# Bowel Preparation for Colonoscopy with Sodium Phosphate Solution versus Polyethylene Glycol-Based Lavage: A Multicenter Trial

Authors: S. Schanz; W. Kruis; O. Mickisch; B. Küppers; P. Berg; B. Frick; G. Heiland; D. Hüppe; B. Schenck; H. Horstkotte; A. Winkler
Journal: Diagnostic and Therapeutic Endoscopy
 (2008)

---

## Abstract

Background: Adequate bowel preparation is essential for
accurate colonoscopy. Both oral sodium phosphate (NaP) and
polyethylene glycol-based lavage (PEG-ELS) are used predominantly
as bowel cleansing modalities. NaP has gained popularity due to
low drinking volume and lower costs. The purpose of this
randomized multicenter observer blinded study was  to compare
three groups of cleansing (NaP, NaP + sennosides, PEG-ELS +
sennosides) in reference to tolerability, acceptance, and
cleanliness. Patient and Methods: 355 outpatients between 18 and
75 years were randomized into three groups (A, B, C) receiving NaP =
A, NaP, and sennosides = B or PEG-ELS and sennosides = C.
Gastroenterologists performing colonoscopies were blinded to the
type of preparation. All patients documented tolerance and adverse
events. Vital signs, premedication, completeness, discomfort, and
complications were recorded. A quality score (0–4) of cleanliness
was generated. Results: The three groups were similar
with regard to age, sex, BMI, indication for colonoscopy, and
comorbidity. Drinking volumes (L) (A =  4.33 + 1.2, B =  4.56 + 1.18, C = 4.93 + 1.71) were in favor of NaP
(P = .005). Discomfort from
ingested fluid was recorded in  A = 39.8%  (versus C: P = .015),
B = 46.6%  (versus C: P = .147), and C =  54.6%.  Differences in tolerability and acceptance between the three groups were
statistically not significant. No differences in adverse events
and the cleanliness effects occurred in the three groups (P = .113).
The cleanliness quality scores 0–2 were calculated in A:
77.7%, B: 86.7%, and C: 85.2%. Conclusions:
These data fail to demonstrate significant differences in
tolerability, acceptance, and preparation quality between the
three types of bowel preparation for colonoscopy. Cleansing with
NaP was not superior to PEG-ELS.


---

## Body

## 1. Introduction

Colonoscopy is performed as a principal
diagnostic tool in most colonic disorders. Adequate bowel preparation is
essential for proper visualization of mucosa. Superior cleansing minimizes the
risks of missed lesions and repeated procedures, and decreases patients’
discomfort and costs of colonoscopy [1, 2].Peroral polyethylene glycol (PEG) solution has
been the cleansing agent most used in recent years. This nondigestible, nonabsorbable osmotically balanced laxative lavage solution does not alter
fluid and electrolyte balance  [3–6]. Despite the improved tolerance to the two-day standard preparation of clear
liquids, laxatives, and enemas, the large fluid intake may lead to nausea and abdominal discomfort.Sodium phosphate (NaP), a highly osmotic
laxative, has also proven to be an effective and well-tolerated agent  [7]. Because of the small quantity needed, it
has become one of the preferred agents. Over the past decade, numerous studies
have demonstrated that oral NaP is even better tolerated and results in more
effective colon cleansing compared with PEG [8–13].Despite its popularity, NaP generally fails to show better efficacy than
PEG-ELS.In some less comprehensive studies, PEG-ELS preparation even yields better
results [14–17].The purpose of this prospective randomized
observer-blinded multicenter study was to compare not only tolerability as
the primary aim,  but also the efficacy and safety profile of the
bowel preparation solely using NaP versus NaP and PEG in combination with
sennosides as an adjunctive laxative.


## 2. Patients and Methods

A total of 360 patients were recruited during
a four-month period, of which 355 consecutive outpatients aged between 18 and 75 years were
included in the study, undergoing colonoscopy in 5 endoscopy centres after
cleansing preparation. Indications for colonoscopy were history or symptoms of
intestinal complaints, weight loss, anaemia, or control of persistent diseases. Patients with an urgent indication for
colonoscopy, intolerance to one of the used components, or insufficient
compliance were excluded from the study. Patients were randomized into three
preparation protocols and analysed for tolerability, efficacy, and safety. They
were instructed to remain on a clear liquid diet for 24 hours prior to the
procedure. According to the type of the study using well-established routine
procedures, for legal reasons no formal ethical approval was necessary. The
study was conducted in line with the ethical commitments of the hospital. All
patients gave written informed consent. The study was sponsored by Ferring, Germany,
without any intellectual or substantial input into the study protocol and
analysis of results.


## 3. Bowel Preparation

### 3.1. NaP (Group A)

NaP (Fleet Phospho-soda, Ferring, Germany)
was administered in two doses of 45 mL each, containing 10.8 g disodium
phosphate dodecahydrate and 24.4 g sodium dihydrogen phosphate dihydrate.
According to the protocol, the first dose was given in the evening before the examination
(19:00 p.m.), and the
second in the morning before the procedure (7:00 a.m.). Each dose was diluted in 120 mL of cold
water followed by other 240 mL of cold water. The day before colonoscopy the
patient was encouraged to drink at least 3 L or more of clear liquids.


### 3.2. NaP + Sennosides (Group B)

In addition to Group A protocol, sennosides
preparation (X-Prep, Mundipharma, Germany) as a supplemental laxative was given
the day before the procedure (14:00 p.m.). One dose of 75 mL contains 150 mg of standardized
hydroxyanthracene-glycosides (sennoside B). Laxative effects start 5–8 hours after the
intake. In addition, the patients had to drink at least a glass (240 mL) of
cold water. The day before colonoscopy the patient was encouraged to drink at
least 3 L or more of clear liquids within the following 4 hours.


### 3.3. PEG-ELS and Sennosides (Group C)

Patients receiving PEG-ELS were instructed to
remain on clear liquids (3-4 L) after a
light meal at 13:00 p.m.
the day before the examination. One dose of sennosides (X-Prep) was
administered at 14:00 p.m.. Before 7:00 a.m. on
the day of the procedure the patients were to drink 4 sachets of PEG-ELS
(Klean-Prep) diluted in 1 L of water per dose, containing 68.96 g of PEG 3350
with potassium chloride, sodium chloride, sodium hydrogen carbonate, and sodium
sulphate. The intake of PEG-ELS (250 mL each within 10–15 minutes)
before colonoscopy was continued until cleanliness of faeces was proven or a
maximum volume of 4 L was consumed.Prior to the examination, patients rated their tolerability of the drinking volume, and the entire
preparation received a rating of good, moderate, or poor. Adverse events were
recorded according to GCP in detail in the case-report form and carefully monitored
by the trial investigator and the sponsor. They were also evaluated (none,
mild, moderate, and severe) by each patient. All recorded adverse events were specified and
listed in the final report.Demographic data, comorbidity, and medication
of the study population were also documented before allocation to the
corresponding preparation regimen according to the random list.Each colonoscopy was performed by an
experienced endoscopist blinded with regard to the preparation protocol. Commencement of the endoscopic
procedure was between 11:00 a.m. and 1:00 p.m. The acquisition of information about
bowel cleansing methods was not
permitted. Premedication, vital
signs, and complications during the procedure were documented including reasons
for incomplete endoscopy. Discomfort of the ingested fluids was qualified in a
verbal rating scale as “no, slight, moderate, or strong discomfort.” The
quality of cleanliness and visibility of the colonic mucosa were scored
according to a modified five-level rating scale used in prior clinical studies [7–9, 17, 18, 19] (see Table 1).Table 1
Cleanliness quality score of the blinded endoscopist.
0Dry colon, no solid faeces1Only transparent fluid2Fluid faeces3Small amount of solid faeces,≥90% of the mucosa visible4Solid faeces,<90% of the mucosa visible


### 3.4. Statistics

Statistical analysis was based on group
randomisation to enable allocation of each consecutive patient to the predetermined random list. Computer-generated
randomisation lists were applied to each participating centre. Each working day
was assigned to one treatment group, resulting in the same preparation protocol
for all patients studied at a particular day. Comparison of the three
preparation modalities A, B, and C was realized by analysis of variance (ANOVA),t-test, U-test, χ2 (chi-square) test
for testing each regimen pair, Kruskal-Wallis test (K-W test), Mantel-Haenszel X2 test for additional pair comparison (XMH2: test of linear
relation between columns of cross-tables),
analysis of factors, and test of equivalence for responder rates. All tests
were conducted two-sided. P<.05 was considered to demonstrate
statistical significance or equivalence, and respective numbers were given as
mean ± standard deviation. The primary objective was to demonstrate a 20% superior
tolerability of the treatment arm A. If significant, equivalent efficacy of NaP
+ sennosides (B) compared with PEG-ELS + sennosides (C) was tested (good and
excellent effects) on the basis of a level of equivalence of 15% and a success
rate of at least 85% of the standard which was defined hypothetically as
PEG-ELS + sennosides. If significant, equivalent efficacy of NaP (A) compared
with PEG-ELS + sennosides (C) was tested on the basis of a level of equivalence
of 15% and a success rate of at least 85% of the standard. Accordingly, group
sizes of at least 107 patients were calculated to test superiority with a power
of 1−β=0.80. For data management and statistical analyses, the SAS software
was used.


## 3.1. NaP (Group A)

NaP (Fleet Phospho-soda, Ferring, Germany)
was administered in two doses of 45 mL each, containing 10.8 g disodium
phosphate dodecahydrate and 24.4 g sodium dihydrogen phosphate dihydrate.
According to the protocol, the first dose was given in the evening before the examination
(19:00 p.m.), and the
second in the morning before the procedure (7:00 a.m.). Each dose was diluted in 120 mL of cold
water followed by other 240 mL of cold water. The day before colonoscopy the
patient was encouraged to drink at least 3 L or more of clear liquids.


## 3.2. NaP + Sennosides (Group B)

In addition to Group A protocol, sennosides
preparation (X-Prep, Mundipharma, Germany) as a supplemental laxative was given
the day before the procedure (14:00 p.m.). One dose of 75 mL contains 150 mg of standardized
hydroxyanthracene-glycosides (sennoside B). Laxative effects start 5–8 hours after the
intake. In addition, the patients had to drink at least a glass (240 mL) of
cold water. The day before colonoscopy the patient was encouraged to drink at
least 3 L or more of clear liquids within the following 4 hours.


## 3.3. PEG-ELS and Sennosides (Group C)

Patients receiving PEG-ELS were instructed to
remain on clear liquids (3-4 L) after a
light meal at 13:00 p.m.
the day before the examination. One dose of sennosides (X-Prep) was
administered at 14:00 p.m.. Before 7:00 a.m. on
the day of the procedure the patients were to drink 4 sachets of PEG-ELS
(Klean-Prep) diluted in 1 L of water per dose, containing 68.96 g of PEG 3350
with potassium chloride, sodium chloride, sodium hydrogen carbonate, and sodium
sulphate. The intake of PEG-ELS (250 mL each within 10–15 minutes)
before colonoscopy was continued until cleanliness of faeces was proven or a
maximum volume of 4 L was consumed.Prior to the examination, patients rated their tolerability of the drinking volume, and the entire
preparation received a rating of good, moderate, or poor. Adverse events were
recorded according to GCP in detail in the case-report form and carefully monitored
by the trial investigator and the sponsor. They were also evaluated (none,
mild, moderate, and severe) by each patient. All recorded adverse events were specified and
listed in the final report.Demographic data, comorbidity, and medication
of the study population were also documented before allocation to the
corresponding preparation regimen according to the random list.Each colonoscopy was performed by an
experienced endoscopist blinded with regard to the preparation protocol. Commencement of the endoscopic
procedure was between 11:00 a.m. and 1:00 p.m. The acquisition of information about
bowel cleansing methods was not
permitted. Premedication, vital
signs, and complications during the procedure were documented including reasons
for incomplete endoscopy. Discomfort of the ingested fluids was qualified in a
verbal rating scale as “no, slight, moderate, or strong discomfort.” The
quality of cleanliness and visibility of the colonic mucosa were scored
according to a modified five-level rating scale used in prior clinical studies [7–9, 17, 18, 19] (see Table 1).Table 1
Cleanliness quality score of the blinded endoscopist.
0Dry colon, no solid faeces1Only transparent fluid2Fluid faeces3Small amount of solid faeces,≥90% of the mucosa visible4Solid faeces,<90% of the mucosa visible


## 3.4. Statistics

Statistical analysis was based on group
randomisation to enable allocation of each consecutive patient to the predetermined random list. Computer-generated
randomisation lists were applied to each participating centre. Each working day
was assigned to one treatment group, resulting in the same preparation protocol
for all patients studied at a particular day. Comparison of the three
preparation modalities A, B, and C was realized by analysis of variance (ANOVA),t-test, U-test, χ2 (chi-square) test
for testing each regimen pair, Kruskal-Wallis test (K-W test), Mantel-Haenszel X2 test for additional pair comparison (XMH2: test of linear
relation between columns of cross-tables),
analysis of factors, and test of equivalence for responder rates. All tests
were conducted two-sided. P<.05 was considered to demonstrate
statistical significance or equivalence, and respective numbers were given as
mean ± standard deviation. The primary objective was to demonstrate a 20% superior
tolerability of the treatment arm A. If significant, equivalent efficacy of NaP
+ sennosides (B) compared with PEG-ELS + sennosides (C) was tested (good and
excellent effects) on the basis of a level of equivalence of 15% and a success
rate of at least 85% of the standard which was defined hypothetically as
PEG-ELS + sennosides. If significant, equivalent efficacy of NaP (A) compared
with PEG-ELS + sennosides (C) was tested on the basis of a level of equivalence
of 15% and a success rate of at least 85% of the standard. Accordingly, group
sizes of at least 107 patients were calculated to test superiority with a power
of 1−β=0.80. For data management and statistical analyses, the SAS software
was used.


## 4. Results

355 out of 360 patients between 17 and 82
years (median age of
59 years) participated in the
study with an indication for a complete colonoscopy. Comorbidity was present in
194 patients
(54.6%), mostly with cardiovascular diseases (23.1%) followed by diseases of
gastrointestinal tract (16.9%) and endocrine or metabolic abnormalities
(13.0%). Medication of concomitant diseases was documented in 174 patients (49%). Characteristics of the patients randomized
into the three groups (A, B, and C) are outlined in Table2.Table 2
Characteristics of the patients separated by
the cleansing protocol (A, B, and C).
ABCTotalNumber12813394355Age (median)615957.559BMI  (kg/m2)25.124.924.925Indication for colonoscopyAbdominal symptoms38.3%40.6%38.3%139 (39.2%)Other7.8%9.8%7.4%30 (8.5%)Suspected colonic disorder23.4%24.1%20.2%90 (25.4%)Control of colonic disease32%24.1%20.2%92 (25.9%)Aggravation of colonic disease5.5%8.3%8.5%26 (7.3%)Comorbidities57.8%49.6%57.4%194 (54.6%)The three groups were similar with regard to
age, BMI, indication for colonoscopy, and comorbidities. Compliance with the
cleansing protocol was also comparable between groups A (99.2%), B (97.7%), and
C (95.7%). All patients were examined in 5 centres. The distribution of
patients to each centre (C) was as follows: C1:n=73, C2: n=69, C3: n=36, C4: n=111, and C5: n=67. The reason for the disproportion of patients in the
groups A, B, and C was due to lower numbers of colonoscopies in centres 3 and 4
on the examination days randomized to C.The total volume of administered fluids for
bowel cleansing in the three groups varied (A: 4.33 L, B: 4.56 L, and C: 4.93 L;
ANOVA:P=.005, Kruskal-Wallis: P=.015). Discomfort according to
the verbal rating scale showed a significant difference between Group A and Group
C in pair analysis (see Figure 1).Figure 1
Percentages of
patients with (slight to strong) or without discomfort of ingested liquids (X2test: P=.015).All relevant symptoms during preparation were
protocolled (nausea, vomiting, abdominal pain or bloating, anal irritation,
fatigue, sleep disorder, hunger, weakness, chest pain, chills). Factor analysis
showed heterogeneity between the three groups without relevant differences (see
Figure2). Subgroup analyses showed a higher proportion of patients (>70
years) with nausea and vomiting (nausea: 16 versus 9 patients of >70 years,
41 versus 67 patients of <70 years (K-W test: P =.004); vomiting: 9 versus
16 patients of >70 years, 14 versus 94 patients of <70 years (K-W test: P=.012)).Figure 2
Profile of symptoms during bowel preparation in the three groups (%).No significant difference in global
tolerability of each preparation regimen could be ascertained (see Figure3).Figure 3
Tolerability of
the three preparation modalities received a rating of good, moderate, or poor.Complete examination of the colon was possible
in 94.9% of the patients. Premedication, vital signs, and pain before and
during colonoscopy were registered and were similar in the three groups. The
assessment of the cleanliness quality was evaluable in 337 patients in which
complete colonoscopy could be achieved.
Cleansing efficacy was high in all three groups, and there was no
statistical difference. Group C (PEG-ELS + sennosides) tended towards a better
response in the analysis of details with regard to all scores (see  Figure4). The rates of good and very good cleanliness quality were 77.7% in Group A,
86.7% in Group B, and 85.2% in Group C (P=.135 in X2 test) (A
versus B: P=.062, A versus C: P=.171, B versus C: P=.755).Figure 4
Cleanliness
responses to bowel preparation as a percentage between the three groups.
Cleansing rating includes excellent and good(P=.013).Acceptance was high in all groups. Similar
proportions of patients were reported to refuse repetition of the same
preparation regimen: Group A = 14.8%, Group B = 18.5%, and Group C = 17% (X2 test: P=.737).  If there is
alternative preparation offered for colonoscopy, patients would prefer another
protocol in A: 30.2%, B: 30%, and C: 37.2% (X2 test: P=.445).


## 5. Discussion

Colonoscopy is an important tool for the
diagnosis and follow-up of colonic disorders and the prevention of neoplasms.
There is an ongoing search for the ideal cleansing preparation, aiming at
better patient compliance, shorter colonic preparation time, and better
cleansing effects. Consumption of a large amount of fluid is frequently
associated with poor patient tolerance. It might therefore be expected that a decrease in volume could lead to a
better acceptability.In the present study, bowel cleansing
preparation with NaP with or without sennosides was compared to a PEG
electrolyte solution with sodium sulphate (PEG-ELS) in combination with
sennosides in terms of tolerability, patient acceptance, and bowel cleanliness.
The investigation included a considerable number of patients. The differences
in the sizes of the three treatment arms are due to the randomisation procedure,
and may not very likely influence outcomes in the view of very similar baseline
characteristics.Our results of the present study indicate that
all three regimens showed a good tolerability with a trend towards PEG-ELS, but
this difference did not reach a level of statistical significance. As
demonstrated in other studies, NaP was not better tolerated although the
ingested volume of liquids was significantly lower (medium: 14%) in the NaP group.
Subgroup analysis in consideration of age however showed significantly more
side effects in patients over 70 years like nausea, vomiting, and abdominal
pain in Group B (NaP + sennosides). Dizziness and presyncope as symptoms caused
by volume depletion and hyperphosphatemia were not predominant in the NaP
regimens, which is concordant with the literature [20]. Vomiting and abdominal
discomfort reported as frequent side effects of PEG-ELS with a better tolerance
of NaP [21] were not increased in the PEG-ELS group.Acceptance of the three preparation protocols
was similar. Less than 20% of each group would not like to repeat the same
regimen for bowel cleansing. Also similar proportions of patients would prefer
another cleansing solution for the next colonoscopy with an insignificant trend
towards NaP protocols. Considerably better results in acceptance were reported
in literature when NaP was compared with PEG solutions [8–10, 21, 22, 23].Regarding the cleanliness effects, all three
preparation protocols were highly effective with a very good or good response
between 77.7% and 86.7%. Overall cleanliness of the colon was assessed without
specifying the cleansing effects in the different bowel segments. According to
a worst-case analysis, solid faeces in any of the segments was judged as
cleanliness score 4 and transparent fluid in all segments as good (score
1). In contrast, Ell et al. [27]
analysed the effects of bowel preparation of different segments, which gives some additional
information. Because of the high number of patients, we chose a less complex
protocol, also omitting systematic videotaping.Although there was a trend towards better
cleanliness with PEG-ELS plus sennosides, the differences showed no statistical
significance. Similar responses were reported by others [18, 22–26].It is widely established to perform bowel
cleansing with PEG-ELS within 2 consecutive days. Because of adding
sennosides to the preparation protocol taken the day before the examination,
there was no distribution of the amount of PEG-ELS on two days with an
overnight pause. Hence, in our protocol the whole PEG-ELS dose was taken over
at least 4–6 hours on the
day of the examination under strict control of the unblinded endoscopy
assistant nurses of each centre. Then colonoscopy was commenced.In a recent study by Ell et al. [27], the PEG-ELS (with sodium sulphate) treatment group demonstrated
the optimal cleansing quality in all colon segments compared to PEG-ELS
(without sodium sulphate) and NaP. No details were given on the amount of
liquids taken together with each preparation regimen, which in our opinion
plays an important role in the NaP cleansing. Furthermore, most of the examined subjects were
inpatients (86%)—a treatment group
with generally more severe illnesses or at least more severe comorbidity which
may affect bowel preparation. Therefore,
it cannot be compared with our treatment group made up exclusively of
outpatients. PEG-ELS doses
were administered in two portions on the day before and the day of the
examination, which might be an advantage referring to cleanliness of proximal
colonic segments [19].Despite the administration in a two-step
procedure with an overnight pause, NaP showed no better results than PEG-ELS
plus sennosides as in the study of Frommer [10]. Colonoscopy was performed at
the earliest 3-4 hours after the
second dose of NaP.The combination of NaP with sennosides, a
commonly used laxative to optimize bowel preparation for diagnostic procedures [28],
produces a slightly better cleanliness response than NaP alone. But this minor
synergistic effect does not reach statistical significance. On the other hand,
there was a tendency towards
more side effects, as mentioned above.A meta-analysis of the trials comparing NaP
with PEG solutions concluded that oral NaP was better tolerated by patients and
was at least as efficacious [29].But heterogeneous groups of patients,
outpatients, and inpatients and different protocols were mixed up, which limits
the conclusion.Each preparation protocol was carried out
according to the dosing instructions recommended for afternoon colonoscopies. Being
consistent with the recommendation of the ASGE, patients with severe renal
insufficiency or unstable cardiac diseases were excluded from the study [30].


## 5. Conclusion

In conclusion, tolerability, acceptance, and
the effectiveness of the bowel cleansing regimens for elective colonoscopy with
two-dose, low-volume NaP and 4 L PEG-ELS plus sennosides were comparable.
Sennosides as adjunctive laxative have only minor synergistic effects when added to NaP, and cannot be
recommended for routine endoscopy.There are still conflicting data regarding the
optimal bowel preparation for colonoscopy. This study was carried out to
compare the tolerability, safety, and efficacy of three (two) widely used bowel
lavage solutions in a large cohort of outpatients. Tolerability and safety were
evaluated by means of a symptom questionnaire completed by each patient before
the procedure. The scoring of cleanliness was performed during each examination
by the blinded endoscopist. The treatment groups were comparable with regard to
the baseline characteristics.



---

*Source: 713521-2008-07-14.xml*