ferritin, transferrin and transferrin saturation will be
measured. After intake of losferron/ferrous fumarate blood samples will be
taken 1, 2, 3, 4, 5 and 6 hours after intake, using a drip. An increase of 80
microgram/l is representative for a sufficient ironabsorption.

Postoperatively; one month postoperatively the same absorption test will be
repeated in the same patients.

Part 1:

Participants who received oral iron supplementation in this study, will not
experience any direct benefit, because it is the standard treatment for
irondeficiency.
The study is designed to optimize the treatment for irondeficiency developed
after RYGB and to evaluate the most preferred suppletionmethod for the patient.
Patients who have an irondeficiency are treated with ferrous fumarate or
Losferron (group 1A, 1B and 2A and 2B).
Group 1C, and 2C are treated with Ferinject. These patients (group C) may have
the advantage that after one intravenous injection the serum ferritin
normalizes and no further treatment is needed, they do not need daily
administered oral iron suppletion. Patients in the Ferinject-group need to stay
a half day in the hospital. The possible disadvantages can be the side effects
of Ferinject (see adverse Ferinject, Chapter 9 in the protocol).

Part 2:

Participants in this study will not experience a direct benefit. The study was
set up to optimize iron suppletion in patienst who developed a irondeficiency
after RYGB. Irondeficiency is frequently seen after a RYGB. A ironabsorption
test will be performed. Participants receive in the periode before and after
the operation a single dose Losferron / ferrous fumarate. An infusion is
aplied. Blood will be collected from the applied infusion, in total 14 times: 7
times preoperatively and 7 times postoperatively