Received: 10 August 2021

| Revised: 19 November 2021

| Accepted: 28 November 2021

DOI: 10.1111/ipd.12945

ORIGINAL ARTICLE

Efficacy of an iodoform-­based filling material for

pulpectomy of primary teeth: A 24-­month non-­inferiority
randomized clinical trial

Carmela R. Bresolin1,2 | Renata P. S. Marques1 | Bruna Okamura1 |

Claudio Costa3 | Cacio Moura-­Netto4 | Juan S. Lara5 |
Anna Carolina V. Mello-­Moura | Fausto M. Mendes
4 1

1
Department of Pediatric Dentistry,
School of Dentistry, University of São Abstract
Paulo, São Paulo, Brazil Aim: The aim of this non-­inferiority randomized clinical trial was to compare
2
Faculdades Metropolitanas Unidas, the efficacy of an iodoform-­based paste (Guedes-­Pinto –­(GP)) as a filling material
School of Dentistry, São Paulo, SP,
Brazil
in pulpectomies of primary teeth, and a standard material composed by calcium
3
Department of Stomatology, School of hydroxide and iodoform (CaOH/Iodof paste; Vitapex®).
Dentistry, University of São Paulo, São Design: A total of 104 teeth from 61 children (3–­8 years old) were randomly al-
Paulo, Brazil
located to two groups according to filling materials. Children were followed up
4
Faculty Dental Medicine, Center for
for 24 months. The primary endpoint was the treatment success rate evaluated
Interdisciplinary Research in Health—­
SalivaTec Lab, Universidade Católica through clinical and radiographic examinations at follow-­up, and the secondary
Portuguesa, Viseu, Portugal outcome was the analysis of the canal filling quality. Differences in the propor-
5
Department of Cariology, Operative tion of treatment success was calculated based on 95% confidence intervals (95%
Dentistry and Dental Public Health,
Indiana University School of Dentistry, CI) and with the Miettinen and Nurminen method in the intention-­to-­treat popu-
Indianapolis, Indiana, USA lation, considering a −20% of the non-­inferiority limit.
Results: From 104 randomized teeth, 102 were followed up after 24 months (at-
Correspondence
Fausto M. Mendes, Faculdade de trition rate of 1.9%). The success rate of teeth treated with the GP paste was 86.8%
Odontologia da Universidade de São (95% CI: 69.9–­94.9) and 78.4% (95% CI: 61.8–­89.1) with the CaOH/Iodof paste.
Paulo, Av. Lineu Prestes, 2227, São
Consequently, a non-­inferiority of the GP paste was observed when compared to
Paulo, SP, Brazil, Zip Code: 05508-­000.
Email: fmmendes@usp.br the CaOH/Iodof paste (P < .001).
Conclusion: The GP paste has a non-­inferior success rate than the CaOH/Iodof
Funding information
Coordenação de Aperfeiçoamento de
paste used as filling material for pulpectomy in primary teeth.
Pessoal de Nível Superior
KEYWORDS
endodontic treatment, iodoform-­based pastes, primary teeth, pulpectomy, randomized clinical
trials

1 | I N T RO DU CT ION necrosis, endodontic treatment is one treatment option to

Dental caries in primary teeth is the most prevalent
chronic disease affecting children1 and negatively impacts
children's quality of life.2 When more severe stages of car-
ies lesions reach the pulp-­dentin complex, leading to pulp
maintain primary teeth until exfoliation.2–­5
Most techniques for nonvital pulp therapy of primary
teeth involve root canal instrumentation and filling with
resorbable materials. Zinc oxide eugenol (ZOE)-­ based
paste and calcium hydroxide and iodoform paste4–­6 are the

668 | © 2021 BSPD, IAPD and John Wiley & Sons Ltd wileyonlinelibrary.com/journal/ipd Int J Paediatr Dent. 2022;32:668–677.
BRESOLIN et al
most commonly used canal filling materials. No consensus
on the most efficacious, however, has been reached, and
main conclusions come from low-­to moderate-­quality ev-
idence. Therefore, additional well-­designed clinical trials
are necessary.
Calcium hydroxide/iodoform (CaOH/Iodof) paste
(Vitapex®; Neo-­ Dental Chemical Products Co. Ltd.,
Tokyo, Japan) is one options for root canal filling after
a pulpectomy procedure in primary teeth. Developed in
the early 1980s in Japan,7 it is composed of 30.0% cal-
cium hydroxide, 40.4% iodoform, 22.4% silicone oil and
6.9% inert material. The resulting material is stored in
syringes and easily delivered into the root canal with
disposable tips provided by the manufacturer. The suc-
cess rate of the CaOH/Iodof paste for pulpectomies in
primary teeth has been assessed in several clinical trials
with acceptable results.4,5 The effectiveness of CaOH/
Iodof paste, as well as its ease of use and delivery sys-
tem, make it the material of choice for pulpectomies in
primary teeth.
Despite the abovementioned advantages of Vitapex®,
it is not commercially available in many countries, in-
cluding Brazil.8 Thus, Brazilian clinicians have frequently
had to use alternative filling materials for pulpectomies
in primary teeth. Until 2010, the most common mate-
rial in Brazil was an iodoform-­based paste, known as the
Guedes-­Pinto (GP) paste.9 This paste was proposed in the
early 1980s, with its first manuscript published in 1981
in Portuguese.10 Since then, several preclinical studies
focused on cytotoxicity, histopathological and microbio-
logical effects, and some non-­randomized clinical studies
have been conducted. A comprehensive review of these
studies has been previously published.11
The GP paste is composed of iodoform, camphorated
paramonochlorophenol (PMCC) and a dermatological
ointment containing prednisolone acetate and ryfami-
cin10,11 with the proportion of 69.2%, 7.0% and 23.8% re-
spectively.12 Despite its common use as filling material
for nonvital therapy in primary teeth in Brazil, no well-­
designed clinical trials have yet been conducted. If it were
possible to demonstrate at least the non-­inferiority of the
GP paste against the widely used CaOH/Iodof paste, the
GP paste could be a feasible alternative in countries where
the CaOH/Iodof paste is not available.
Therefore, this non-­ inferiority randomized clinical
trial was conducted to test the efficacy of the GP iodo-
form paste as a filling material in pulpectomies of primary
teeth compared with the CaOH/Iodof paste, commercially
available as Vitapex®. Our working hypothesis is that end-
odontically treated primary teeth filled with the GP paste
have a non-­inferior success rate than those filled with the
CaOH/Iodof paste.
   | 669
Why this paper is important to paediatric
dentists
• Endodontic treatment of primary teeth with
root canal instrumentation and filling with ab-
sorbable iodoform-­based materials reaches suc-
cess rates higher than 70%.
• Iodoform paste filling material used in Brazil
presents a non-­inferior success rate than the
commercially available calcium hydroxide/io-
doform paste (Vitapex®).
• The quality of root canal filling with both mate-
rials is similar with both material fillings.
2 | MATERIALS AND METHO D S
2.1 | Trial design and ethical
considerations
This is a randomized non-­inferiority clinical trial with
two parallel arms with a 1:1 allocation rate and two years
of follow-­up. The manuscript was written following the
Consolidated Standards of Reporting Trials (CONSORT)
statement and its extension for non-­inferiority and equiv-
alence trials.
The study protocol was approved by the Research
Ethics Committee of the School of Dentistry, University
of São Paulo (Certificate of Presentation for Ethical
Consideration 31034514.1.0000.0075) and registered on
ClinicalTrials.gov (NCT02216942) on 15 August 2014.
2.2 | Participants
Children aged 3–­8 years, whose parents sought dental
treatment for their child at the dental school and whose
child had at least one primary tooth with suspicion of ir-
reversible pulp involvement, were eligible to participate.
Children were assessed for eligibility only after both child
and guardian approved. The guardian signed a consent
form and the child provided verbal assent. Children with
any systemic or neurological disorder were excluded.
Moreover, patients with negative behaviour at the screen-
ing appointment were also excluded.
Potentially eligible teeth were clinically examined, and
then, periapical radiographs were taken using Kodak in-
sight radiographic films of 22 × 35 mm or 30 × 40 mm
(Eastman Kodak, Rochester, USA), with an X-­ray machine
(Dabi Atlante, Ribeirão Preto, Brazil) set to 70-­kV, 8-­mA
and 0.3-­s time exposure. This radiograph was used to aid
670 |    BRESOLIN et al
different steps of the subsequent treatment once the tooth
was included. Film holders (Jon Han-­Shin, Jon Ind., São
Paulo, Brazil) were used whenever the child allowed.
Included teeth were present with clinical or radio-
graphic signs of irreversible pulpal involvement such as
the presence of fistula, abscess, clinical pulp exposure due
to caries lesions, radiographic presence of endodontic le-
sions or pathological root resorption. We excluded teeth
with more than two-­thirds root resorption, advanced in-
ternal or external resorption, involvement of the perma-
nent successor bone follicle, or teeth with major coronal
destruction. If a participant presented with more than one
eligible tooth, all were included.
All treatments and assessments were conducted at
a dental office setting in the clinics of the School of
Dentistry, University of São Paulo, São Paulo, Brazil.
2.3 | Interventions
Each included tooth served as the randomization and
analysis unit. Teeth were randomly allocated to two differ-
ent groups of treatment based on the filling material: (1)
the CaOH/Iodof paste commercially available as Vitapex®
(reference treatment) and (2) the iodoform-­based Guedes-­
Pinto paste (experimental treatment).
All treatments were conducted following the same pro-
tocol, except for the root canal filling. A paediatric dentist
with additional specialty training in endodontics (CRB)
performed all endodontic treatments. Children were
treated after local anaesthesia, under rubber dam isola-
tion in a single session. Working length was determined at
1mm short of the apex on the initial radiograph. Carious
tissue was removed with hand excavators and spherical
drills, and pulp chambers was accessed with spherical dia-
mond burs initially, followed by noncutting tip burs (Endo
Z, Dentsply Maillefer, York, USA).
Manual instrumentation was performed using at least 3
sequential sizes of stainless steel Kerr-­type files (Dentsply
Maillefer, NY, USA). Irrigation during instrumentation
was done using 1% sodium hypochlorite solution (Asfer
Indústria Química, São Caetano do Sul, Brazil), finalizing
with 17% ethylenediaminetetraacetic acid (EDTA) irriga-
tion (Fórmula e Ação, São Paulo, Brazil). Consequently,
root canals were dried with capillary tips (Ultradent do
Brasil, Indaiatuba, Brazil) and absorbent paper points
(Dentsply Maillefer, NY, USA).
Allocated groups were disclosed at this time, and the
root canal was filled with one of the fillings materials:
(1) reference material—­the CaOH/Iodof paste: teeth al-
located to this group had their root canals filled with
Vitapex® (Neo-­Dental Chemical Products Co. Ltd., Tokyo,
Japan). The material was inserted into the root canals
using syringes and disposable tips provided by the manu-
facturer. The study protocol was blinded to the researcher
by covering all syringes with an opaque adhesive tape. (2)
Experimental material—­iodoform-­based GP paste: teeth
allocated to this group were filled with the GP paste.10,11
The GP paste is usually prepared manually at the time
of treatment,10 but for this study, syringes were purchased
from a dental product company (Angelus, Londrina,
Brazil), and the GP paste was stored in the same way as
the reference material and the syringe was covered with
an opaque adhesive tape. Disposable tips were used to in-
sert the material into the root canals.
A layer of Gutta-­Percha paste was applied on the pulp
chamber after filling to protect the treated root canals. All
teeth were restored using a resin-­modified glass ionomer
cement (Vitremer; 3M/ESPE, Minnesota, USA). The rub-
ber dam was removed and a final periapical radiograph
was taken, following the same parameters of the initial
radiograph. Regardless of the radiographically perceived
quality of filling, teeth were not endodontically retreated.
Children and guardians were instructed to return after
one week to assess adverse effects. Follow-­up visits took
place after 3, 6, 12, 16 and 24 months of the interventions.
Treated teeth were clinically evaluated at the 3-­, 6-­and 18-­
month follow-­up visits. Radiographs were only taken after
detecting any clinical sign of treatment failure. All treated
teeth received both clinical and radiographic examina-
tions at the 12-­and 24-­month visits.
Teeth with treatment failure were extracted and space
maintainers were placed, when indicated. Additionally,
all participants received full dental treatment besides end-
odontic treatments in the dental school clinic.
2.4 | Outcomes
The primary outcome was defined as the success of the
endodontic treatment after 24 months. Possible failures
were assessed at all recalls by an independent and blinded
outcome assessor, who did not participate in the dental
treatment sessions (RPSM). Clinical signs to define treat-
ment failures included the following: reported pain on the
treated tooth, pathological mobility and the presence of
fistula or abscesses. Failures were assessed by comparing
baseline and follow-­up radiographs. Failure was noted
when there was an increase in bone rarefaction in the
periapical (anterior) or furcal region (posterior) on treated
teeth. Abnormal resorption and rupture of the follicle
bone involving the permanent successor were also consid-
ered as signs of endodontic treatment failure. Total loss
of the restorative material was also classified as failure,
since contamination of the root canals would be possible.
Treatment success was a dichotomous variable assess on
BRESOLIN et al
each treated tooth, defined by the absence of all failure
signs as all follow-­up visits. A success rate was then calcu-
lated for both groups.
The percentage of root canal space filled in both groups
was assessed as a secondary outcome by measuring the
total area of the root canal observed in the initial radio-
graph and the filled area in the after-­treatment radio-
graph. The ratio of both measurements was calculated
per sample. All measurements were conducted digitally
on specific software (ImageJ, National Institute of Health,
USA) and were considered a quantitative variable (% of
root canal filled). Additionally, a categorical variable was
created by classifying teeth with more than 80%, and 80%
or less of root canal space filled.
The hypothesis of non-­inferiority was considered only
for the primary outcome. Both outcomes were originally
described in the clinical trial register, and no changes oc-
curred after the trial.
2.5 | Sample size
A minimum sample size, based on an estimated success
rate of 89% for the CaOH/Iodof paste,13 a limit of non-­
inferiority of 20% with 80% power and one-­sided α of 0.05,
was calculated. Under these parameters and consider-
ing the same estimated success rate for the experimental
paste, a minimum sample size was 60 teeth. Accounting
for clustering, 40% was added further, with 20% compen-
sating possible dropouts. A minimum sample size of 102
teeth (51 teeth per group) was reached. For the estimation
of the non-­inferiority limit, considering the success rate of
around 90% obtained in a previous clinical trial,13 we con-
sidered that a success rate above 70% would be acceptable.
2.6 | Randomization
The tooth was the unit of randomization with a 1:1 alloca-
tion ratio. The random allocated sequence was generated
on the www.seale​denve​lopes.com platform. Permuted
blocks (2, 4, 6 or 8 samples) were used in randomization
process, which was stratified by the type of teeth (anterior
or posterior primary teeth).
This sequence was generated for each stratum by a re-
searcher who was blinded to clinical procedures (FMM),
and was enclosed in individual and sequentially num-
bered opaque envelopes. If more than one tooth per child
was included, the order of the treatments was random. For
this, treatment teeth were ordered in an ascending man-
ner according to the Universal Tooth Numbering System,
and specific randomization lists were created for those
children using the sealedenvelopes.com platform. The
   | 671
operator conducted all endodontic treatments, and the
allocated group was disclosed only when the tooth was
prepared to be filled.
An external clinician (BO) assisted the operator and
was responsible for disclosing and allocating participants
to trial groups.
2.7 | Blinding
This is a triple-­blind study since all patients, operator and
outcome examiner were unaware of the allocated groups.
This was achieved through covering identical filling ma-
terial syringes with an opaque adhesive tape. Moreover,
both filling materials were yellow and presented similar
radiopacity due to the presence of iodoform in their com-
position. Hence, the only difference between groups was
a code—­syringe group A or B. The coding was placed in a
sealed opaque envelope during the study, and it was only
opened by the principal investigator (FMM) after the end
of follow-­ups, prior to the statistical analysis.
2.8 | Statistical methods
All analyses were performed based on intention-­to-­treat
(ITT), and the 95% confidence intervals (95% CI) were
adjusted for clustering. Conditional multiple imputation
(adjusted by trial groups and the presence of endodontic
lesion at the baseline) was employed to deal with missing
data (median of 15 imputations). The analyses considered
the included tooth as statistical unit for both primary and
secondary outcomes, and no person-­level analysis was
conducted.
To test the non-­inferiority hypothesis for the primary
outcome, the main analyses were based on 95% CIs ad-
justed for clustering. Therefore, non-­inferiority was de-
clared if the lower limits of the calculated 95% CI were
higher than −20%, considering the absolute differences be-
tween the success rate obtained with the treatment made
with the GP paste and the CaOH/Iodof paste filling mate-
rial. To support the interpretation based on the 95% CIs,
p values (non-­adjusted by the cluster) were derived using
Miettinen and Nurminen's score. In this statistical ap-
proach, the null hypothesis tested is that the experimental
treatment is inferior to the control treatment considering
a predetermined limit (non-­inferiority limit). Therefore,
obtaining p values lower than 5% indicated that the exper-
imental group is non-­inferior to the standard treatment.14
Sensitivity analyses were conducted considering the
proportion of successful cases, calculating the relative risk
(RR) and respective 95% CI adjusted for clustering. In this
case, non-­inferiority would be declared if the inferior limit
672 |    BRESOLIN et al
of the CI was higher than 0.80 and if the p value derived
by Miettinen and Nurminen's method was lower than 5%.
Additionally, a survival analysis using a two-­sample non-­
inferiority test using Cox regression was conducted, and
Kaplan-­Meier curves with 95% CI bands were plotted.
Subgroup analysis including only primary molars was
conducted for the primary outcome comparing groups by
using the difference in the success rate and proportion of
success, considering the same parameters previously de-
scribed to determine non-­inferiority.
The secondary outcome was analysed by comparing
both groups using two-­sided tests (P < .05) for the percent-
age of material filling the root canals. For this, linear and
Poisson regressions with robust variance were conducted
for the quantitative and dichotomous variables respec-
tively. The imputation procedures and regression analy-
ses were performed using Stata 15.0 (Stata Corp., College
Station, USA), and the non-­inferiority tests were carried
out using NCSS 2021 (NCSS LLC, Kaysville, USA).
3 | R E S U LTS
One hundred and four primary teeth in 61 children from
3 to 7 years of age were included and randomized (51 in
the CaOH/Iodof group and 53 in the GP group). Thirty
children (49.2%) were female and 31 (50.8%) were male,
and the mean age (SD) was 5.3 (1.2) years. Most chil-
dren (n = 36) had only one tooth included in the study.
Eighteen children participated with the inclusion of two
teeth, four children had three teeth included, two children
had five teeth included, and the other two children had
four and six teeth included, respectively.
A positive response rate of 98.1% was observed since
the 24-­month follow-­up was not achieved in only two chil-
dren (one tooth each). Both were allocated to the GP paste
group, and the dropout reason was family relocation.
Some children were not assessed at intermediate recalls,
but returned in subsequent follow-­up visits. Children were
included and treated from January 2015 to July 2015, and
were followed up until June 2017. Details are provided in
the study flowchart (Figure 1).
Table 1 displays baseline characteristics of the study
participants. A higher number of posterior teeth were
included. Furthermore, a higher proportion of nonvital
teeth was included (Table 1).
A higher frequency of treatment success was found
for teeth allocated to the experimental group (about 87%).
This frequency was, however, similar to the reference
material group (about 78%). The absolute difference be-
tween groups was 8.4%, with the lower limit of the 95%
CI reaching −6.5%, making it possible to declare that
the test material is non-­inferior (Table 2). Furthermore,
p value calculated by Miettinen and Nurminen's method
was lower than 0.05, rejecting the null hypothesis where
the experimental group would not be non-­inferior to the
reference material.
The same findings were observed in sensitivity analy-
sis when considering the RR between the two treatments
(Table 2). The lower limit of the 95% CI of the RR was
higher than 0.80, and the p value was lower than 5%. On
the contrary, non-­inferiority was not observed for other
sensitivity analysis using Cox regression. Considering the
failures and time of occurrence, the hazard ratio (95% CI)
was 0.61 (0.19 to 1.89), with a p value for non-­inferiority of
0.076. The Kaplan-­Meier curves are presented in Figure 2.
No endodontically treated anterior teeth failed after
24 months. Therefore, the subgroup analysis included
only primary molars, which confirmed non-­inferiority,
with the lower 95% CI limit for the success differences be-
tween treatments of −6.2%, and the lower 95% CI limit of
the RR of 0.92 (Table 2). The quality of root canal filling
showed no differences between groups in any of the quan-
titative or dichotomous variables (Table 2).
The main reason for treatment failure was the com-
plete loss of restorations (44.4% of all failures). Other
failures were due to clinical (33.3%) or radiographic signs
(22.2%). It was not possible to evaluate whether there were
differences in failure patterns between groups (Table 3).
No adverse events (e.g., allergic reactions, post-­
operative oedema, intense pain) were observed or re-
ported. Mild discomfort was referred by some children
few days after treatments, possibly due to the effect of
clamps on the gingiva during rubber dam isolation. The
latter occurred similarly in both groups.
4 | DISC USSION
Given the absence of commercial endodontic filling mate-
rials locally, and the wide use of iodoform-­based pastes for
pulpectomies in primary teeth in Brazil over 40 years,9,11
this trial was designed in an attempt to establish the ef-
ficacy of an iodoform-­based Brazilian paste in compari-
son with a reference material of choice available in many
countries, Vitapex® (CaOH/Iodof). It was hypothesized
that the experimental material would not be inferior to the
reference material, and therefore, a non-­inferiority design
was chosen to test such a statement. The main finding of
the present is that GP paste is non-­inferior to CaOH/Iodof
paste, in terms of success rate.
After 24 months, success rates obtained with both ma-
terials were higher than 75%, showing that the technique
of pulpectomy for primary teeth with the tested material
fillings is efficacious. The pulpectomy success rate with the
CaOH/Iodof paste obtained in this study is similar to that
BRESOLIN et al
FIGURE 1 Consort flow chart
obtained in a previous study with 6 months of follow-­up.13
Data from two recently published systematic reviews ar-
rive at similar conclusions. Based on the two included
studies, the authors of a systematic review observed that
the success rate of the CaOH/Iodof paste was 66% after
18 months.4 In another systematic review, the frequency
of success rate of the CaOH/Iodof paste evaluated from 4
studies after 12 months was 92% and 78% based on clini-
cal and radiographic evaluations respectively.5 The overall
success rate after 12 months was 84%, but this was based
only on two studies.5
The efficacy of the GP paste was similar to the efficacy
of the CaOH/Iodof paste. Studies using ZOE as root canal
   | 673
filling material have reported a slightly higher success rate,
varying from 87% to 98%.4,5 Such studies suggested that
ZOE pastes are better than the CaOH/Iodof -­based ones
after 125 and 18 months,4 however, based on low-­quality
evidence.4,5 Another systematic review reported success
rates varying from 85% to 100% for ZOE, and from 89%
to 100% for the CaOH/Iodof-­based pastes, with no signif-
icant differences between treatments.15 In relation to the
GP paste, no previous clinical trials have been conducted,
and therefore, comparisons were not possible.
The evidence for different techniques and materials for
pulpectomy procedures in primary teeth is weak. The vast
majority of the studies on pulpectomy in primary teeth
674 |    BRESOLIN et al

T A B L E 1 Baseline characteristics of the participants and

of non-­inferiority was established. Other methodological
included teeth by intervention group
strengths of the present study are its triple-­blinded nature
CaOH/Iodof paste GP paste and the achievement of a very low attrition rate (<2%).
Characteristics N (%) N (%) The success rate of the GP paste was superior to the ref-
Variable related to children (104 teeth in 61 children) erence treatment. The sensitivity analysis calculating the
Sex relative risk for the success of both treatments confirmed
Female 25 (51.0) 24 (49.0) the results obtained with the analysis of the primary end-
point. We did not, however, observe non-­inferiority with
Male 26 (47.3) 29 (52.7)
the survival analysis, although the upper limit of the CI
Age groups
was only slightly higher (1.33) than the HR considered to
Younger than 5 years old 14 (41.2) 20 (58.8)
show the non-­inferiority (1.20). One potential explanation
5 years or older 37 (52.9) 33 (47.1) is that the curves showed that success rates in both tech-
Variables related to teeth (104 teeth) niques were similar after 12 months. Subsequently, the
Tooth position failure rate in the teeth allocated to the CaOH/Iodof group
Anterior 10 (55.6) 8 (44.4) was higher than in the experimental group.
Posterior 41 (47.7) 45 (52.3) Interestingly, all anterior teeth treatments were suc-
Initial diagnosis cessful after 24 months. These teeth do not typically rep-
resent a significant technical challenge for clinicians.
Vital 15 (46.9) 17 (53.1)
Moreover, one of the main reasons for pulp damage in this
Nonvital 36 (50.0) 36 (50.0)
group of teeth is the occurrence of traumatic dental inju-
Abscess
ries instead of pulp necrosis related to dental caries. This
No 42 (50.0) 42 (50.0) may explain the good prognosis of endodontically treated
Yes 9 (45.0) 11 (55.0) anterior teeth. Thus, primary molars were analysed sepa-
Periapical lesion rately, and a significant non-­inferior performance of the
No 18 (43.9) 23 (56.1) GP paste in the subgroup analysis was also observed.
Yes 33 (52.4) 30 (47.6) A common reason for failures was restoration loss.
Root resorption Although this type of failure is not directly related to
the endodontic treatment, total restoration loss can lead
No 41 (50.0) 41 (50.0)
to root canal contamination. In the present study, all in-
Yes 10 (45.5) 12 (54.5)
cluded teeth were restored with resin-­modified glass ion-
Total 51 53
omer cement. A recently published study showed similar
Note: There were 2 dropouts, both at the experimental group. success rates in primary teeth endodontically treated with
CaOH/Iodof, calcium hydroxide and iodoform paste (reference filling the GP paste, but restored with bulk-­fill composite resin
material).
and stainless steel crowns. No differences were observed
GP, Guedes-­Pinto paste (experimental filling material).
between restorative materials.17 Therefore, there is no
conclusive evidence on which material is best to restore
have unclear or high risk of bias. Trials were conducted endodontically treated primary teeth, highlighting the
with small samples and in relatively short follow-­up time. need for further studies.
Only one study comparing ZOE and CaOH/Iodof mate- Our findings on the efficacy of the GP paste is not
rials included more than 100 teeth that were followed up surprising. Preclinical experiments have shown that the
for 18 months.16 Unfortunately, this latter study presented material has an acceptable cytotoxicity and that it is well-­
unclear risk of bias in several domains, such as random- tolerated by subcutaneous tissues in experiments with
ization and concealment procedures.5 animals. Furthermore, this material presents with antimi-
The present study had an adequate sample size consid- crobial activity against microorganisms usually found in
ering a non-­inferiority limit of 20% and a longer follow-­up infected root canals. In addition, some non-­randomized
interval (24 months). This non-­inferiority margin was esti- clinical trials have been conducted with acceptable success
mated based on a previous clinical trial that reached a suc- rates.11 Finally, and as stated before, the GP paste has been
cess rate of 90%13; therefore, it was estimated that a success used for about 40 years in many dental schools in Brazil,9
rate of 70% would be acceptable. In fact, a recently pub- with positive clinical experiences. This was, in part, the
lished systematic review presented an overall success rate reason why a randomized clinical trial was proposed.
of about 70% with the CaOH/Iodof paste4; hence, our esti- Traditionally, the GP paste is made by clinicians (or
mation was appropriate. Furthermore, the tested material dental assistants) at the time of treatment, adding and
would have reached a non-­inferiority even if a 10% limit mixing each component on a glass slab.10,11 The paste is
BRESOLIN et al    | 675

T A B L E 2 Success of endodontic
CaOH/Iodof paste GP paste p
treatment in the intention-­to-­treat
population compared by the groups and Primary outcome—­Treatment success
additional analyses N success/N total 40/51 46/53
a
% success (95% CI) 78.4 (61.8 to 89.1) 86.8 (69.9 to 94.9)
Absolute difference Reference 8.4 (−6.5 to 23.5) <.001b
(95% CI)a
Relative risk (95% CI)a Reference 1.11 (0.89 to 1.37) .001b
Subgroup analysis—­primary molars
N success/N total 30/41 38/45
a
% success (95% CI) 73.2 (54.5 to 86.1) 84.4 (65.2 to 94.0)
Absolute difference (95% Reference 11.3 (−6.2 to 28.9) .003b
CI)a
Relative risk (95% CI)a Reference 1.15 (0.88 to 1.50) .002 b
Secondary outcome—­quality of root canal filling
% of root canal filling
Quantitative variable 90.2 (86.1 to 94.4) 86.7 (82.4 to 91.0) .226c
Mean (95% CI)a
Dichotomous variable
N (%)
Higher than 80% 41 (80.4) 40 (75.5) .592d
80% or less 10 (19.6) 13 (24.5)
Note: CaOH/Iodof, calcium hydroxide and iodoform paste (reference filling material)
GP, Guedes-­Pinto paste (experimental filling material).
a
95% confidence intervals (95% CI) were adjusted by the cluster.
b
p Values were derived using Miettinen and Nurminen's method.
c
Two-­sided p value was derived by linear regression.
d
Two-­sided p value was derived by the Poisson regression with robust variance.

applied into the root canals with the aid of endodontic
files and/or lentulo spiral. One of the main difficulties in
this technique is the unclear right proportion of each com-
ponent. Hence, a previous study evaluated the proportion
of the different components based on the opinion of clini-
cians with different backgrounds, such as clinicians, spe-
cialists and graduate students.12
A patent request was submitted to the Brazilian Patent
and Trademark Office (INPI) in 2008, based on the pro-
portions found in the previous investigation,12 plus some
preservatives and antioxidants. A patent was granted in
2018 (register number PI 0802256-­9, INPI/Brazil). For the
present study, a Brazilian dental material company pro-
duced a GP paste prototype and was stored in syringes
similar to CaOH/Iodof paste syringes. This procedure
standardized the material, and its insertion into the root
canals was facilitated. This fact was observed in an in vitro
study testing the filling capacity of different materials,8
as well as with the findings observed with the secondary
outcome of the present investigation. The quality of the
root canal filling with the experimental material stored in
syringes and the CaOH/Iodof paste was similar in both
studies, but the delivery system likely did not influence
the primary endpoint.
Based on the prototype studies and its efficacy, per re-
search conducted, this material could be manufactured
and introduced to the market. Nevertheless, to date no
company is producing the material. The success rate ob-
tained with this experimental material was non-­inferior
to the that achieved with the CaOH/Iodof filling mate-
rial, and success rates are similar to those obtained with
other materials.4,5,15 Yet, these findings were obtained
with the material manufactured and stored in syringes,
and all treatments were carried out by an experienced
clinician.
Consequently, the success rate presented could be
overestimated when compared to treatments conducted in
a real clinical scenario. When the material is handled by
clinicians at the time of treatment, variations in the mate-
rial's proportion and consistency are expected. Thus, low
success rates could be expected, limiting the generalizabil-
ity of the present findings. For the above, success rates
should be evaluated in more pragmatic trials to guarantee
the extrapolation of findings in daily clinical practice.
676 |    BRESOLIN et al

F I G U R E 2 Kaplan-­Meier curves comparing survival rates with respective 95% confidence intervals in primary teeth with endodontic
treatment filled with a calcium hydroxide and iodoform paste (the control group) and Guedes-­Pinto paste (the experimental group)

TABLE 3 Reasons for treatment failures CONFLICT OF INTEREST

The dental company Angelus does not have any com-
Reasons for treatment CaOH/Iodof paste GP paste
mercial interest in any materials used in the research.
failures N (%) N (%)
The University of São Paulo holds Brazilian patent for
Some clinical sign 4 (36.4) 2 (28.6)
the Guedes-­Pinto paste, and ACVM-­M and FMM are ap-
Some radiographic sign 2 (18.2) 2 (28.6) pointed as inventors. Other authors declare that they do
Restoration failure 5 (45.4) 3 (46.8) not have any conflict of interests.
Total 11 (100.0) 7 (100.0)
Note: All teeth presented with only one type of failure. ORCID
CaOH/Iodof, calcium hydroxide and iodoform paste (reference filling Renata P. S. Marques https://orcid.
material). org/0000-0002-3686-982X
GP, Guedes-­Pinto paste (experimental filling material). Juan S. Lara https://orcid.org/0000-0001-9434-4127
Fausto M. Mendes https://orcid.
Moreover, a direct comparison was made only with org/0000-0003-1711-4103
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